Main : General Hepatitis C News/Updates Archives

November 25, 2005

A Good AASLD Meeting Summary

This is a terrific overview article regarding the AASLD meeting. Liz Highleyman did a fantastic job of condensing the key aspects and announcements.

One of the most interesting updates/corrections of known information is the upward measurement of the number of infected persons in the USA. It could be one million more than most commonly estimated.

Hepatitis research reported at liver disease meeting

Liz Highleyman

Treatments for hepatitis B and C continue to improve, with refinements to approved regimens and new experimental agents in the development pipeline, researchers reported at the 56th annual meeting of the American Association for the Study of Liver Diseases, held November 11-15 in San Francisco.

Hepatitis B and C are viral diseases that can cause long-term liver damage including cirrhosis and cancer. The Centers for Disease Control and Prevention estimates that some 75,000 people in the U.S. are newly infected with hepatitis B each year – a number that has declined dramatically since the advent of routine childhood vaccination.

Unlike hepatitis A and B, there is not yet a vaccine for hepatitis C. The National Health and Nutrition Examination Survey found that about 3.9 million people in the U.S. had contracted hepatitis C, but Dr. Brian Edlin from Cornell University presented evidence suggesting this is an underestimate. As a household survey, Edlin said, NHANES does not count several groups that have higher rates of hepatitis C than the general population. These include prisoners (nearly 2 million, with an estimated hepatitis C rate of 32 percent), the homeless (more than 800,000, with an estimated rate of 35 percent), patients in hospitals and nursing homes, and members of the military. Taking these groups together, Edlin estimated that about 1 million more people have hepatitis C than usually reported, for a total of 5 million. Basing public health projections on the lower figure, he warned, "may underestimate the burden of liver disease we will see in coming decades."

Hepatitis C
The hepatitis C virus is spread primarily through contact with blood, and rates are highest among injection drug users. Several studies have shown that sexual transmission between monogamous heterosexual partners is rare, but it appears more common among men who have sex with men and people coinfected with HIV. While outbreaks of sexually transmitted hepatitis C have not been reported in North America, a cluster of more than 200 such cases among gay HIV-positive men in the United Kingdom raises concern.

According to a presentation by Dr. Mark Danta from the Royal Free and University College Medical School in London, a variety of factors related to sexual activity and drug use have contributed to the recent English epidemic. In a case-control study comparing 60 HIV-positive gay men with acute (recently acquired) hepatitis C and 130 matched HIV-positive men without HCV, Danta's team found that the HCV-infected men were significantly more likely to have engaged in unprotected receptive or insertive anal intercourse, fisting, analingus (rimming), use of sex toys, SM, and group sex. Further, the men with hepatitis C were more likely to meet partners in sex clubs, bathhouses, or on the Internet; had more sex partners overall; were more likely to have ever had a sexually transmitted disease; and more often used club drugs including crystal methamphetamine.

While all these factors are linked to higher rates of hepatitis C, Danta said it is "difficult to tease out" how each specifically contributes. He recommended that education about safe sex and drug-sharing practices should be the focus of public health interventions for this population.

At a satellite symposium, HIV specialist Dr. Paul Volberding from the University of California, San Francisco joined several hepatitis experts to discuss similarities and differences between the HIV and HCV viruses and their treatment. Research on hepatitis C is some five to 10 years behind HIV research, Volberding estimated. Hepatitis C researchers are at a disadvantage because HCV cannot be grown in the laboratory, which is important for understanding the virus life cycle and early drug testing (instead, various model systems are used). But patients with hepatitis C enjoy a big advantage: HCV can essentially be eradicated, while HIV persists indefinitely in long-lived memory T-cells.

Current standard treatment for hepatitis C is based on interferon, an injected cytokine (cell messenger chemical) that stimulates the immune response, but future therapies under study directly target HCV. Like current HIV drugs, these new agents will likely be used in combination, since HCV – like HIV – can mutate rapidly and develop drug resistance. But because hepatitis C can be cured in a matter of months or years, there is less concern about long-term side effects such as lipodystrophy.

"This field is getting very lively and will become even more competitive," predicted hepatology researcher Dr. John McHutchinson of Duke University Medical Center in North Carolina.

Indeed, researchers at AASLD presented data on several new candidate hepatitis C drugs. Those furthest along in the pipeline include Idenix Pharmaceuticals' nucleoside analog valopicitabine (NM283) and two HCV protease inhibitors, Shering Plough's SCH503034 and Vertex Pharmaceuticals' VX-950.

Presenting the first data from a phase II trial of valopicitabine, Dr. Christopher O'Brien from the University of Miami reported that 50 percent to 70 percent (depending on dose) of patients with genotype 1 HCV – the hardest type to treat – who did not respond to previous interferon therapy saw an early reduction in HCV viral load after 12 weeks of treatment with the new drug plus pegylated interferon.

"These are promising results, particularly for the many treatment-refractory patients in urgent need of new therapeutic options," O'Brien said.

Dr. Stefan Zeuzem from Germany reported that in a small 14-day study of patients who did not respond to standard treatment with interferon, 60 percent of those receiving the highest dose of SCH503034 three times daily experienced a substantial (at least two logs) reduction in HCV viral load. SCH503034 also showed promising activity when combined with pegylated interferon.

As reported by Dr. Henk Reesink from Amsterdam, in a small early study, all participants with genotype 1 HCV who received VX-950 saw at least a two-log drop in HCV viral load. "As far as I know, this is the most rapid and dramatic response that has been seen with a single agent," he stated.

All three pipeline drugs appear safe, with no serious side effects seen in clinical trials so far. This is reassuring since research on an earlier HCV protease inhibitor, BILN-2061, had to be stopped when it was linked to heart problems in animals. It is too soon to say whether these agents will ultimately produce a cure for hepatitis C (sustained virological response, or continued undetectable HCV viral load six months after the end of treatment). Most experts agree, however, that combinations of antiviral drugs are the wave of the future for hepatitis C therapy.

Posted by Ralph at 06:16 PM | Comments (0)

November 23, 2005

Shorter Therapy Effective for Genotypes 2 and 3

Genotypes 2 and 3 are much more responsive to current interferon combination therapies. This report details studies that show a shorter course of treatment might be just as effective as longer courses.

Researchers continue to refine treatment protocols for HCV patients.

Short Therapy Regimens Effective for Hepatitis C Virus Genotype 2 and 3: Presented at AASLD

By Crystal Phend

SAN FRANCISCO, CA -- November 21, 2005 -- Hepatitis C infected patients with genotype 2 or 3 may be able to shorten their course of therapy without losing effectiveness, according to a study presented here at the American Association for the Study of Liver Diseases annual meeting (AASLD).

According to presenter Olav Dalgard, MD, PhD, Infectious Diseases Specialist, Aker University Hospital, Oslo, Norway, the viral response at week 4 may be a guide to considering shorter treatment.

Two recently published studies found shorter therapy to be effective, but left unanswered which subgroups are less likely to respond, that is, dosing and baseline predictive factors, Dr. Dalgard said during a presentation on November 14th.

To answer those questions, his group used pooled data from two studies involving a total 403 adults with hepatitis C genotype 2 or 3 who were treatment naïve.

The Norwegian study dosed pegylated interferon alpha-2b at 1.5 mcg/kg once weekly with 800 to 1,200 mg of ribavirin for 14 weeks or for 24 weeks if patients had not achieved a response by week 14.

The Italian study followed the same schedule as the Norwegian study, with a slightly lower 1.0 mcg/kg pegylated interferon alpha-2b dose for 12 weeks or 24 weeks for non-responders at week 12.

Patients were tested for virus RNA levels at weeks 4, 12 or 14 and 24.

The 313 patients who achieved a sustained viral response (SVR) were analyzed by subgroup.

Results show a significant difference in the percentage of patients who achieved SVR according to fibrosis score ( 83% with a score of 0 to 2 vs. 67% with a score 3 to 4).

Patients with genotype 2 were significantly more likely to respond than those with genotype 3 (81% vs. 73%).

"In non-rapid viral response patients, 24 weeks of therapy for HCV 2 patients may be satisfactory whereas longer courses should be considered for genotype 3," Dr. Dalgard said.

Patients who had a rapid viral response by week 4 were significantly more likely to have a sustained viral response than those who did not (85% vs. 62%).

Those who had a rapid viral response at week 4 were significantly more likely to have a low fibrosis score (70% 0 to 2 vs. 56% 3 to 4) and to be at the higher 1.5 dose of peginterferon (78% vs. 64%).

Multivariate analysis found that the response at 4 weeks was a significant predictor of sustained response, although genotype, baseline viral load and treatment regimen were not.

Relapse could not be predicted by any baseline characteristic.

"In HCV 2 or 3, viral response at week 4 may reliably guide treatment duration as the majority of rapid responders may safely receive shorter courses of therapy without compromising SVR," the researchers concluded.

[Presentation title: Short-Term Treatment Duration for HCV-2 and HCV-3 Infected Patients with Chronic Hepatitis. Abstract 849]

Posted by Ralph at 01:10 AM | Comments (0)

November 16, 2005

Pegasys Shown More Effective In Study

Schering and Roche are taking part in dueling press releases.

Each claiming their solution is better. Either way, they seem to be splitting hairs regarding effectiveness.

There is no clear winner when they keep firing PR salvos back and forth. Who is a patient to believe? How do doctors determine what is best for their patients?

Be sure to stay informed and make as educated a choice as you can.

HEPATITIS C PATIENTS FARE BETTER WITH PEGASYS(R) - STUDY FROM POLAND SHOWS SIGNIFICANT DIFFERENCE IN EFFICACY BETWEEN LEADING TREATMENTS
15-11-2005 06:30

WARSAW, Poland, November 15 /PRNewswire/ -- Early results from a new study comparing the efficacy of the two leading hepatitis C treatments suggests that patients may increase their chance of a cure by more than 10% if they are treated with PEGASYS(R) and COPEGUS(R) combination therapy. The study, presented today at the 56th Annual Meeting of the American Association for the Study of Liver Diseases, is one of the first scientifically rigorous research efforts comparing leading treatments to determine which provides the best solution for patients battling hepatitis C [1].

"Patients and the medical community are understandably anxious to have reliable information regarding what treatment is most likely to provide a cure for hepatitis C," said Dr Andrzej Horban, from Infection Disease Hospital in Warsaw who headed the study. "My colleagues and I wished to undertake a study that would clearly answer this question and use a methodology that would inspire confidence in the results."

To date, there have been a number of comparative studies undertaken, but few if any, have generated results which reflect best practices in clinical research. In fact, a number of studies promoted to the public have been retrospective analyses of small research efforts that were designed to address different research questions altogether.

More PEGASYS Patients Respond After Only 12 Weeks of Treatment
The study was undertaken in Poland and involved more than 200 people infected with hepatitis C. All patients were assigned to be treated with either PEGASYS combination therapy or Peg Intron(R) combination therapy. After 12 weeks of treatment, 85% of the PEGASYS patients were responding to therapy as compared to only 74% of the Peg Intron patients. Response to therapy at 12 weeks (defined as either a significant drop in viral load or eliminating the virus completely) is typically an excellent indicator that a patient will be cured of the disease upon completing the full course of therapy.

Local Patient Groups Respond with Enthusiasm
Mr Jaroslaw Chojnacki - The chairman of the Prometeusze Community - said: "although we are still awaiting the final results of this study, the patient community is very pleased that this study has been undertaken in Poland. The results of this study can help infected people a lot. If we are convinced that someone's odds of beating this disease are increased by 10% because they took this drug, it would be important information for us", he said.

Like many countries in Europe, Poland is actively addressing the potential time bomb that is hepatitis C. Official figures state 1.5% of the population may have the virus. However patient groups and treating doctors believe that the figure is much higher.

Reference:
[1] Berak, H et al. "Randomized, Open Label Trial Comparing efficacy and safety of pegylated interferon alfa 2a vs 2b treatment of patients with chronic hepatitis infected with non 2/3 genetypes - 12 week virological response" Presented at AASLD, 2005.

Posted by Ralph at 08:03 AM | Comments (0)

November 15, 2005

Weight-based Treatment of HCV

Weight-based dosing has always made sense to us. We don't really understand why Roche has not changed their dosing to weight-based.

Although the difference is subtle, it is certainly significant according to this study.

You must also note, though, that Schering is funding this study. Does bias matter in science? What do you think?

Largest Hepatitis C Trial in U.S. Patients Shows Weight-Based REBETOL in Combination With PEG-INTRON Increases Sustained Response, Lowers Relapse

Final Results of Community-Based WIN-R Study Also Demonstrate Efficacy of Shorter, More Tolerable 24-Week Regimen in Patients With Genotype 2 or 3 Virus

SAN FRANCISCO, CA -- (MARKET WIRE) -- 11/14/2005 -- Final results of the WIN-R trial,(1) the largest hepatitis C study conducted in U.S. patients, showed that weight-based REBETOL® (ribavirin, USP) in combination therapy with PEG-INTRON® (peginterferon alfa-2b) achieved significantly higher rates of sustained virologic response (SVR)(2) and lower rates of relapse compared to the combination therapy using a flat dose of ribavirin. The study also showed that, for patients infected with hepatitis C virus (HCV) genotype 2 or 3, a shorter, 24-week course of therapy was as effective as the standard 48-week course, with better tolerability.

These results from WIN-R (Weight-Based Dosing of PEG-INTRON and REBETOL), a community-based access trial involving more than 4,900 patients at 225 centers across the United States, were reported in an oral presentation today at the 56th annual meeting of the American Association for the Study of Liver Diseases (AASLD).

"These findings help further define optimal therapy for U.S. hepatitis C patients treated in real-world community settings," said principal investigator Ira M. Jacobson, M.D., Vincent Astor Professor of Clinical Medicine at Weill Medical College of Cornell University and chief of the division of gastroenterology and hepatology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City.

Treating U.S. hepatitis C patients can be especially challenging as they tend to have disease characteristics that are associated with poor response to treatment, including high prevalence of HCV genotype 1, the most difficult type of the virus to treat; high viral load; and advanced liver fibrosis. Other factors such as age, high body weight and African-American ethnicity also have been shown to be associated with poor response.

"Our findings showed that the weight-based dosed combination therapy significantly increased efficacy compared to the flat-dosed ribavirin regimen, especially in more difficult-to-treat patient groups, such as patients with genotype 1 and African-American patients. This confirms what many treating physicians have come to know in their everyday practice and experience," Jacobson said. "Importantly, sustained virologic response rates in this community-based U.S. study were consistent with those seen in the U.S. cohorts of the earlier pivotal studies for the two approved peginterferon combination therapies."(3,4)

Study Design

In the WIN-R study, 4,913 patients were randomized to receive weight-based PEG-INTRON (1.5 mcg/kg weekly) in combination with REBETOL given either as a flat dose (800 mg daily) or a weight-based dose (800 mg, 1,000 mg, 1,200 mg or 1,400 mg daily for body weights of less than 65 kg, 65 to 85 kg, 86 to 105 kg, or 106 to 125 kg, respectively). Patients were treated for 48 weeks (genotype 1) or 24 weeks (genotype 2 or 3). Patients in the treatment arms were evenly matched for gender, age, body weight, genotype, viral load and stage of liver fibrosis.

Key Results

A challenge with conducting large community-based HCV studies such as WIN-R, as opposed to registration trials with their more intensive monitoring capabilities, is the tendency for a high rate of patients to miss their follow-up viral testing (PCR) visit 24 weeks after treatment ends due to the limited ability of many sites to conduct rigorous monitoring of patients once they have received their final treatment dose. In the WIN-R study, 13.1 percent (164/1,256) of patients in the weight-based dose group and 13.7 percent (163/1,193) of patients in the fixed-dose group who were responders at the end of treatment were lost to follow up and subsequently counted as treatment failures under a strict intent-to-treat (ITT) analysis.

Nonetheless, the WIN-R study showed significantly better outcomes for the weight-based combination regimen as compared to the flat-dosed ribavirin regimen, including:

-- Significantly higher SVR overall (44.3 percent vs. 40.6 percent,
p=0.01, ITT) and for patients with genotype 1 (34 percent vs. 29 percent,
p=0.004, ITT). These SVR rates are consistent with those seen in the U.S.
cohorts of the earlier pivotal studies for the two approved peginterferon
combination therapies.(3,4)

-- Using an estimated SVR analysis, based on results for patients who had
undetectable virus at the end of treatment and were subsequently lost to
follow up, SVR was 53 percent vs. 48 percent (p=0.008), respectively, for
the weight-based vs. flat-dosed ribavirin groups.

-- Consistent SVR rates were seen across all weight groups for patients
in the weight-based dosed regimen compared to the flat-dosed ribavirin
regimen where SVR rates declined in the higher weight groups, ranging from
52 percent to 34 percent. Consistent with other U.S. studies, patient
weight tended to be high in the WIN-R study, with 45 percent of patients
weighing 86 kg (189 lbs) or more.

-- For patients with HCV genotype 2 or 3 virus, a 24-week course of the
combination therapy was as effective as 48 weeks, with better tolerability.
In the weight-based dose arms, SVR was 68 percent for the 24-week course
compared to 60 percent for the 48-week course, with the lower percentage
attributable to more missing follow-up data.

-- Lower rates of relapse were seen for patients receiving the weight-
based combination therapy compared to the flat-dosed ribavirin regimen, 15
percent vs. 19 percent overall, and 23 percent vs. 29 percent for patients
with HCV genotype 1. Relapse is defined as patients with undetectable virus
levels at the end of treatment who subsequently had detectable virus at 24
weeks post-treatment.

-- Although there was a higher rate of anemia (hemoglobin < 10 gm/dl) in
the weight-based dosing group and more dose reductions (29 percent vs. 23
percent), no difference was seen in the rate of occurrence of serious
adverse events between the two groups (12 percent vs. 11 percent) and there
were similar rates of discontinuations for adverse events (15 percent vs.
14 percent).

WIN-R Study
Serving with Dr. Jacobson as co-principal investigator of the WIN-R study is Dr. Robert S. Brown Jr., associate professor of clinical medicine at Columbia University College of Physicians and Surgeons; and chief of clinical hepatology and medical director of the Center of Liver Disease and Transplantation at NewYork-Presbyterian Hospital/Columbia University Medical Center. Drs. Jacobson and Brown are also co-directors of NewYork-Presbyterian Healthcare System's Liver Clinical Trials Network (LCTN).

Dr. Jacobson also is medical director of the Center for the Study of Hepatitis C, a unique interdisciplinary center established jointly by The Rockefeller University, NewYork-Presbyterian Hospital and Weill Cornell Medical College in New York City.

WIN-R is an investigator-initiated clinical study supported by Schering-Plough Corporation and monitored by Schering-Plough Research Institute as part of a post-marketing commitment to the U.S. Food and Drug Administration (FDA). PEG-INTRON and REBETOL are registered trademarks of Schering-Plough.

About Hepatitis C

Hepatitis C is the most common blood-borne infection in America, affecting approximately 4 million people or about one in every 50 adults. Chronic hepatitis C can cause cirrhosis, liver failure and liver cancer. It has been estimated that at least 20 percent of patients with chronic hepatitis C develop cirrhosis, and a smaller percentage of patients with chronic disease develop liver cancer. Patients with chronic hepatitis C and related cirrhosis are 100 times more likely to develop liver cancer than uninfected persons.(5) About half of all cases of primary liver cancer in the developed world are caused by hepatitis C, and hepatitis C related liver disease is now the leading cause for liver transplants.(6)

About NewYork-Presbyterian Hospital/Weill Cornell Medical Center

The NewYork-Presbyterian Hospital/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian Hospital and its academic partner Weill Cornell Medical College. NewYork-Presbyterian/Weill Cornell provides state-of-the-art in-patient, ambulatory, and preventive care in all areas of medicine, and is committed to excellence in patient care, research, education, and community service.

References

1. Jacobson I, Brown Jr. R, Freilich B, Afdahl N, Kwo P, Santoro J, Becker S, Wakil A, Pound D, Godofsky E, Strauss R, Bernstein D, Flamm S, Bala N, Araya V, Davis M, Monsour H, Vierling J, Regenstein F, Balan V, Dragutsky M, Epstein M,. Herring RW, Rubin R, Galler G, Pauly MP, Griffel LH, Brass CA, the WIN-R Study Group. Weight based ribavirin dosing (WBD) increases sustained viral response (SVR) in patients with chronic hepatitis C (CHC): final results of the WIN-R study, a U.S. community-based trial. Oral presentation at: 56th Annual Meeting of the American Association for the Study of Liver Diseases, San Francisco, CA, Nov 11-15, 2005.

2. Sustained virologic response (SVR) is defined as undetectable virus (HCV-RNA) levels in the blood at 6 months after the end of therapy.

3. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep 22;358(9286):958-65.

4. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Haussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002 Sep 26;347(13):975-82.

5. Ince N, Wands JR. The increasing incidence of hepatocellular carcinoma. N Engl J Med 1999 March 11;340:10.

6. Centers for Disease Control and Prevention. Recommendations for prevention and treatment of hepatitis C virus (HCV) and HCV-related chronic disease. MMWR Weekly Report 1998 Oct. 16;1.

Posted by Ralph at 11:58 AM | Comments (0)

November 09, 2005

Your Results May Vary For HCV Treatment

According to this study, actual treatment results may be only half as good as touted. Doctors tend to trust the numbers presented by the pharaceutical companies. The pharmaceutical companies have a vested interest in presenting the best numbers they can find.

Patients may be unpleasantly surprised with the actual results.

Hepatitis C Often Untreated and Outcomes Lag behind Trials in Clinical Practice: Presented at ACG

By Paula Moyer

HONOLULU, HI -- November 9, 2005 -- When patients with hepatitis C go on antiviral therapy, the likelihood of a response may be half of that seen in clinical trials, according to investigators who presented their findings here at the 70th annual meeting of the American College of Gastroenterology (ACG).

The research was presented on November 2nd by Ramsey C. Cheung, MD, Chief of Hepatology, Veterans Affairs Palo Alto Health Care System, and Associate Professor of Medicine, Stanford University Medical School, Stanford, California, United States.

"A lot of people with a diagnosis of hepatitis C are not being treated for multiple reasons," Dr. Cheung, MD, said in an email. "When we decide to treat a patient and when the patient decides to go on treatment, the probability of achieving a cure is important to both parties."

However, he added, his study showed that the response rate is much lower in clinical practice than has been seen in the registration trial. "It is important for the treating physician and the patient to know what the response rate is likely to be, not what has been reported in registration trial."

He noted that studies of patients with hepatitis C within the Veterans Affairs system showed that the sustained viral response rate was low. The investigative team conducted the current study to see if the same results would be seen in a community cohort.

The team reviewed several databases of selected sites within the Kaiser Permanente Northern California Health System, and identified 1470 patients with chronic hepatitis C who were seen within the system from 1999-2004. They obtained demographic information from administrative files on age, gender, and ethnicity and patients' laboratory records.

The system's pharmacy records held data on patients' treatment with interferon combined with ribavirin or pegylated interferon combined with ribavirin, along with information regarding the patients' use of erythropoetin (Procrit), filgrastim (Neupogen), antidepressants, and transfusions.

Results show that 246 (16.5%) underwent treatment; 65.3% of these patients were men. Data were completely evaluable for 242 patients; 119 of these were treated with interferon plus ribavirin, and 123 were treated with pegylated interferon plus ribavirin. Patients were an average of 47.1 years old (range 33.3-60.91).

The vast majority of treated patients (72.4%) had HCV genotype I, while 24% had HCV genotypes II and III, and 3.6% had HCCV genotypes IV-VI.

Patients were treated for an average of 29.2 weeks. A sustained virologic response occurred in 19.8% of treated patients, including 11.8% of those who received interferon plus ribavirin, and 27.6% of those treated with pegylated interferon plus ribavirin.

In clinical trials, sustained viral response rates have reached more than 70%, Dr. Cheung said.

Although the reasons for the gap are unclear, these findings may help physicians and patients have more realistic expectations of treatment, Dr. Cheung said.

[Presentation title: Practice Patterns and Treatment of Outcomes in the Management of Chronic Hepatitis C (CHC) Infection in a Large Managed Care Cohort. Abstract 785]

Posted by Ralph at 05:09 AM | Comments (0)

October 26, 2005

More HCV Treatment News Coverage

The Los Angeles Times is one of the largest daily newspapers in the U.S. Their interest in HCV is indicative of a growing awareness of the extent of the disease in this country.

The article clearly focuses on the hope of safer, more effective treatments than what is now available.

Science & Medicine | Los Angeles Times Examines Study Results of Three Experimental Hepatitis C Treatments

[Oct 25, 2005]

More than 24 hepatitis C treatments currently are in development, and at least three drugs are demonstrating the potential to prevent the virus from replicating, the Los Angeles Times reports. "These drugs are more potent and have much less side effects" than treatments that currently are available, Eugene Schiff, director of the Center for Liver Diseases at the University of Miami, said.

One drug, called valopicitabine -- which is manufactured by Cambridge, Mass.-based Idenix Pharmaceuticals and is currently in more advanced clinical trials than other experimental hepatitis C therapies -- works by blocking the action of RNA polymerase, an enzyme the virus needs to replicate. In a study of 79 patients conducted last year, the once-a-day pill reduced hepatitis C viral levels by up to 90% after two weeks of treatment, even though 87% of the trial's participants had received previous treatments that failed to reduce their viral loads. The interim results of another valopicitabine trial -- which involved 190 hepatitis C patients not helped by conventional treatment regimens -- are scheduled to be released in November. Preliminary results of that trial show a decrease in viral reproduction, according to the Times. Nathaniel Brown, chief medical officer at Idenix, said that valopicitabine likely will be part of a combination therapy, "but we're in a race against time because the number of people with advanced disease is steadily increasing."

Two other experimental hepatitis C drugs recently have completed early stage clinical trials: SCH-503034, made by Schering-Plough, and VX-950, made by Cambridge, Mass.-based Vertex. Both treatments target the protease enzyme, which the virus uses to reproduce. Results from a Shering study on SCH-503034 are expected to be released in November, and Shering liver expert Janice Albrecht said that the decrease in viral levels was "significant." A study conducted this year of VX-950 involving 34 volunteers showed that after two weeks of treatment, the medication proved 250 times as powerful as conventional medication in reducing hepatitis C levels. Researchers are planning additional studies for both drugs (Marsa, Los Angeles Times, 10/24).

Posted by Ralph at 09:57 AM | Comments (0)

September 29, 2005

A Good HCV Newspaper Article

This is one of the best general audience articles we've come across on HCV in quite a while. There is lots of good info on treatment. Notice that even the doctor says the "cure" rate has only risen to about 50% (and that includes the over 80% for genotype 2) This indicates that, in real numbers, it is even lower than 50% for Genotype 1 patients.

Dr. Goddofsky says he was encouraged about Tarvacin because it has low toxicity.

Clearly, this is the sort of treatment we are waiting for. We're just protecting and supporting our liver as best we can (through natural means) in the meantime.

For more info on how to protect and support your liver (if you aren't already aware) you can go to http://www.liversupport.com/interview.htm

Bradenton doctor chips away at hepatitis C virus
Medical office runs 10 to 20 drug trials a year

By KATHLEEN MCLAUGHLIN

kathleen.mclaughlin@heraldtribune.com

BRADENTON — When Eliot Godofsky started treating viral hepatitis in 1996, about 10 percent to 15 percent of patients could be cured.

After the introduction of some new drugs, that rate is up to 50 percent.

Godofsky likes those numbers, but he knows they could be even better. “HIV is controllable. Hep-C is potentially curable.”

That’s why his Bradenton-based medical office — the nation’s largest infectious disease practice specializing in viral hepatitis — runs 10 to 20 drug trials a year.

Private practice physicians get involved in clinical research for many reasons: money, experience with cutting-edge treatment, access to drugs for patients.

Godofsky says his prime motivator is fundamental: “The benefit to me is to cure people who thought they were incurable.”

The 46-year-old came to Bradenton to join Michael Bach, a pioneer in HIV/AIDS treatment who died of melanoma in 1998.

Bach & Godofsky, M.D. PA, which now employs six other doctors, still staffs the HIV/AIDS clinic that Bach opened in Manatee County. But Godofsky has expanded the scope of the practice and become an expert on viral hepatitis. Part of that includes doing early-stage drug trials, such as the one for Peregrine Pharmaceuticals that began Aug. 29.

He hopes to help find something that will work for the roughly 50 percent of people who don’t respond to treatment, which involves a yearlong course with debilitating side effects.

The virus

The hepatitis C virus is more widespread than HIV, but it gets relatively little attention.

About 4 million people in the United States are infected with hepatitis C, while about 1 million have HIV.

No national fund like the one established by the Ryan White CARE Act for HIV pays for hepatitis drugs. Treatment, not including lab work, costs about $20,000 per year, Godofsky said.

There are a lot of drugs under research for hepatitis C, but there is not a high-profile, independent center testing them head-to-head, said Lisa Ball, executive director of the Hepatitis Resource Network, a doctors education group.

Sharing needles is the most common cause forof the illness, representing 60 percent of new infections. Although commonly associated with illegal drug use, hepatitis crops up unexpectedly in many middle-aged people because the disease can stay in the body for 10 to 20 years without causing anything more than flu-like symptoms, said Michelle May, the nurse practitioner who runs clinical trials for Godofsky.

Some patients trace their risk back to recreational cocaine use, in which they shared straws, May said.

One woman’s only identifiable risk factor was the fact that she was a seamstress. She might have pricked her finger on a needle used by someone else.

A lot of people don’t realize they can be cured. Some go through the treatment, only to find themselves among the “non-responders.”

“The worst part of my job is helping them through 12 months of therapy, then six months later having to call and say, ‘Your virus is back,’” May said.

There are 12 to 15 companies trying to develop new drugs, and many of them contact Godofsky’s office for trials.

Godofsky thought Peregrine’s drug, Tarvacin, looked promising. The small California company realized the antibody treatment it was developing for cancer tumors might work against hepatitis and other viruses.

The Bradenton doctor agreed to the trial because the drug seems to have low toxicity, and it’s a novel approach: Patients will get one intravenous injection of the antibody, which might block the virus from invading liver cells and remove the virus from the body.

Supporting treatment

Godofsky was drawn to research as an intellectual pursuit, but he has become an expert on the ins and outs of using it to support the practice. He gave a presentation on it last year at the annual meeting of the Infectious Diseases Society of America.

Listed among the reasons for doctors to get involved in trials was “cost-effective income production.”

The medical office gets “good” reimbursement for patient visits and lab reviews with limited billing and collections overhead. Doctors spend no time with managed care, Godofsky notes.

One of his tips on setting up a budget for a clinical trial was “do not be afraid to negotiate.”

“Physicians are not usually terrific businessmen,” but can be, Godofsky says.

Research is not a profit center, Godofsky acknowledges, but by using it he can support the staff required to care for the disease.

Treating viral hepatitis requires a lot of patient monitoring and education.

It can also be very complicated. About 10 percent of viral hepatitis sufferers also have HIV. Doctors know little about how the drugs used to treat the two viruses separately might interact.

Making a living at that kind of medicine is difficult, said Ball, the executive director of the Puyallup, Wash.-based Hepatitis Resource Network.

“There’s no procedure, so it’s not particularly well-reimbursed,” she said. “But patients have lots of questions.”

Many doctors don’t want to be involved.

Godofsky is on the board of directors of the organization, which was started in 1997 to raise awareness of hepatitis C among physicians.

Infectious disease doctors proved to be more interested in the disease than liver or intestinal doctors, Ball said. They are used to dealing with trying to get paid for the time they spend consulting, and many, like Godofsky, do it for the intellectual challenge.

Bach is what brought Godofsky to Bradenton: “He had that zest or lust for research.”

After his partner died, Godofsky said, he worked seven days a week, 20 hours each day for the subsequent year and a half. “I kept the research going. I kept the HIV care going. I gradually added more and more doctors.”

Now the seven doctors, including Godofsky, cover the three hospitals in Manatee County and the Michael Bach Treatment Center. They also work with Infectious Disease Associates of Sarasota.

Bach and Godofsky also runs a wound care center and a large outpatient IV clinic. The IV clinic, which is open every day, sees 80 to 100 people each day.

Godofsky estimates that he has a patient base of about 1,000 and that he accepts about 300 new patients a year.

Patients

May, the nurse practitioner who runs trials for Godofsky, does not have to recruit patients, even for early phase trials where the focus is on establishing safe doses, not treatment.

“They clamor to do these phase-one trials,” she said. “They want to make something good out of something bad.”

Fort Lauderdale resident Philip Younger is the kind of patient who would benefit from a breakthrough drug. He’s among the 50 percent who didn’t respond to treatment, even after three courses.

The 56-year-old was diagnosed with the disease in 2000 and soon started treatment: three shots a week of one drug, interferon, and six pills a day of another, ribavirin.

Younger, hurt on his job moving furniture, took work as as telemarketer to accommodate the side effects: headaches, fever, muscle aches and loss of appetite. He went on three medications to counteract the insomnia and depression.

During that time, Schering-Plough came out with an improved drug,he tried that, too. Younger went through 15 months of treatment, but the virus came back six months after the treatment ended.

Younger tried another company’s drug. That didn’t work, either.

“It’s a freaky virus,” he said.

Younger, who now works for a patient advocacy group called Hep-C Alert, said the treatment at least bought time for his liver, which showed no cirrhosis in his latest biopsy.

“I live right, eat right, hope for the best and counsel people on hepatitis,” he said.

Younger said that if he could take the time off work, he would join a trial now.

“I’ve always said I would shoot toothpaste if it would get rid of this virus,” he said.

Posted by Ralph at 12:38 PM | Comments (0)

September 02, 2005

Report Claims MOST HCV Patients Will Develop Cirrhosis

This is one of the most broad announcements regarding Hepatitis c I've seen in a long time. It appears to apply to all Hepatitis c patients.

And, while it seems to predict eventual doom and gloom for most HCV patients, it does so on a very shaky foundation.

And, oh boy,I've got a bit to say about the study this article refers to. Here is the actual conclusion of the study authors:

The prevalence of cirrhosis in patients with chronic HCV increases with increasing duration of infection. In Asian patients infected at birth, infection for over 60 years causes cirrhosis in 71% of infected individuals. Because relationship between the severity of fibrosis and age in Asian patients is similar to that seen in Caucasian patients it is likely that similar rates of cirrhosis will be seen in other patients who are infected for more than 60 years.

First of all, there is no mention of what genotype the "Asian" patients were infected with. According to data I have seen each genotype seems to progress at different rates and with differing levels of severity. 70% of North Americans have genotype 1. And Genotype 1b seems to progress differently than even 1a. And, in Asia, genotype 6 is fairly common. So, does the finding of this study really apply to genotype 1 (or 70% of Americans)?

The study also does not mention mode of infection, and other studies show there is a big difference in progression between those who were infected through transfusion and those infected through other means.

The broad conclusion of this study is that most HCV patients (up to 80%)will progress to cirrhosis after 60 to 80 years of chronic infection. Of course, this conclusion is drawn without taking into account certain variables (as mentioned above).

The actual report from Clinical Gastroenterology and Hepatology goes on to say this about one aspect of the study:

The authors also assumed that the Asian patients were infected at a very young age, largely on the basis of extrapolation of regression lines down to an age in which patients would presumably not have had fibrosis. This conclusion is speculative and goes well beyond the data presented in the study.

The study authors concluded that the majority of patients will progress to cirrhosis after 60 years. The Journal goes on to say this:

Such conclusions are currently premature. Specifically, additional studies are needed in other patient populations that overcome the design limitations of the current study and to address the alternative interpretation of the data that, although during a lifetime there might indeed be progression to cirrhosis, this might only seldom result in end-stage liver disease or the development of HCC.

So, while this looks pretty bad at first glance, closer scrutiny helps put it in clearer perspective.

Oh, one more thing. Most Americans were infected in their early 20's. 60 to 80 years puts them into their 80s to over 100. Hmmm, with an average life expectancy in this country of 72, it seems like HCV patients may do even better than average (wink).

Just shows you've got to take these preliminary study conclusions with a grain of salt. (By the way, be sure you note who helped sponsor this study. The info is near the bottom.)

----------------------------------------------------------------------

Public release date: 1-Sep-2005

American Gastroenterological Association

Most chronic hepatitis C sufferers will develop cirrhosis in later life

Study suggests cirrhosis and liver disease nearly inevitable for people with hep C

Bethesda, Maryland (Sept. 1, 2005) – Nearly 80 percent of chronic hepatitis C sufferers who have the disease for several decades will develop cirrhosis or end-stage liver disease later in life, according to a study published today in the American Gastroenterological Association (AGA) journal Clinical Gastroenterology and Hepatology. Researchers found that it is highly likely that people who are infected with hepatitis C (HCV) for more than 60 years will develop cirrhosis--the highest rate of hepatitis C-associated cirrhosis reported to date.

Hepatitis C is a virus that affects the liver and is spread primarily by contact with blood and blood products in transfusions and among drug users who share needles. Other common routes of transmission are infants born to HCV-infected mothers, tattoos and body piercings and risky sexual behavior. Of those who are infected, more than 80 percent will be chronic carriers of the disease.

HCV can cause long-term scarring of the liver and usually presents with mild and non-specific symptoms, if any. They include fatigue, nausea, poor appetite and muscle and joint pain. It is estimated that more than 4 million Americans are now infected with HCV (more than 170 million people worldwide) and nearly 10,000 Americans die from the disease each year.

"Hepatitis C begins generally as a silent acute infection, with a fraction of the patients developing cirrhosis, end-stage liver disease or liver cancer," according to an editorial appearing in this month's journal. "Although this is a generally accepted scenario in persons infected with HCV, there remains uncertainty about the true frequency of evolution of liver disease and its rate of progression."

According to results of the study from researchers at the Queen Mary's School of Medicine and Dentistry in London, the prevalence of cirrhosis in patients with chronic HCV increases with the duration of the disease. Nearly 80 percent of Asian patients who were infected at birth and lived with the disease for 60 years or more developed cirrhosis--a finding that researchers say can be applied to the general population because of the similarity in the way the disease progresses in all ethnic groups.

"This study suggests that prolonged infection with hepatitis C leads to cirrhosis in the majority of those who are infected," said Graham R. Foster, PhD, FRCP, study author and professor of hepatology at Queen Mary's School of Medicine and Dentistry in London. "While previous studies have found differences in disease progression in various ethnic groups, our findings confirm that fibrosis progression is the same across these groups and leads to development of cirrhosis and liver disease at the same rate in everyone."

Researchers conducted retrospective analyses of 382 patients diagnosed with hepatitis C at three hospitals in northeast London between 1992 and 2003. Study participants were divided into two groups: Asian patients presumably infected in childhood and Caucasian patients. While the prevalence of cirrhosis in Caucasian patients was similar to the findings of previous studies, the statistics in Asians were markedly higher than previously found. The higher prevalence was partially attributed to the longer duration of HCV in the Asian patient population, those patients having suffered with the disease nearly 30 years more than the Caucasian subjects.

###
This study was funded by local investigators and an unrestricted research grant from Roche Pharmaceuticals.

About the AGA
The American Gastroenterological Association (AGA) is dedicated to the mission of advancing the science and practice of gastroenterology. Founded in 1897, the AGA is the oldest medical-specialty society in the United States. The AGA's 14,500 members include physicians and scientists who research, diagnose and treat disorders of the gastrointestinal tract and liver. On a monthly basis, the AGA publishes two highly respected journals, Gastroenterology and Clinical Gastroenterology and Hepatology. The AGA's annual meeting is Digestive Disease Week®, which is held each May and is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.

About Clinical Gastroenterology and Hepatology
The mission of Clinical Gastroenterology and Hepatology is to provide readers with a broad spectrum of themes in clinical gastroenterology and hepatology. This monthly peer-reviewed journal includes original articles as well as scholarly reviews, with the goal that all articles published will be immediately relevant to the practice of gastroenterology and hepatology. For more information, visit www.cghjournal.org.

Posted by Ralph at 12:13 PM | Comments (1)

August 26, 2005

Hepatitis A Vaccinations Highly Recommended

If you are a Hepatitis c patient and have not yet been vaccinated against Hepatitis a, you should be as soon as possible. The story below helps to underline this fact.

While Hepatitis a is not normally deadly for most people, when contracted in HCV patients it has a much higher chance of killing them.

Don't delay. There is really no downside risk to getting the vaccination, and you could be risking your life unnecessarily otherwise.

Hepatitis A vaccine not widely used for Hepatitis C patients

25 Aug 2005

A new study examining whether patients with chronic Hepatitis C virus (HCV) were routinely vaccinated against Hepatitis A virus (HAV) found that vaccination rates were low, even though HAV vaccination is recommended for patients with chronic liver disease.

The results of this study appear in the September 2005 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). Published by John Wiley & Sons, Inc., Hepatology is available online via Wiley InterScience at interscience.wiley.com/journal/hepatology.

The HAV vaccine has been available since 1995, yet HAV infection continues to be one of the most preventable illnesses in the United States. It can cause severe liver disease, liver failure, and even death in patients who already have chronic liver disease. HAV vaccination was recommended for these patients by the 1996 Advisory Committee on Immunization Practices and numerous other health agencies, but it is not known to what extent it is being carried out.

Researchers led by Edmund J. Bini, M.D., M.P.H of the New York University School of Medicine identified 1,193 patients from January to December 2000 at the Veterans Affairs New York Harbor Healthcare System in New York who had chronic HCV infection. Follow-up information was collected through June 30, 2002 to determine the number of patients who were tested for HAV and the number who actually received the HAV vaccine. Patients were considered to be vaccinated if they received at least one dose of the vaccine. The study also examined the number of vaccine doses received, the proportion of patients who were susceptible to HAV among those tested (indicated by a negative HAV antibody result), the incidence of HAV infection during follow-up and the number of visits patients made to their primary care provider.

The results showed that 53.6 percent of the 1,193 patients had antibody testing performed, and almost half of these were susceptible to HAV infection. Yet only 94 patients received the HAV vaccine and of these, 45 received only 1 dose. Among the 94 patients who received the vaccine, 88 had been tested for HAV antibody. A total of 3 patients with HCV infection developed acute HAV infection, one of whom died of liver failure. All of them were known to be susceptible to HAV, but none had received the vaccine.

"The low rates of HAV testing and vaccination are striking given the presence of recommendations to vaccinate these individuals against HAV since 1996, the long duration of follow-up, and the high number of visits with their primary care provider," the authors state. "These findings have substantial public health implications and represent missed opportunities for prevention."

The authors speculate that the reasons for the low vaccination rates could include patient refusal (such as a belief that patients weren't at risk for HAV infection, doubts about the vaccine's effectiveness, or misconceptions about side effects), a lack of knowledge on the part of health care providers, a lack of resources, or because of a greater need to address more pressing health issues during medical visits.

The authors conclude: "Public health efforts at raising awareness about HAV vaccination in patients with chronic liver disease should be strongly encouraged. In addition, further studies to evaluate patient and provider barriers to HAV vaccination are needed to prevent future missed opportunities for vaccination."

Article: "Susceptibility to Hepatitis A in Patients with Chronic Liver Disease Due to Hepatitis C Virus Infection: Missed Opportunities for Vaccination," Michael Shim, Inessa Khaykis, James Park, Edmund Bini, Hepatology; September 2005; (DOI: 10.1002/hep.20830).

Posted by Ralph at 10:02 AM | Comments (0)

August 04, 2005

HCV Treatment and Obesity

This article contains quite a few tidbits of good information (in addition to the primary focus). The description of "signs" that a small number of patients have does a good job of covering possible symptoms and effects of the disease.

It also seems that the main difference in success between Pegasys and Peg-Intron in these patients may have more to do with the difference in dosing between standard levels of medication and weight based dosing.

PEG-Intron Shows Higher Sustained Responses in Obese Patients

by John C. Martin
Article Date: 08-03-05

A small observational study from the Cleveland Clinic is suggesting that the hepatitis C treatment PEG-Intron (peginterferon alfa-2b) helps obese patients with the viral infection achieve sustained therapy responses better than its competitor product, Pegasys (peginterferon alfa-2a).1

The results of the preliminary trial were released at Digestive Disease Week, an annual gastroenterology conference, held this year in Chicago.

Interferon/Ribavirin: The 'Gold Standard'
According to estimates, nearly 4 million Americans are infected with hepatitis C. Three-quarters of this population go on to become chronically infected, and most have accompanying chronic liver disease. HCV accounts for about 15% of acute viral hepatitis, up to 70% of chronic hepatitis cases, and half of all cases of cirrhosis, end-stage liver disease, and liver cancer. The disease is transmitted primarily through contact with blood or blood products, and the "gold standard" treatment at this point includes the combination of a pegylated, or longer-lasting, interferon combined with ribavirin.2

Symptoms of HCV may be absent, but in some cases may include the following:

• Fatigue
• Mild discomfort or tenderness on your upper right side
• Nausea
• Poor appetite
• Muscle and joint pains

A small number of people with the infection develop certain signs, such as skin rashes, kidney disease, neuropathy, cyroglobulins (abnormal blood proteins), rheumatoid factor (an abnormally produced autoantibody that reacts against immunoglobulins in the blood), and low levels of complement (proteins) in the blood.2

PEG-Intron (peginterferon alfa-2b), manufactured by Schering-Plough Pharmaceuticals, is a form of pegylated, or longer-lasting, interferon for hepatitis C. It is prescribed alone or in combination with an oral antiviral medication called ribavirin for adults with the disease. Another pegylated interferon, Pegasys (peginterferon alfa-2a), manufactured by Hoffman-LaRoche Pharmaceuticals, is also combined with ribavirin as a treatment for hepatitis C. Both PEG-Intron and Pegasys, manufactured by Hoffman-LaRoche Pharmaceuticals, are injectable medications used as therapy for hepatitis C.

Sustained Treatment Responses Compared
Doctors in the study compared sustained virologic responses (SVR) in people classified as obese with those considered non-obese using both medications. SVR is defined as continual non-detectable levels of the hepatitis virus for a minimum of six months after therapy ends.3 "Obese patients with hepatitis C virus (HCV) may have more rapid progression of liver disease and lower rates of response to antiviral therapy than nonobese patients," wrote the study's lead investigator, Nizar Zein, MD, in the department of Gastroenterology and Hepatology at the Cleveland Clinic, and his associates.

Thus, the investigators wanted to determine if either Pegasys or PEG-Intron, both combined with the oral antiviral drug, ribavirin, could help their obese patients achieve an SVR.

Study Participant Characteristics
Through a record search, Zein and his group identified nearly 100 patients who had arrived at the Cleveland Clinic between 2001 and 2004 for treatment of their hepatitis C. None of the patients had received treatment prior to their arrival. Each of the patients was infected with genotype 1 HCV, the most common and most difficult to treat strain of the virus.

Thirty-five patients were classified as obese, and the remaining 61 patients were designated non-obese. Each had undergone a biopsy before therapy to determine the health of their livers.

The researchers reported no significant differences in disease characteristics like liver enzyme levels or levels of HCV RNA, the virus' genetic material that doctors look for as an indicator of its presence. Forty percent of the obese patients had steatosis, or fatty liver, compared with just 16 percent of those classified as non-obese. "But frequency of advanced fibrosis or marked inflammation were not significantly different" between the two groups, Zein and his team wrote.

Which Medication Had Better Outcomes?
When analyzing which patients taking Pegasys in combination with ribavirin had achieved an SVR, the researchers found that two of eleven obese patients in this group (18 percent) did so, compared to eight of 29 non-obese patients (28 percent). By contrast, of those in the group taking PEG-Intron combined with ribavirin, nine of 17 obese patients (52 percent) and 14 of 29 non-obese patients (48 percent) similarly achieved a sustained response, the investigators found.

"Mild fibrosis, lower pretreatment HCV RNA, and weight-based dosing were independently associated with attainment of SVR," wrote the study team. In this research, weight-based doses of PEG-Intron were given to the patients compared with standard dosing using Pegasys. That means people taking PEG-Intron are assigned a specific dose based on their individual weight, as opposed to a standard dose that everyone taking Pegasys receives.

"Obese and non-obese patients have equal SVR when treated with weight-based doses of [peginterferon alfa-2b] in combination with ribavirin," wrote Zein and his group in conclusion. "However, when treated with standard-dosed [peginterferon alfa-2a] and ribavirin, obese patients are less likely to attain SVR."

So far, no formal clinical trials have been published comparing the efficacy of PEG-Intron versus Pegasys. However, Schering is sponsoring such a trial whose results will reportedly be released in 2007.

1. Cesario K, Khandwala F, Edwards K, Carey W, Barnes D, Zein N. Impact of obesity on degree of liver disease and response to therapy in patients with chronic hepatitis C genotype 1 infection. Digestive Disease Week 2005. 2005 May 14-19. Chicago, IL.
2. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). National Institutes of Health. Chronic Hepatitis C: Current Disease Management. Available at: http://digestive.niddk.nih.gov/
ddiseases/pubs/chronichepc/index.htm. Accessed July 28, 2005.
3. Fried MW, Shiffman ML, Reddy KR et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002 Sep 26;347(13):975-82.

Posted by Ralph at 07:25 AM | Comments (1)

July 26, 2005

HCV Treatment Clincal Trial Announcement

Another new treatment being tested against Hepatitis c. The drug companies are scrambling to get a better treatment to market than what is currently available. God bless them!

lobeImmune Initiates Phase 1b Study of GI-5005 for Chronic Hepatitis C Infection

DENVER, July 26 /PRNewswire/ -- GlobeImmune, Inc., a biopharmaceutical company that discovers, develops and manufactures immunotherapeutic products known as Tarmogens(TM) to treat cancer and infectious disease, today announced that it has initiated a Phase 1b study of GI-5005, a Tarmogen for the treatment of chronic hepatitis C infection (HCV). This study is being conducted under an Investigational New Drug application (IND) that was filed with the U.S. Food and Drug Administration in March 2005.

The Phase 1b study is a double-blind, placebo controlled, dose-escalation, multi-center trial evaluating the safety, immunogenicity, and efficacy of GI- 5005, a Tarmogen expressing a NS3-Core fusion protein. NS3 and Core are HCV protein antigens that are expressed in infected cells and are essential for virus replication. GI-5005 has demonstrated robust activity in preclinical models of HCV. Because Tarmogens elicit a balanced immune response that is similar to the response occurring in the minority of individuals who successfully clear primary hepatitis C infection, the Company believes that the GI-5005 Tarmogen may represent a successful approach to treating this difficult disease.

"Hepatitis C is an area of major unmet medical need," said Timothy C. Rodell, M.D., CEO of GlobeImmune. "We are hopeful that GI-5005 will ultimately be able to treat the significant proportion of patients for whom there is currently no effective therapy. This is a significant event for GlobeImmune, as this milestone represents the second Tarmogen product to enter human clinical trials in 18 months and the first clinical trial of a Tarmogen for the treatment of an infectious disease."

Chronic hepatitis C infection, a viral liver disease, is a global health epidemic. Currently, there are approximately 170 million people worldwide who are infected with the hepatitis C virus. Of these, 4-5 million live in the United States with an additional 5 million living in Western Europe. Approximately 20-30% of all hepatitis C patients will face life threatening complications as a result of their disease. Hepatitis C accounts for 20% of cases of acute hepatitis, 70% of cases of chronic hepatitis, 40% of cases of end-stage cirrhosis, 60% of cases of hepatocellular carcinoma (liver cancer) and 30% of liver transplants in the United States.

The incidence of new symptomatic infections with hepatitis C has been estimated to be 13 cases/100,000 persons annually. For every one person that is infected with the AIDS virus, there are more than four infected with hepatitis C. The Centers for Disease Control Prevention (CDC) estimate that there are up to 230,000 new hepatitis C infections in the United States every year. Currently, 8,000 to 10,000 deaths each year are attributed to the disease.

ABOUT GLOBEIMMUNE

GlobeImmune, Inc., is an emerging biopharmaceutical company pioneering the discovery, development and manufacturing of potent, targeted molecular immunotherapies called Tarmogens for the treatment of cancer and infectious diseases. The Company's lead products are in Phase 1 testing for the treatment of hepatitis C infection and for the treatment of cancers of the lung and gastrointestinal tract. Tarmogens are whole, heat-killed recombinant Saccharomyces cerevisiae yeast genetically modified to express one or more protein antigens that stimulate the immune system against diseased cells.

Posted by Ralph at 07:51 PM | Comments (1)

June 22, 2005

Shorter HCV Treatment? Yes, for some...

Because genotypes 2 and 3 respond so well to interferon therapy, researchers are studying how little they can give and still have a positive effect.

This is great for 30% of North Americans who have chronic Hepatitis c. But the rest of us are still looking at a year of treatment and maybe a 50% chance of success (at best).

Actually, I look at articles like this as much for secondary information as primary. For instance, I hadn't realized that only 5% of Americans have type 2. Wow! This means the best resonse to interferon can only be acheived by 5% of us.

Shorter Hepatitis C Treatment Works for Some
For Those With Hepatitis Type 2 or 3, 3-Month Treatment May Suffice
By Daniel DeNoon

WebMD Medical News

Reviewed By Michael Smith, MD
on Wednesday, June 22, 2005

June 22, 2005 -- Some people with hepatitis C may get by with only three months of treatment, an Italian study shows.

The findings apply only to people infected with type 2 or type 3 hepatitis C virus. They do not apply to people infected with the more common type 1 virus. In the U.S., about 70% of hepatitis C infections are type 1, about 5% are type 2, and about 20% are type 3.

Treatment for hepatitis C isn't easy. The drugs of choice are a once-a-week form of interferon alpha (peg-interferon) plus ribavirin, an antiviral drug. The side effects -- including flu-like symptoms, fatigue, and depression -- can be very hard to handle.

Current guidelines call for six months of treatment for hepatitis C type 2 and type 3 infections. A year of treatment is needed for type 1 infections.

But Alessandra Mangia, MD, of Casa Sollielo della Sofferenza Hospital, in San Giovanni Rotondo, Italy, and colleagues report that some patients with hepatitis C type 2 or type 3 infections may be able to cut their treatment time in half.

Fast Response, Shorter Treatment?

The goal of hepatitis C treatment is what doctors call a sustained virologic response. That's when the hepatitis C virus can no longer be detected in the blood. Many experts call this a cure; others are more cautious. Whatever it's called, patients with sustained virologic responses to treatment almost never see their hepatitis C infection come back to dangerous levels.

Side effects force some patients to quit treatment early. Usually, that means treatment failure; usually -- but not always.

"We saw that a few patients, who withdrew from therapy before the standard six-month period, had sustained virologic responses anyway despite their short course of treatment," Mangia tells WebMD. "And we saw that some patients show a very fast reduction of hepatitis C virus levels after their first interferon treatment."

Did early response to treatment predict who would do well with short-term therapy? The researchers designed an experiment. They enrolled 283 people with hepatitis type 2 or type 3 infection. Seventy of the patients got the full six months of peg-interferon plus ribavirin. The other 213 patients started with the same treatment. If, after four weeks, their blood levels of hepatitis C virus became undetectable, these "fast responders" got only three months of treatment -- called variable-length treatment.

Mangia and colleagues report their findings in the June 23 issue of The New England Journal of Medicine.

What happened?

The researchers had good news for patients with hepatitis C type 2 or 3 that had no evidence of the virus after four weeks of treatment. "Patients treated for 12 weeks were spared the expense and inconvenience of extended treatment and still had a high response rate."

Too Good to Be True?

The response rates were similar between those treated for three months and those treated for six months. Overall, 76% of patients getting standard treatment and 77% of patients getting the variable-length treatment had a sustained virologic response.

But there were some differences.

At first, early responders -- those who had undetectable levels of hepatitis C virus after four weeks of treatment -- looked the same in both the standard and variable treatment groups. Ninety-three percent of early responders treated for six months and 95% of those treated for three months still had no detectable virus at the end of treatment. Six months later, that percentage dropped from 93% to 91% in those treated for six months. But it dropped from 95% to 85% in those treated for three months.

Although it sounds like the variable-length group have more viral "rebound," Mangia notes that the results were very similar between the two groups. And of the 13 patients who rebounded after three months of treatment, 10 agreed to 24 more weeks of treatment. This second course of treatment was successful for nine of these 10 rebounders.

"Only this small number of persons rebounded, without any major side effects, and without any reduction in the response rate for [further] treatment," Mangia says.

But these numbers worry hepatitis C expert Robert Fontana, MD, associate professor of medicine and medical director for liver transplant at the University of Michigan in Ann Arbor.

"Is this really an efficient way to manage patients? If you are going to go through this therapy, you would rather get rid of the virus," Fontana tells WebMD. "Yes, you have less of the side effects with 12 vs. 24 weeks of treatment. But if someone is tolerating it well, why risk the relapse? Plus there is the whole psychological letdown from learning you've had a rebound. ... If you can get by with less treatment, great. But when you start to have a trend toward rebound, I don't think it's worth the risk."

Mangia says her hospital already is using the variable-treatment strategy for all patients with type 2 or type 3 hepatitis C infection.

Based on the study findings, Fontana doesn't think this is a good idea. He praises the Mangia study. Though he notes that it was carefully done and that it addresses crucial issues in hepatitis C treatment, he says doctors and patients would do better to focus on managing side effects than by trying to shorten treatment.

"During the first 12 weeks, the most severe side effects are flu-like symptoms," Fontana says. "Beyond 12 weeks, the depression, the weakness, and the sort of mental aspect becomes more prominent. That is where a lot of patients going out to 48 weeks just can't hack it. By reducing the dose, by seeing patients more often, by introducing antidepressants, and by helping with sleep, you can get a lot of those patients through."

SOURCES: Mangia, A. The New England Journal of Medicine, June 23, 2005; vol 352: pp 2609-2617. Alessandra Mangia, MD, Casa Sollielo della Sofferenza Hospital, San Giovanni Rotondo, Italy. Robert Fontana, MD, associate professor of medicine and medical director for liver transplant, University of Michigan, Ann Arbor. Zeuzem, S. Annals of Internal Medicine, March 2, 2004; vol 140: pp 370-381. AASLD Practice Guideline: "Diagnosis, Management, and Treatment of Hepatitis C," Strader, D. B. Hepatology, April 2004; vol 39: pp 1147-1171.

Posted by Ralph at 07:25 PM | Comments (0)

May 06, 2005

Specific Genes Predict HCV Treatment Success

Wow! Now this is a great discovery. Imagine being able to know in advance if you can be helped by interferon combination therapy. You would not need to go through any discomfort to discover whether or not it would be effective for you.

Toronto, Ontario, May 2 /PR Direct/ -

Identification of specific genes predicts which patients will respond to Hepatitis C treatment

Simple blood test in the near future possible

(Toronto, May 2, 2005) - For the first time, physicians at University Health Network and University of Toronto have identified a small subset of genes that can predict whether a patient with chronic Hepatitis C will be able to respond to current treatments.

These genes could also become the basis of a simple new test in the future to predict which patients will respond to therapy.

The study, published in the May issue of the American Gastroenterological Association's Gastroenterology, found that the difference between those patients who responded to treatment and those who did not was the level of expression - whether the genes were turned on or turned off - of 18 genes.

"Our results demonstrate that a relatively small number of genes can predict response to therapy. These genes may be important to the ability of the patient to eliminate the virus, so studying these genes in more detail will hopefully lead to novel antiviral treatments," said Dr. Ian McGilvray, the senior author of the study. Dr. McGilvray is a transplant surgeon at Toronto General Hospital, University Health Network and an Assistant Professor of Surgery at the University of Toronto. "By manipulating the products of these genes we might be able to improve treatment responses to this chronic disease."

"This information is helpful for patients because it's one more piece of evidence that we hope will encourage 'responder' patients to start and continue treatment for Hepatitis C, despite it's many side effects," said Dr. Jenny Heathcote, a hepatologist at Toronto Western Hospital, University Health Network and Professor of Medicine at University of Toronto, who contributed to the study and treats many of the patients in the study. "We want to be able to give patients as much information as we can, so that they can make the best decisions about their treatment options."

Tony Angelini, 42, was one of the patients in the study who responded to treatment. He is now clear of the virus. "Knowing that you are a responder gives you the courage and the fight to go on. It was devastating, but having the support of my friends and hospital staff really helped me through the treatment. And I wanted to participate in this study so that the research could help others in the future."

The study followed 31 patients with chronic Hepatitis C who were treated at Toronto Western Hospital from October 2001 until May 2004. Hepatitis C is a disease of the liver caused by the hepatitis C virus (HCV). About 230,000 Canadians are infected with it, and about 170 million people worldwide. Over time the viral infection leads to liver damage, cirrhosis and/or liver cancer. It is currently the leading indication for liver transplants.

Liver biopsies were performed on the 31 chronic HCV patients before treatment, and were compared to 20 biopsies from healthy, uninfected livers. 16 patients did not respond to subsequent treatment, while 15 did; both groups were well matched with respect to age, HCV viral load (number of viral particles circulating in the blood), and liver disease activity.

In order to define which genes discriminate between those patients who respond to therapy to those who do not, microarray technology, based in a Banting and Best Department of Medical Research laboratory at University of Toronto, was used to analyze the pattern of genes in all participants. This technology allows scientists to compare levels of expression for tens of thousands of genes on a glass slide - these "gene chips" are the size of a postage stamp. The technology is able to quickly scan the expression of those genes and differentiate between genes which are "turned on" or "turned off". Comparing "genetic fingerprints" allows researchers to rapidly and effectively identify sensitive genetic changes associated with various stages of disease, and hopefully identify the most suitable candidates for specific therapies.

"We went into this experiment without any hypothesis about what to look for," said Aled Edwards, a Professor in the Banting and Best Department of Medical Research at University of Toronto with cross appointments in the Departments of Medical Biophysics and Medical Genetics and Microbiology. He is also a senior scientist at the Clinical Genomics Centre at the University Health Network and Director and CEO of the Structural Genomics Consortium. "We cast a very wide net, looking at 19,000 genes of each of the patients."

The researchers found that the difference between those patients who did not respond to therapy to those who did was a subset of 18 genes. In the non-responders to treatment, 16 genes were turned on and two were turned off. Many of the 16 genes which were turned on are stimulated by interferon, one of the key antiviral agents that the body produces in response to viral infection and a medication that patients currently receive as part of their therapy. "Paradoxically, in the non-responders, the liver is revved up and the genes are responding like mad, but there is something about the response that just does not work," said Dr. McGilvray.

In the near future, determining the levels of a small subset of genes in patients' liver biopsies, with perhaps a simple blood test, may be helpful in deciding who will respond to treatment of chronic Hepatitis C with the current combination therapy using the synthetic antiviral agent ribavirin and interferon. This treatment can currently get rid of the virus in only roughly 50% of persons infected with genotype 1, the most common genotype in North America and world-wide.

The study was supported by grants from the PSI Foundation and the Canadian Institute of Health Research.

University Health Network consists of Toronto General, Toronto Western and Princess Margaret Hospitals. The scope of research and complexity of cases at University Health Network has made it a national and international source for discovery, education and patient care. It has one of the largest hospital-based research programs in Canada, with major research projects in transplantation, cardiology, neurosciences, oncology, surgical innovation, infectious diseases, and genomic medicine. University Health Network is a teaching hospital affiliated with the University of Toronto.

Posted by Ralph at 11:39 AM | Comments (0)

April 20, 2005

Hepatitis C and Diabetes (Type 2)

This article was a real surprise with regard to diabetes and Hepatitis C.

In the conclusions I found this mention quite fascinating: "Approximately 40% of patients with HCV infection will display symptoms of some extrahepatic manifestation during the illness (1). Most extraliver manifestations of chronic HCV infection are immunological..."

This mention that most patients who have symptoms experience immunolgical manifestations was an eye opener. I have long heard that the aches, pains, brain fog, fatigue, etc. that many patients experience are due to the immune system going a bit haywire with the virus circulating in the system. This surely seems to acknowledge that theory.

However, the article does go on to say that the virus also directly affects other organs and tissues in the body besides the liver. This accounts for many of the more serious symptoms people experience that have nothing to do with the liver being infected.

The more I learn about this disease, the more I realized there is to learn.

Hepatitis C Virus Infection and Human Pancreatic [Beta]-Cell Dysfunction

Abbreviations: HCV, hepatitis C virus.

Many patients with chronic hepatitis C virus (HCV) develop type 2 diabetes (1). This prevalence is much higher than that observed in the general population and in patients with other chronic liver diseases such as hepatitis B virus, alcoholic liver disease, and primary biliary cirrhosis. Furthermore, it has been shown that post- transplantation type 2 diabetes appears to be higher among patients with HCV (2). However, the pathogenetic basis for the association between HCV infection and diabetes has not been understood. A direct involvement of the virus in the development of insulin resistance has been proposed, and β-cell dysfunction in HCV-positive patients has been observed in some cases (1). Because HCV can infect many tissues other than the liver (3), we hypothesized that the virus might directly damage insulin-secreting cells. This article suggests that HCV may be present in human pancreatic β-cells and demonstrates that islet cells from HCV-positive patients have morphological and functional defects.

RESEARCH DESIGN AND METHODS- The pancreases of 5 HCV-positive (age 68 9 years, 3 men and 2 women, BMI 25.8 1.6 kg/m^sup 2^) and 10 HCV-negative (age 67 9 years, 6 men and 4 women, BMI 26.8 2.0 kg/m^sup 2^) donors were harvested and studied with the approval of our local ethics committee. Histological studies were performed by immunohistochemistry (using the monoclonal mouse anti-HCV E2 protein, clone IGH222 [Innogenetics, Gent, Belgium]) and electron microscopy, as described elsewhere (4,5). Isolated islets were prepared by enzymatic digestion and density gradient purification, and islet functional and survival studies were accomplished as previously described (5,6).

RESULTS- Histology results are summarized in Fig. 1. No sign of islet cell staining was found in HCV-negative pancreases by immunohistochemistry (Fig. 1A); however, focal or diffuse HCV- positive islet cells were observed in HCV-positive pancreatic glands (Fig. 1B). Positive staining was found in 39 12% of 140 examined islets, and the percentage of stained cells was 54 13% per islet. The appearance of a control β-cell at electron microscopy is given in Fig. 1C, showing the characteristic insulin granules and normally preserved mitochondria. In β-cells from HCV-positive pancreases, the presence of virus-like particles was observed, mainly close to the membranes of Golgi apparatus, which, in turn, appeared hyperplastic and dilated (Fig. 1D). The mitochondria appeared round-shaped with dispersed matrix and fragmented cristae (Fig. 1D). Additional β-cell changes were observed at the level of rough endoplasmic reticulum, which showed long and dilated tubular membranes, with numerous electrondense ribosomes bound to the latter (not shown). These morphological changes were accompanied by reduced in vitro glucose-stimulated insulin release (Table 1); however, apoptosis was similar in control as in infected islet cells (Table 1).

CONCLUSIONS- Approximately 40% of patients with HCV infection will display symptoms of some extrahepatic manifestation during the illness (1). Most extraliver manifestations of chronic HCV infection are immunological; however, the virus may have a direct cytopathic action, because it can infect many tissues other than the liver (3). In the present article we have suggested the presence of HCV infection in pancreatic β-cells of human subjects, and we have provided evidence that this was associated with morphological cell changes and altered islet cell function. The immunohistochemical method we have used to show the presence of infection in islet cells has been previously validated (4), and the electron microscopy morphological alterations of the β-cell are similar to those reported in other cell types during HCV infection (7). The insulin secretion functional defects of islets from HCV-positive donors might contribute to the development of diabetes in predisposed subjects. On the other hand, the absence of increased apoptosis is in line with the observation that reducing viral load is associated with improvement of diabetes in HCV-positive patients (8). In conclusion, the present article proposes that HCV can infect human pancreatic β-cells and that this is accompanied by β-cell dysfunction. A direct cytopathic effect of HCV at the islet cell level is therefore suggested to explain, at least in part, the association between HCV infection and diabetes, especially in predisposed subjects (1).

Table 1-Insulin secretion and apoptosis data of HCV-negative and HCV-positive pancreatic islets

Figure 1-A and B show the results obtained by an immunoperoxidase technique for anti-HCV-E2 in pancreatic islets (original magnification 400). in A, the endocrine cells from a control pancreas are completely devoid of the viral antigen. In B, the endocrine cells from an HCV-positive pancreas show a brown, finely granular staining, indicating the presence of the HCV proteins. C and D show the results obtained by electron microscopy (original magnification 46,000). In C, a control β-cell is shown, with the characteristic insulin granules (G) and normal mitochondria (M). In D, a β-cell from an HCV-positive pancreas is represented, showing virus-like particles (VL) close to dilated, hyperplastic Golgi apparatus (GA) and round-shaped mitochondria with dispersed matrix and fragmented cristae.

A table elsewhere in this issue shows conventional and Systme International (SI) units and conversion factors for many substances.

2005 by the American Diabetes Association.

References

1. Lecube A, Hernandez C, Genesca J, Esteban JI, Jardi R, Simo R: High prevalence of glucose abnormalities in patients with hepatitis C virus infection: a multivariate analysis considering the liver injury. Diabetes Care 27:1171-1175, 2004

2. Bruchfeld A, Wilczek H, Elinder CG: Hepatitis C infection, time in renal-replacement therapy, and outcome after kidney transplantation. Transplantation 78:745-750, 2004

3. Mayo MJ: Extrahepatic manifestations of hepatitis C infection. Am J Med Sci 325: 135-148, 2003

4. Verslype C, Nevens F, Sinelli N, Clarysse C, Pirenne J, Depla E, Maertens G, van Pelt J, Desmet V, Fevery J, Roskams T: Hepatic immunohistochemical staining with a monoclonal antibody against HCV- E2 to evaluate antiviral therapy and reinfection of liver grafts in hepatitis C viral infection. J Hepatol 38:208-214, 2003

5. Marchetti P, Del Guerra S, Marselli L, Lupi R, Masini M, Pollera M, Bugliani M, Boggi U, Vistoli F, Mosca F, Del Prato S: Pancreatic islets from type 2 diabetic patients have functional defects and increased apoptosis that are ameliorated by metformin. J Clin Endocrinol Metab 89:5535-5541, 2004

6. Marchetti P, Lupi R, Federici M, Marselli L, Masini M, Boggi U, Del Guerra S, Patan G, Piro S, Anello M, Bergamini E, Purrello F, Lauro R, Mosca F, Sesti G, Del Prato S: Insulin secretory function is impaired in isolated human islets carrying the Gly(972)[arrow right]Arg IRS-1 polymorphism. Diabetes 51:1419-1424, 2002

7. Falcon V, Acost-Rivero N, Chinea G, Gavilondo J, de la Rosa MC, Menendez I, Duenas Carrera S, Vina A, Garcia W, Gra B, Noa M, Reytor E, Barcelo MT, Alvarez F, Morale-Grillo J: Ultrastructural evidences of HCV infection in hepatocytes of chronically HCV- infected patients. Biochem Biophys Res Commun 305:1085-1090, 2003

8. Bahtiyar G, Shin JJ, Aytaman A, Sowers JR, McFarlane SI: Association of diabetes and hepatitis C infection: epidemiologic evidence and pathophysiologic insights. Curr Diab Rep 4:194-198, 2004

MATILDE MASINI, MD1

DANIELA CAMPANI, MD2

UGO BOGGI, MD3

MICHELE MENICAGLI, MD2

NICOLA FUNEL, MD1

MARIA POLLERA, MD1

ROBERTO LUPI, PHD1

SILVIA DEL GUERRA, PHD1

MARCO BUGLIANI, PHD1

SCILLA TORRI, PHD1

STEFANO DEL PRATO, MD1

FRANCO MOSCA, MD3

FRANCO FILIPPONI, MD4

PIERO MARCHETTI, MD, PHD1

From the 1 Metabolic Unit, Department of Endocrinology and Metabolism, University of Pisa and Pisa University Hospital, Pisa, Italy; the 2 Section of Transplantation Pathology, Division of Surgical, Molecular and Ultrastructural Pathology, Department of Oncology, University of Pisa and Pisa University Hospital, Pisa, Italy; the 3 Referral Center for the Treatment of Pancreas Diseases, Department of Oncology, University of Pisa and Pisa University Hospital, Pisa, Italy; and the 4 Liver Transplant Unit, University of Pisa and Pisa University Hospital, Pisa, Italy.

Address correspondence and reprint requests to Piero Marchetti, MD, Department of Endocrinology and Metabolism, Metabolic Unit, Ospedale Cisanello, Via Paradisa 2, 56124 Pisa, Italy. E-mail: marchant@immr.med.unipi.it.

Received for publication 30 November 2004 and accepted in revised form 29 December 2004.

Copyright American Diabetes Association Apr 2005

Posted by Ralph at 04:47 PM | Comments (0)

April 18, 2005

Early Treatment of HCV Questioned

You are not necessarily going to see information like this printed in the US press. It seems the party line is to not alienate the pharmaceutical industry.

Even when there are suspicions regarding certain drugs or studies there is generally nothing publicly noted until there is undeniable proof (see Bextra, Celebrex and Vioxx).

This article is also the first place I've seen the prognosis differential between infected women and men mentioned.

For doctors to recommend current therapy for anyone who shows up in their office with Hepatitis C seems short sighted, at best, and irresponsible, at least.

Bear this in mind when considering therapy for yourself or a loved one.

Report Questions Early Treatment of Hepatitis C
Monday April 18, 2005 (1525 PST)

ISLAMABAD: People with hepatitis C whose livers remain healthy may be better off not undergoing drug treatment, which can produce severe side effects such as nausea and depression and does not always work, researchers said.

The recommended 48-week course of treatment for the blood-borne virus -- injections of interferon and oral ingestion of ribavarin -- is effective in, at most, 60 percent of patients. It also has potentially severe side effects such as nausea, fatigue, depression and, in some cases, suicidal impulses.

The treatment, which costs in excess of $20,000, has been shown to lengthen the lives of hepatitis C sufferers with existing liver damage, a condition which can lead to deadly cirrhosis or cancer.

But a majority of hepatitis C patients do not develop liver damage before dying of other causes, so the drug treatment may not be cost-effective or helpful for them, the report from the Harvard School of Public Health's Center for Risk Analysis said.

In the United States, 2.7 million people have chronic cases of hepatitis C and there are about 25,000 new cases each year, most infected through needle sharing or from receiving blood from an infected donor. But four out of five have no signs or symptoms and many of them are unaware they have it.

The disease's progression varies considerably and milder cases, especially among women, may never progress to cirrhosis. The report's analysis of U.S. health data showed that the probability of infected men developing cirrhosis over a 30-year period was between 13 percent and 46 percent, and among women the probability was between 1 percent and 29 percent.

"There has been a huge effort over the last few years to identify people infected with (hepatitis C), but this wider group of patients will likely include those who are least likely to develop advanced liver disease," Sue Goldie, author of the report published in this week's issue of the Journal of the American Medical Association said in a statement.

"For patients at low risk of progressing, the overall health gain from treatment may be minimal given the potential for toxic side effects," she said.

Posted by Ralph at 10:30 AM | Comments (2)

April 06, 2005

Retinal Toxicity and Combination Therapy

This article from HIVandHepatitis.com makes a strong statement regarding the possible negative effects of interferon combination therapy on the eyes of patients.

Although warned of in package and label warnings this report brings the very real possiblity of serious damage home in a powerful way.

Retinal Toxicity During Pegylated Alfa Interferon Therapy for Chronic Hepatitis C

By Ronald Baker, PhD

There have been documented and anecdotal reports of ocular side effects during therapy with pegylated interferon and ribavirin. The aim of the current study was to evaluate the effect of therapy with pegylated interferon and ribavirin on the eyes of patients with chronic hepatitis C.

In this small study, 10 patients receiving peginterferon alfa-2a (Pegasys) and ribavirin and 10 healthy volunteers underwent full ophthalmic investigations and multifocal electroretinogram testing at baseline, and at regular intervals during treatment and post-treatment. The multifocal electroretinogram maps retinal function. Responses were compared with sequential recordings from healthy volunteers.

Results

All patients had normal clinical ophthalmic investigations at baseline. During therapy a single patient experienced central visual disturbance lasting 24 h with no prolonged ill effect.

No other patient was aware of any change in vision.

Fundal abnormalities [relating to the retinal area] appeared in five patients during treatment.

The multifocal electroretinogram showed reductions in retinal function in five patients.

Nine of 10 patients exhibited abnormalities on at least one multifocal electroretinogram or fundoscopic investigation.

The authors conclude, "Subclinical retinal toxicity during anti-viral therapy with pegylated alpha-interferon and ribavirin was frequent in this study and it suggests that patients should be warned of this risk and monitored during therapy."

Department of Clinical Physics and Bioengineering, Gartnavel General Hospital, Glasgow, UK.

See also Is Screening for Peginterferon-related Retinopathy in Hepatitis C Justified? and

Treatment with Pegylated Interferon May Cause Eye Complications in Patients with Chronic Hepatitis C

Commentary

Serious ocular disorders do not appear to occur frequently among patients using standard interferon or the peginterferons plus ribavirin. However, such problems can occur. If vision problems develop, patients should immediately call their physician and set up an appointment to see an ophthalmologist for a complete eye examination.

The product information on the pegylated interferons contains a warning about potential ophthalmologic disorders. The following text is excerpted from the WARNINGS section of the Pegasys Product Information (9). There is a similar WARNING on potential ocular disorders associated with peginterferon alfa-2b in the Peg-Intron/Rebetol product information:

“Decrease or loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots, optic neuritis, and papilledema are induced or aggregated by treatment with PEGASYS or other alpha interferons.

“All patients should receive an eye examination at baseline. Patients with preexisting opthalmologic disorders (e.g., diabetic or hypertensive retinopathy) should receive periodic opthalmologic exams during interferon alpha treatment. Any patient who develops ocular symptoms should receive a prompt and complete eye examination.

“Pegasys treatment should be discontinued in patients who develop new or worsening ophthalmologic disorders.” [emphasis added]

Selected Excerpts from the Literature on Retinal Toxicity Related to Therapy with Standard Interferon and/or Pegylated Interferon:

“The incidence of serious ocular pathology associated with anti-HCV therapy may be very high and is probably associated with peg-IFN alpha-2b. Increased monitoring of patients treated with peg-IFN alpha-2b for retinal and visual changes is warranted.” C Farel et al (3).

“Although ocular toxicity is uncommon, it should be emphasized that it can occur any time after the start of interferon therapy, and physicians now treating chronic hepatitis C patients with pegylated interferon must be aware of this potentially serious adverse event.” RA Willson (8).

The multifocal electroretinogram can detect retinal dysfunction in chloroquine retinopathy even when the full-field electroretinogram is normal and retinal alterations are subtle. Kellner et al (5).

“This case report underlines the necessity of an EOG on patients with INF-alpha therapy. Until now, the pathogenesis of this retinal toxicity has been poorly understood. These results show that the retinal pigmented epithelium is probably implicated at an early stage in this retinal toxicity.” M Crochet et al (2)

“Subclinical retinal toxicity during anti-viral therapy with pegylated alpha-interferon and ribavirin was frequent in this study and it suggests that patients should be warned of this risk and monitored during therapy.” Chisolm et al (1)

‘Subclinical neurovisual impairment is a frequent, largely unrecognized complication of low-dose IFN therapy, and patients with chronic hepatitis B and older age appear to be most susceptible. This apparently innocuous complication is long lasting, possibly irreversible in some patients, with yet undetermined consequences on visual function.” Manesis et al (6)

“8/19 patients, while on treatment, developed an asymptomatic retinopathy. Among these 3/8 were relapsers and 5/9 were non-responders to interferon monotherapy. All retinal changes faded, often while the patients continued the therapy. There was no significant association in occurrence of retinopathy with haematological and/or biochemical changes.” Jain et al (4)

“Although ocular toxicity is uncommon, it should be emphasized that it can occur any time after the start of interferon therapy, and physicians now treating chronic hepatitis C patients with pegylated interferon must be aware of this potentially serious adverse event.” Willson (8)

04/06/05

Citations

(1) J A Chisholm and others. Retinal toxicity during pegylated alpha-interferon therapy for chronic hepatitis C: a multifocal electroretinogram investigation. Alimentary Pharmacology & Therapeutics. 21(6): 23-32. March 15, 2005.

(2) M Crochet and others. Retinopathy caused by interferon alpha associated with ribavirin therapy and the importance of the electro-oculogram: a case report. Journal of French Ophthalmolology 27(3):257-262. March 2004.

(3) C Farel and others. Serious ophthalmic pathology compromising vision in HCV/HIV co-infected patients treated with peginterferon alpha-2b and ribavirin. AIDS 18(13):1805-9. September 3, 2004.

(4). K Jain and others. Retinopathy in chronic hepatitis C patients during interferon treatment with ribavirin. British Journal of Ophthalmology 85(10):1171-3. October 2001.

(5). U Kellner, Kraus H, Foerster MH.. Multifocal ERG in chloroquine retinopathy: regional variance of retinal dysfunction. Graefe's Archive for Clinical and Experimental Ophthalmology 238(1): 94-97. January 2000.

(6). E K Manesis and others. Neurovisual impairment: a frequent complication of alpha-interferon treatment in chronic viral hepatitis. Hepatology 27(5):1421-7. May 1998.

(7). A Tsolakos and N Zalatimo. Hepatitis C: a review of diagnosis, management, and ocular complications from treatment. Optometry 74(8): 517-23. August 2003.

(8). R A Willson. Visual side effects of pegylated interferon during therapy for chronic hepatitis C infection. Journal of Clinical Gastroenterology 38(8): 717-722. September 2004.

(9). Hoffman-La Roche. WARNINGS: Ophthalmologic Disorders. Pegasys Product Information. Page 10. January 2004.

Posted by Ralph at 03:32 PM | Comments (1)

April 05, 2005

Coffee Reduces Chances of Liver Cancer

I drink a lot more green tea than coffee. This report makes me want to drink at least one cup of coffe per day even if just for therapeutic reasons.

Very convincing results to this study make this report very credible.

Coffee Consumption Reduces the Risk of Liver Cancer

Coffee Beans

Over the past 20 years, a body of data has accumulated that suggests a clear benefit for liver function and liver disease from drinking coffee. Several studies have demonstrated that drinking coffee lowers gamma-glutamyltransferase (GGT) activity, especially among heavy alcohol drinkers. In a Japanese study of 2494 men, the mean GGT was about 30% lower among those who drank 4 or more cups of coffee daily compared to non drinkers.

Although GGT is a relevant indicator of the risk for cirrhosis, serum alanine aminotransferase (ALT) activity is a more specific marker of liver injury, and a few population-based surveys from Italy and Japan have found a similar inverse relation between coffee drinking and ALT levels.

Results of a study by Gelatti et al published in the current issue of the Journal of Hepatology (April 2005) provide more evidence of an inverse relation between drinking coffee and hepatocellular carcinoma (HCC) [liver cancer].

The aim of this study was to investigate the role of coffee in HCC, taking the main risk factors into account. Researchers conducted the study in northern Italy, where they enrolled 250 hepatocellular (HCC) patients and 500 controls who had been hospitalized for any reason other than neoplasms and liver and alcohol-related diseases.

A standardized questionnaire provided information to the investigators concerning the patients' lifetime history of coffee.

Results

Coffee consumption by the study group in the decade prior to the questionnaire/interview was associated with a decreasing risk of HCC with a clear dose-effect relation.

With respect to non coffee drinking participants, the odds ratios (ORs) were: 0.8, for 1-2 cups/day, 0.4 for 3-4 cups/day and 0.3 for 5 or more cups/day.

The ORs for HCC decreased for drinking >2, compared to 0-2 cups/day of coffee, for an alcohol intake >80g/day, for presence of hepatitis B virus infection or hepatitis C virus infection.

The authors conclude, "Coffee drinking was inversely associated with hepatocellular carcinoma regardless of its etiology."

Discussion

Compared with non coffee drinkers, the relative risks (RRs) were 0.8 for drinkers of 1-2 cups per day, 0.4 for those of 3-4 cups, and 0.3 for drinkers of five or more cups per day. The inverse relation between coffee and primary liver cancer is stronger than in previous studies, indicating that the relation is probably real, and not due to chance.

The combined, pooled RR from three published studies of coffee and hepatocellular carcinoma for drinkers of three or more cups of coffee per day as compared to non coffee drinkers is approximately 0.6.

More important, the study by Gelatti et al. provides original information on the independent effect of coffee from the major recognized risk factors for primary liver cancer. The inverse relation with coffee, in fact, was of similar magnitude in subjects negative or positive for HBV or HCV serum markers, as well as in non- or moderate drinkers and in heavy drinkers.

Coffee appears to have a real, but moderate effect in reducing the risk of hepatocellular carcinoma. Various components of coffee have been related to such a favorable effect, including caffeine, coffee oils kahweol or cafestol, and antioxidant substances from coffee beans, but no definite evidence is available for any of these components.

Despite these uncertainties, HCC should be added to other digestive tract cancers on which a favorable role of coffee drinking has been suggested, including oral and pharyngeal, oesophageal and colorectal cancers.

04/04/05

References
U Gelatti and others (for the Brescia HCC Study Group). Coffee consumption reduces the risk of hepatocellular carcinoma independently of its aetiology: a case-control study. Journal of Hepatology 42(4): 528-534. April 2005.

C La Vecchia. Coffee, liver enzymes, cirrhosis and liver cancer (Editorial). Journal of Hepatology 42(4): 444-446. April 2005.

Posted by Ralph at 03:24 PM | Comments (0)

March 16, 2005

Mother to Child HCV Transmission Studied

The article mentions the incidence of mother to child transmission is very low. Of those infected, fully one third contracted the disease in utero. It seems these were mostly genotype 1. Clearly more study is recommended.

When Does Mother-to-Child Transmission of Hepatitis C Virus Occur?

The rate of HCV transmission from mother to child is generally though to be very rare. However, it does occur, however rarely. The aim of the present prospective cohort study was to investigate when hepatitis C virus (HCV) infection from mother to child occurs, and to evaluate possible associated factors.

Fifty-four HCV positive children and their mothers were tested within three days of birth. The main outcome measure of the study was HCV RNA polymerase chain reaction (PCR) results.

Results

Seventeen of the children (31%) were positive in the first 3 days of life and could be assumed to have acquired infection in utero.

Testing PCR positive was not associated with sex (53% v 49% boys; p=0.77) or mode of delivery (29% elective caesarean section in both groups; p=0.98).

Children with evidence of intrauterine infection were significantly more likely to be of lower birth weight and infected with genotype 1 (58% v 12%, p=0.01).

Although a higher proportion of infants born to HCV/HIV co-infected women were HCV PCR positive in the first 3 days of life, this difference did not reach statistical significance.

Excluding infants born to co-infected women did not affect the results.

Thirty seven of the children (68%) were negative in the first 3 days of life, 27 of whom were positive when tested again at 3 months, and nine were first PCR positive after 3 months (one child had no further tests).

Conclusions

The authors conclude, “These results suggest that at least one third and up to a half of infected children acquired infection in utero. Although postpartum transmission cannot be excluded, these data suggest that it is rare. The role of HCV genotypes in the timing and mechanism of infection should be explored further.”

Paediatric HIV Service, Royal Hospital for Sick Children, Edinburgh, Scotland, UK.

03/16/05

References
J Mok and others (for the European Paediatric Hepatitis C Virus Network). When does mother to child transmission of hepatitis C virus occur? Arch Dis Child Fetal Neonatal Ed 90(2): F156-160. March 2005.

Posted by Ralph at 11:56 AM | Comments (0)

March 10, 2005

Treating Non-responders

I'm not a mathematician, but it seems to me that one with those skills could discern from this article what the SVR rate among genotype 1 patients is after initial treatment and what it is after retreatment.

The article states that about 45% of patients are unresponsive to treatment. We know that genotypes 2, 3, are more responsive (each one is different, but I've heard that two is up over 85%).

They mention the results for non 1 genotypes but not for 1.

If anyone reading this can do the math, please post it.

Thanks.

Gastroenterologie
Clinique et Biologique

Volume 29 No 2 de March 2005

Treatment of chronic hepatitis C in patients unresponsive to interferon

Aim

About 45% of patients with chronic hepatitis C are unresponsive to the present reference treatment combining pegelated interferon plus ribavirin; before pegylated interferon was available the non-response rate was around 60%. This open multicenter pilot study, initiated before pegylated interferon became available, was designed to evaluate, in patients unresponsive to interferon monotherapy, the rate of biological and virological response and side-effects of the ribivirin- alpha 2b interferon combination.

Methods

The combination protocol was ribavirin (1 to 1.2 g/d) plus alpha 2b interferon at induction doses (9 MU/d the first week; 4.5 MU/d the eleven following weeks; 3 MU/2 days the 36 following weeks).

Results

Among the 27 included patients, 17 (63%) were viremia-negative (PCR) after 12 weeks of treatment, 9 (33%) were complete responders (undetectable viremia and normal transaminases) at the end of treatment (48 weeks) and of follow-up (72 weeks). Patients with non-1, non-4 genotypes who derived full benefit from this therapeutic strategy (6/7 (86%) were complete responders: 4/5 with genotype 3 and 2/2 with genotype 5). Quality-of-life was impaired during treatment, especially during the first 12 weeks of high-dose interferon therapy.

Conclusion

While waiting for new therapeutic possibilities, these good results suggest interferon induction at the beginning of treatment remains a valid option.

Posted by Ralph at 11:31 AM | Comments (1)

February 24, 2005

Increased Cancer Risk With HCV

The following report seems scary at first. A significantly higher incidence of two serious types of cancer in Hepatitis C patients is certainly important. But, the normal incidence of non-hodgkin's lymphoma is just 12 cases per 100,000 worldwide in 2001. So, with double the incidence that would be just 24 cases per 100,000 Hepatitis C patients. Not exactly a widespread or common situation.

It is very important to keep reports like these in perspective.

Normal multiple myeloma incidence is approximately 6 cases per 100,000 population in the US. So, 2.5 times that, is just 15 cases per 100,000 Hepatitis C patients.

Cancer in patients with hepatitis C
24 Feb 2005

People infected with the hepatitis C virus (HCV) have a higher risk of developing non-Hodgkin's lymphoma and multiple myeloma, according to a recent study of the Swedish population. These findings are published in the March 2005 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). Published by John Wiley & Sons, Inc, the journal is available online via Wiley InterScience: http://www.interscience.wiley.com/journal/hepatology.

Previous studies have shown that people with HCV have a higher risk of developing cirrhosis and liver cancer, however, studies of the association between HCV and other malignancies have yielded varied and conflicting results. In Sweden, a cluster of four cases of non-Hodgkin's lymphoma in 554 HCV patients raised the question of an association between those two diseases and other related cancers in the country's population.

To evaluate this possibility, researchers, led by Ann-Sofi Duberg of Örebro University Hospital in Sweden, gathered data from the Swedish Institute for Infectious Disease Control and the Swedish Cancer Registry to examine the incidence of non-Hodgkin's lymphoma, multiple myeloma, chronic lymphatic leukemia, acute lymphatic leukemia, Hodgkin's lymphoma and thyroid cancer in the country's entire cohort of HCV patients.

For 27,150 HCV patients, the researchers modelled the date of HCV infection based on age and mode of transmission. They then collected data on the relevant cancer diagnoses among these patients for the time period from 1990 to 2000, excluding those whose HCV diagnosis was within 3 months of their cancer diagnosis. Lastly, they performed statistical analyses to compare these patients' cancer rates to those of the entire Swedish population.

They found that the risk of both non-Hodgkin's lymphoma and multiple myeloma were significantly higher compared to the general population - 1.99 and 2.54 times higher, respectively. Their risk of chronic lymphatic leukemia and thyroid cancer were not significantly higher, and the incidence of both acute lymphatic leukemia and Hodgkin's lymphoma was too low to be included.

"The majority of the non-Hodgkin's lymphoma and multiple myeloma patients were estimated to have been infected more than 15 years, which is consistent with the theory that lymphomagenesis is a slow process and non-Hodgkin's lymphoma develops after a long influence," say the authors. They suggest that the risk for HCV-related malignancy increases with time of HCV infection.

As in many countries, Sweden has had an increase in the incidence of malignant non-Hodgkin's lymphoma in recent years. As most Swedish HCV patients were born after 1950, the cancer increase might be related to long-lasting HCV infection.

In conclusion, "this is the first study of the incidence of non-Hodgkin's lymphoma, multiple myeloma, chronic lymphatic leukemia, acute lymphatic leukemia, Hodgkin's lymphoma and thyroid cancer in a nationwide cohort of HCV-infected persons," the authors report. "Although the delayed diagnosis of hepatitis C most probably has made us underestimate the risk, this study showed that the risk of B-cell non-Hodgkin's lymphoma and multiple myeloma were significantly increased."

--------------------

Article: "Non-Hodgkin's Lymphoma and Other Nonhepatic Malignancies in Swedish Patients With Hepatitis C Virus Infection," Ann-Sofi Duberg, Marie Nordström, Anna Törner, Olle Reichard, Reinhild Strauss, Ragnhild Janzon, Erik Bäck, and Karl Ekdahl, Hepatology; 41:3; March 2005 (DOI: 10.1002/hep.20608).

Posted by Ralph at 08:31 PM | Comments (0)

February 23, 2005

HCV Hides From Immune System

The conclusion of this study, that HCV disguises itself to appear to be part of the patient's own immune system, is very intruiging. Not just because it helps explain why HCV becomes chronic in 85% of people who contract it, but also because many of the extrahepatic symptoms of HCV appear to be similar to certain auto immune disorders.

Autoimmune disorders are when the immune system of the body actually begins to attack the body. Is the fact that the virus disguises itself as part of the immune system partially responsible for this? It seems more research is needed. So stay tuned...

Canadian scientists may have found why hepatitis C triggers chronic infection

Helen Branswell
Canadian Press
Wednesday, February 23, 2005

TORONTO (CP) - A team of Canadian researchers believes it has unravelled the mystery of how hepatitis C evades the human immune system to cause chronic disease in about three-quarters of the people who become infected.

Their discovery provides a bright ending to the personal tragedy of the hepatitis C patient whose blood they studied, a man who became infected through a medical error in a hospital clinic.

The researchers report that the virus escapes detection because its external coat mimics immunoglobulin, one of the immune system's warriors. Further, the virus may evolve to maintain or improve its camouflage as time goes on, they suggest.

Because the immune system is set up to attack only things it considers foreign, it does not attempt to destroy the virus.

"If you want to hide in a forest, it's often good to look like a tree," explained Dr. Earl Brown, a virologist at the University of Ottawa and senior author of the paper.

The team came to its conclusions by studying blood drawn from the first infected blood donor caught by heightened screening methods put in place after Canada's tainted blood scandal. The man was so newly infected with hepatitis C that his immune system hadn't yet responded to it. As a consequence, the scientists were able to chart that response over time.

"We watched it (the virus) walk into the forest," Brown said, continuing with his metaphor.

The blood donor had become infected in an Alberta hospital in the spring of 2000 while receiving intravenous antibiotics. Now living in southeastern British Columbia, he's pleased his misfortune may help science figure out how to foil the virus.

"It was such a bizarre sequence of events that I wanted to see some good come out of it," said Randy, 47, who asked that his surname not be made public.

"This might be something that could potentially lead to a cure or a better treatment for a lot of people. And that kind of drives you along on this," said Randy, who was cleared of infection in 2003 after two courses of treatment with expensive anti-viral drugs.

However, Brown said the findings - reported in this week's issue of the journal Virology - suggest a vaccine for hepatitis C may be an elusive, even dangerous target that could backfire by prompting the immune system to attack itself.

The team, which also involves scientists from Canadian Blood Services and the Alberta provincial laboratory of public health, compared the genetic codes for the virus's envelope with those of some components of the immune system, finding areas where the virus appeared to be mimicking the body's defenders.

The findings will influence future research into not just hepatitis C but other viruses that don't provoke an extended immune response, Brown said.

"It's going to change the way (scientists) think in hepatitis C (research) for sure, and probably a bunch of other diseases. It's impossible for it not to."

Others interpreted the findings more cautiously.

"It's an intriguing hypothesis but I think at this point it's really only a hypothesis," said Dr. Jake Liang, chief of the liver diseases branch of U.S. National Institute of Diabetes and Digestive and Kidney Diseases.

Liang, an expert in viral hepatitis, said the study was well done. But he and others believe the whole notion of viral "mimicry" is overhyped.

"A lot of these hypotheses are based on very weak evidence. It does have some appeal to it. Sounds good. But very few of them have ever been proved to be causal," Liang said.

Dr. Mel Krajden of the British Columbia Centre for Disease Control said he doubted the mechanism identified is the full answer to why some hepatitis C infections become chronic.

"I'm sure it's more complex than just this," said Krajden, who heads the centre's hepatitis service.

It is estimated that about 240,000 Canadians are infected with hepatitis C, which causes inflammation of the liver that can lead to cirrhosis or liver cancer.

It spreads from person to person via contact with infected blood. Shared drug paraphernalia - needles, pipes and straws - are currently the main vehicle of transmission, though prior to changes in blood screening methods, blood transfusions were also a key source of infection. The virus can also be transmitted during sex with an infected person, although the risk is low.

In about 20 or 25 per cent of cases, people will spontaneously clear the virus. The remainder are chronically infected, though treatment with anti-viral drugs appears to cure some - though not all - cases.

Posted by Ralph at 05:52 PM | Comments (0)

February 07, 2005

HCV article from Amednews.com

The following article is from Amednews.com (American Medical News, The Newspaper For America's Physicians). This is a publication of the American Medical Association. I find it interesting to see what doctors are hearing about Hepatitis C from their own association.

Again, because genotype 1 infects approximately 70% of Americans it is important to note the success rates reported. According to this article somewhere between 30 and 40% success is being experienced with genotype 1, depending upon race (interferon combination therapy is significantly less effective for African Americans).

The article ends on an up note regarding emerging therapies---particularly protease inhibitor types (as we have previously pointed out here).

Larger gains sought in hepatitis C treatment

Despite some success, the viral disease is still the most common chronic bloodborne infection in the United States.

By Susan J. Landers, AMNews staff. Feb. 14, 2005.

Washington -- There are still gains to be made in the treatment of hepatitis C, and a recent congressional hearing on the disease as well as a National Institutes of Health workshop to discuss a vaccine to fight this liver-ravaging condition hold out hope for more progress.

"In the last 10 years, we've quadrupled the treatment response rate," said Michael Bernstein, MD, director of the Hepatitis Clinic at Coney Island Hospital in Brooklyn, N.Y.

There is now an overall success rate of about 55%, researchers say. Treatment with long-acting interferon or a combination of interferon and other antiviral drugs has made the difference.

"We are still, however, left with those unfortunate 45% who don't respond," said Adrian M. DiBisceglie, MD, chief of hepatology at Saint Louis University School of Medicine.

And that's a lot of people. Hepatitis C is the most common chronic bloodborne infection in the United States. About 4 million Americans are chronically infected, and most are not even aware of this threat to their health.

Primary care physicians have a major role to play in diagnosing the infection, so that those who can benefit from treatment will receive it in time to prevent extensive liver damage, Dr. Bernstein said. The AMA and the Centers for Disease Control and Prevention have collaborated on materials targeted to doctors and patients to help with early diagnosis.

"Hepatitis C was only identified 15 years ago, so we still have much to learn about this disease," said Rep. Tom Davis, (R, Va.), chair of the House Committee on Government Reform. Davis held a hearing on hepatitis C Dec. 14, 2004.

An NIH workshop on vaccine development was scheduled for Feb. 1 and 2.

Early warning system

Hepatitis C infection often presents no warning symptoms, and many people could have unknowingly become infected from intravenous drug use years earlier or from contaminated blood or blood products received before widespread screening for the virus began in the early 1990s.

The virus is sometimes only discovered after a patient exhibits signs of serious liver disease, such as cirrhosis or liver cancer, Davis said.

Still, the forward march of treatment has resulted in substantial gains for many of those infected. "We started out treating patients with hepatitis C in the mid-80s with interferon," Dr. DiBisceglie said. At that stage, no more than 5% to 10% of patients had a sustained virologic response, he added.

Treatment refinements made since then include the use of combination therapy with pegylated interferon and ribavirin that extends the life of interferon, thus allowing it to fight the virus longer.

Today's positive outcomes jump even higher for those infected with one of the less common viral genotypes. For those infected with genotype 2 the success rate is probably 90%, and for genotype 3, it's about 70% to 80%, Dr. Bernstein said.

However, treating genotype 1 infections, the most common of the viral types, has not met with as much success. African-Americans, for whom the cure rate is the lowest, are most frequently infected with this genotype.

But it isn't just infection with genotype 1 that is making the difference in this population, Dr. DiBisceglie said. "Even if you account for genotype, the response rate is less than in whites," he said. While about 40% of whites with the genotype respond to treatment, the level drops to 30% to 40% for African-Americans. Studies are under way to examine the possible reasons for the poorer response rate.

A lesson can be drawn from this conundrum, said Stanley M. Lemon, MD, professor of microbiology and immunology at the University of Texas Medical Branch in Galveston and director of the Hepatitis Research Center there.

 That lesson is to include all populations in clinical studies, he said. "If you have selected populations that don't really need to be treated by the drug, you are going to lose valuable information."

Work also has been ongoing to develop an effective vaccine, and some candidates are currently being tested. But the complex nature of the virus presents many obstacles.

"The problem is, like the AIDS virus, the envelope proteins you would likely target mutate very quickly," Dr. Bernstein said, which makes it much more difficult to design a vaccine. In contrast, proteins in hepatitis B, for which a successful vaccine has been developed, are much less variable.

Dr. Lemon finds promise in the development of small molecule antiviral inhibitors, which have been shown to cause a sharp drop in hepatitis C viral levels in a short time. Although studies of one such drug were halted because of high toxicity, others could meet with more success. "The importance of those studies, even if that drug never makes it to market, is that small molecule therapy, antivirals like we have for HIV and herpes, are nearing reality and have incredible potential," Dr. Lemon said.

Posted by Ralph at 11:24 AM | Comments (0)

February 02, 2005

HCV On List of Cancer Causing Agents

This announcement is not news to most Hepatitis C patients. We have been told about the possible long term risks associated with Hepatitis C and liver cancer has always been included among them. However, and this needs to be stated, compared to the number of patients with chronic Hepatitis C, the number of patients who develop Hepatocellular Carcinoma (liver cancer) is very small.

The huge majority of patients are not at risk. But, it doesn't hurt to behave as if we all are. That is why I always recommend choosing a lifestyle, diet, and nutritional supplementation that will protect and support your liver (along with any therapy you might choose to do---pharmaceutical or otherwise).

New entries on list of cancer-causing agents

Monday, January 31, 2005 Posted: 2:26 PM EST (1926 GMT)

WASHINGTON (AP) -- The government on Monday added 17 substances to the official list of cancer-causing agents, including the first viruses: hepatitis B and C and some human papillomaviruses that cause common sexually transmitted diseases.

Lead and lead compounds, X-rays, compounds found in grilled meats and various substances used in textile dyes, paints and inks are among the other new listings, the Department of Health and Human Services said in releasing the 11th edition of the federal Report on Carcinogens.

The additions bring to 246 the total number of substances that either are "known to be human carcinogens" or "reasonably anticipated to be human carcinogens." The report now lists 58 "known" -- including the viruses -- and 188 "reasonably anticipated" substances.

Hepatitis B and C, which cause liver disease, were added because studies in humans show that chronic infections cause liver cancer. Some of the human papillomaviruses, which are sexually transmitted, were included because studies show they cause cervical cancer in women, the department said.

Federal law requires the HHS secretary to publish the report every two years.

Posted by Ralph at 07:25 AM | Comments (0)

January 27, 2005

HCV Market Analysis Redux

Here is another press release regarding the state of the market for Hepatitis B and C treatment. The press release is about the industry report available from Research and Markets, an industry research organization. It is the same report referenced by DataMonitor in my January 12th update.

Incidentally, the price of this report is $15,200.

Please note, this report states that "the needs of non-responders, genotype 1 and intolerant patients will not be satisfied in the short term." It also suggests that the pharmaceutical companies look to "tap into a substantial amount of unidentified cases or meet the needs of non-responder or difficult to treat patients.

Press Release
Source: Research and Markets

Hepatitis B and C - Winning Battles But Not The War
Thursday January 27, 8:01 am ET

DUBLIN, Ireland--(BUSINESS WIRE)--Jan. 27, 2005--Research and Markets (http://www.researchandmarkets.com/reports/c12272) has announced the addition of Stakeholder Insight: Hepatitis B & C - Winning Battles But Not The War to their offering

According to the WHO, 350-400 million are chronically infected with HBV and 170-200 million with HCV. Although HBV vaccination and routine screening of donated blood has decreased incidence, the death toll resulting from chronic disease, cirrhosis and HCC is as high as one million per year (WHO, 2002). For HCV related conditions, this number will increase further over the next 10-20 years.

Despite substantial prevalence for both HBV and HCV, the incidence of new infections within the seven major markets has reduced over the last decade due to HBV vaccination, increased blood and pre-natal screening along with awareness campaigns regarding routes of transmission. Our recent physician survey indicates that while diagnosis rates of HBV have remained flat since 2002, HCV diagnosis rates have increased 2-4 fold, with highest growth in Japan

Increased uptake and aggressive life-cycle management of peginterferons (plus ribavirin) have driven the current standard of care to 73% of first-line choice for HCV. Our physician research (180 respondents) reveals higher use of branded peginterferon plus ribavirin packages, where consistency was cited as key selection criterium. Again, the treated patient pool will be increased by higher diagnosis, redefinition of 'normal' ALT and maintenance therapy. However, the needs of non-responders, genotype 1 and intolerant patients will not be satisfied in the short term.

Scope of Report

• Comprehensive overview of HBV and HCV epidemiology with comment on latest dynamics

• Analysis of drug treatment choice per line therapy per region for both HBV and HCV

• Discussion with key opinion leaders with regard to clinical and non-clinical attributes of therapy

• Future outlook for new HBV and HCV therapies along with unmet needs assessment

Highlights

• While diagnosis rates of HBV have remained flat since 2002, HCV diagnosis rates have increased 2-4 fold with highest growth in Japan.

• Based on current estimates of prevalence, diagnosis and treatment current patient pools of between 1.8-2.0 million per disease.

• To increase the treatment pool, manufacturers of hepatitis treatments can either tap into a substantial amount of unidentified cases or meet the needs of non-responder or difficult to treat patients.

Posted by Ralph at 12:14 PM | Comments (0)

Caffeine, HCV and Liver Health

The following report is of interest because I've heard for many years that liver patients need to abstain from caffeine consumption. To be honest, I've consistently included about a cup a day in my diet (along with a pot of green tea and lots of water).

This article makes me feel better, still, about my choice. I never thought of it as being therapeutic, I just figured that one cup would not do much damage (if any).

Even though it is only one study, this is a fairly large study.

Incidentally, I do not drink any alcohol at all anymore. It is common knowledge that alcohol is a potent liver toxin. In fact, it is used in a medical procedure to kill small liver cancer tumors. They actually inject alcohol into the specific site of the tumor because alcohol is such and effective and efficient liver cell killer.

Coffee and Caffeine Consumption Reduce the Risk of Elevated Serum Alanine Aminotransferase Levels

Based on experimental and epidemiologic studies, researchers at the National Institute of Diabetes and Digestive and Kidney Diseases investigated whether coffee and caffeine consumption reduced the risk of elevated alanine aminotransferase (ALT) activity in persons at high risk for liver injury in a national, population-based study.

Participants were 5,944 adults in the Third US National Health and Nutrition Examination Survey, 1988–1994, with excessive alcohol consumption, viral hepatitis, iron overload, overweight, or impaired glucose metabolism.

Liver injury was indicated by abnormal serum ALT activity (>43 U/L).

Results

Elevated ALT activity was found in 8.7% of this high-risk population.

In unadjusted analysis, lower ALT activity was associated with increasing consumption of coffee (P = .001) and caffeine (P = .001). Multivariate logistic regression analyses showed that the risk of elevated ALT activity declined with increasing intake of coffee (P for trend = .034) and caffeine (P < .001).

Comparing persons who drank more than 2 cups per day with non coffee drinkers, the odds ratio was .56 (95% confidence interval, .31–1.0). Comparing persons in the highest caffeine quintile with the lowest, the odds ratio was .31 (95% confidence interval, .16–.61).

These relationships were consistent across subgroups at risk for liver injury and were relatively unchanged when analyses included the entire population or when limited to persons without impaired liver function or right upper quadrant pain.

Fasting insulin concentrations did not mediate the effects.

In conclusion, the authors write, “In this large, national, population-based study, among persons at high risk for liver injury, consumption of coffee and especially caffeine was associated with lower risk of elevated ALT activity.”

This study was supported by a contract from the National Institute of Diabetes and Digestive and Kidney Diseases.

01/21/05

Reference

C E Ruhl and J E Everhart. Coffee and caffeine consumption reduce the risk of elevated serum alanine aminotransferase activity in the United States. Gastroenterology 128(1): 24-32. January 2005.

Posted by Ralph at 08:01 AM | Comments (3)

January 24, 2005

Hepatitis C Treatment Study Being Questioned

A lot of time, money and effort is being spent on this study when other (more effective and less toxic) treatments could be being developed, instead. It seems like comparing two brands of aspirin. In the long run, there is so little difference that it just comes down to what the marketing people choose to advertise and how.

Also, I am suspect of any study funded by an entity that has a vested interest in the final result. Call me suspicious, call me skeptical, but conflict of interest is a known problem wherever it exists. If the study shows the Roche product is better can we really expect Schering not to put some kind of spin on it to do major damage control? We are talking about a billion dollar annual business (Hepatitis C treatment). What do you think?

Posted by Ralph at 06:46 AM | Comments (2)

Biopsy Unnecessary for Successful Hepatitis C Treatment

This article reports on a study that shows biopsy need not be required to treat chronic Hepatitis C. The statistically significant results show that other indicators (ultrasound, fibrosis blood tests, etc.) can suffice when measuring liver damage and treatment success. Because biopsy is an invasive medical procedure with known risks, proceeding successfully without biopsy would be a preferred approach.

Also of note in this report are the success rates. Sustained virologic response was seen in 41 to 43.6% of patients. I keep seeing results like this and can't help wondering how the common knowledge (and that preached by most doctors) is better than a 50% success rate.

Treatment of Patients with Chronic Hepatitis C with or without Liver Biopsy

Expert consensus recommends liver biopsy before therapy for chronic hepatitis C. A cost effectiveness analysis suggested that the best strategy in the management of patients was to treat without biopsy.

In this study, researchers compared therapy in patients who did, or did not undergo biopsy.

Hepatitis C virus (HCV)-positive patients (78) who did not agree to (n = 57) or with contraindications to liver biopsy (n = 21) (group A) were matched for age, sex and genotype with those who consented (group B).

Before therapy (interferon/ribavirin for 12 months), all patients must have received a clinical diagnosis of chronic hepatitis, on the basis of standard biochemical and ultrasonographic parameters. The two groups showed similar baseline characteristics.

A noninvasive, diagnosis of chronic hepatitis was made in 75.6% of group A, and in 83.3% of group B (P = 0.26). Concordance between clinical and histological diagnosis in group B amounted to 91%.

End-of-therapy virological response was 52.6% in group A, and 57.7% in group B (P = 0.63). Sustained virological response was 41.0% and 43.6% in the two groups (P = 0.87).

Predictors of sustained response were noninvasive diagnosis of chronic hepatitis (P = 0.006), lack of portal hypertension (P = 0.037), platelets >105/mm3 (P = 0.007), prothrombin >70% (P = 0.02), and genotype 2 or 3 (P < 0.0001). At multivariate analysis, genotype (P < 0.0001) and platelets (P = 0.004) maintained their predictive power.

The authors conclude, “In most patients with HCV infection, virological clearance after therapy can be achieved irrespective of whatever a liver biopsy might show.”

01/19/04

Reference

A Andriulli and others. Treatment of patients with HCV infection with or without liver biopsy. Journal of Viral Hepatitis 11(6): 536-541. November 2004.

Posted by Ralph at 06:19 AM | Comments (0)

January 14, 2005

Hepatitis C Treatment Depression May Affect Outcome

This article surprised me. I'm not sure what to think of emotional depression as an indicator of treatment success. What is it about the virus or the treatment that causes non-responders to become more clinically depressed than responders during treatment?

Incidentally, this study was co-funded by Schering and the CDC. And, yet, it only claims a 40-50 percent rate of clearing the virus among patients. This is with a supposed 80 percent clearance for genotype 2. How low must the clearance rate actually be for genotype 1? Closer to 30 percent is my guess.

Depression caused by common treatment for hepatitis C may affect outcome

ATLANTA–An article appearing in the January 2005 issue of Brain, Behavior and Immunity suggests that developing depression while on interferon-alpha plus ribavirin may impact how well the medications work.

In a study conducted in the Department of Psychiatry and Behavioral Sciences at Emory University School of Medicine, Charles L. Raison, MD, Andrew Miller, MD, and colleagues, observed that patients who develop depressive symptoms during interferon-alpha plus ribavirin therapy were significantly less likely to have cleared the hepatitis C virus from their blood following six months of treatment.

"Hepatitis C infection affects three to five million Americans, and is the leading cause of liver transplantation," said Dr. Raison. "With advances in treatment, 40-50 percent of patients can be cleared of the virus. Unfortunately, however, the current treatment for hepatitis C – interferon-alpha plus ribavirin – produces a high rate of psychiatric side effects that have long been recognized as impediments to successful antiviral therapy. In the past we primarily worried that depression interfered with quality of life, or would cause patients to stop taking the medicine. These new data suggest that even if patients stay on treatment, they are less likely to have a good outcome if they develop depressiom."

The study examined 103 participants who received pegylated interferon-alpha-2b plus ribavirin (PEG IFN/ribavirin). All participants were psychiatrically evaluated prior to initiation of the medication and at 4, 8, 12 and 24 weeks of PEG IFN/ribavirin treatment.

Only 34% of the patients who had a significant increase in depression cleared the hepatitis C virus from their blood at 24 weeks, as compared to 59%-69% of patients with milder increases in depression. The effect of depression on viral clearance persisted even after adjusting for factors known to affect treatment outcome, such as viral genotype, or whether medications had to be reduced.

"The findings of this study provide preliminary evidence that baseline mood state should be assessed in patients prior to commencing treatment," said Dr. Raison. "Significant deviations from this state may increase the likelihood of treatment failure. Moreover, these findings provide further support that the development of depression can have a negative impact on health outcomes in medically ill subjects."

Researchers from the Rollins School of Public Health, Emory University and the Department of Medicine, Gasteroenterology and Hepatology, Weill Medical College of Cornell University were also involved in the study. The study was supported by grants from the National Institute of Mental Health, Schering–Plough, and the Centers for Disease Control and Prevention.

Posted by Ralph at 05:07 PM | Comments (0)

January 12, 2005

Chronic Hepatitis B and C: Chronic Lack of Effective Treatment

The following article is from Pharmalive.com (The Pulse of the Pharmaceutical Industry).

The first interesting statistic I noticed is the statement that with the easier to treat genotypes they claim an 80% success rate and when factoring in the harder to treat (read genotype 1) the overall rate is around 50%.

While admitting I am no math whiz, it appears that the success rate for Genotype 1 must be well below 50% to end up with a 50% success rate when combined with the 80% claimed for other, more treatable, genotypes.

The authors of this article call current pharmaceutical therapies for chronic viral hepatitis b and c "inadequate", "sub-optimal" and "far from perfect". Remember, this is the "Pulse of the Pharmaceutical Industry" speaking.

 Certainly, in my opinion, if I were to choose between the Roche or Schering therapies, I would choose Roche. For a few reasons, it seems to be the superior choice.

 The authors are pointing out opportunity for pharmaceutical companies to come up with better solutions than currently exist. Especially for the harder to treat varieties like HCV genotype 1. This opportunity is what will drive these drug companies to continue to scramble to develop new treatments.

 As I've said all along, their shareholder-driven need for profits will, ultimately, work to the advantage of patients.

 

 

 

 Chronic Hepatitis B and C: Chronic Lack of Effective Treatment

 LONDON, Jan. 12, 2005--The World Health Organization (WHO) estimates that one-third of the entire world’s population has been exposed to hepatitis B (HBV) resulting in an estimated

 350-400million chronically infected patients globally. Most of these patients reside in Southeast Asia and Sub-Saharan Africa and in most cases are infected at birth. However the seven major pharmaceutical markets* (including the USA) are estimated to harbour up to seven million chronic carriers, with transmission occurring primarily through sexual contact during adulthood. Additionally, while Hepatitis C (HCV) infection is less common, the WHO estimates the numbers of chronically infected individuals at a further 200m. Perhaps most frightening of all however, is that less than one third of patients with either chronic hepatitis B or C (CHB or CHC) are actually receiving treatment.

 Viral hepatitis – a significant public health problem

 Globally, HCV infection is less common than HBV infection. However in the west, HCV (7.5m chronic carriers in the seven major markets) is more common than HBV. Historically this has been due to transmission through contaminated blood or blood products and is currently a result of shared utensils used for intravenous drug use.

 Recently completed research by independent market analyst Datamonitor** has revealed that despite increasing HBV and HCV disease awareness and diagnosis, treatment rates of patients with chronic viral hepatitis remain low, and despite the large pool of CHB and CHC patients, less than one-third of these are currently receiving medical treatment. One underlying reason is the low rate of disease diagnosis, on average 54% for HBV and 40% for HCV, says Datamonitor infectious diseases analyst Brigitte de Lima. “Chronic liver disease (CLD) is a long-term consequence of HBV and HCV and commonly leads to liver cirrhosis or hepatic decompensation within 10-40 years following primary infection.”

 “Furthermore, long-term CHB and CHC cause a type of liver cancer known as hepatocellular carcinoma (HCC). Both diseases combined account for over 80% of HCC cases and almost half a million lives annually. Once diagnosed, prognosis for HCC can be as low as six to eight months.”

 Diagnosis and treatment – still sub-optimal in the seven major markets

 Although HCV diagnosis rates are lower than those for HBV, they have increased considerably in the past two years, while those for HBV have remained flat. Key to the enhanced identification of new patients among both high-risk groups and the general population has been education and awareness campaigns organized by both the private and the public sector, de Lima says.

 “In addition to the low rates of diagnosis, inadequate therapies also account for the sub-optimal treatment levels. Although up to 80% of CHC patients with the easy-to-treat viral genotypes 2 and 3 can currently be cured, the larger prevalence of the less responsive genotype 1 translates into only half of the total patient pool achieving virus eradication.”

 “In the case of CHB the scenario is even worse, with viral eradication occurring in less than 5% of all patients. Current CHB therapy therefore focuses on long-term suppression of virus replication rather than virus clearance. Similar to CHC, the proportion of patients less responsive to treatment, namely those infected with the HBeAg-negative variant of HBV, is increasing globally.”

 Sub-optimal current first-line therapies for CHB and CHC are unable to benefit the already predominant and increasing pools of difficult-to-treat patients, leaving ample scope for opportunistic manufacturers willing to invest in potent, tolerable drugs in a market largely driven by therapy cost, de Lima says.

 Prescription choice – largely driven by cost-considerations

 The pharmaceutical HBV market is currently dominated by two antivirals, GlaxoSmithKline (GSK)’s Zeffix (lamivudine, LAM) and Gilead’s Hepsera (adefovir dipivoxil, ADV). Datamonitor’s research reveals that the preference of the former for first-line therapy is predominantly cost-driven, as the price of Zeffix is substantially lower than that of Hepsera, de Lima says. “ADV is commonly reserved for second-line therapy following the development of resistance to LAM, which can occur in up to 67% of patients after four years of therapy. For CHC, the standard of care is now pegylated interferon (pegIFN) and ribavirin (RBV) combination therapy.”

 “Similarly, the HCV market consists of two major players; Schering-Plough, who markets PegIntron and Rebetol, and Roche, with its drugs Pegasys and Copegus. The lack of clinical differentiation between the two rival pegIFNs and the absence of any alternative anti-HCV drugs has led to physician prescription choice being driven almost exclusively by cost and special deals provided by the manufacturers.”

 Current therapies – compromise is necessary

 Current therapies for either disease are far from being perfect solutions. None of the HBV drugs cure the disease and long-term therapy with LAM is associated with development of resistance, while ADV entails a high financial expenditure. Pegylated IFN combination therapy might be effective in some forms of CHC disease, but it is also a therapy dreaded by most patients due to the injectable mode of delivery and the high incidence of severe side effects elicited over the entire course of the treatment, de Lima says.

 “Given the clear limitations of the current HBV and HCV therapies, major players in both pharmaceutical markets have developed different strategies aimed at increasing treatment rates. In the case of CHC, these focus on treating patients with normal alanine aminotransferase (ALT) levels, prolonging treatment for slow responders and maintaining non-responders on pegIFN monotherapy. The main strategy for CHB patients is the extension of therapy, especially for HBeAg-negative patients, as most patients relapse following cessation of therapy.”

 The current stalemate in the CHB and CHC treatment markets is only susceptible to being broken with the launch of new developmental drugs, which will have to combine high potency and good tolerability at a reasonable cost. Crucially, new drugs are more likely to gain market share if, in addition to winning the battles against the more responsive variants of the diseases, they are also effective in the difficult-to-treat CHB and CHC patients. Drugs with high potency in the latter patients are the key to meeting the growing therapeutic needs and consequently boosting treatment rates, de Lima says.

 “The future viral hepatitis treatment landscape is predicted to follow the HIV precedent, in that drug monotherapy is likely to become obsolete and novel, potent drugs will be administered simultaneously as part of a combination. Furthermore, the focus needs to shift from patients with easily treatable variants of the disease to those that obtain little benefit from current therapies, as these are steadily accumulating in the total patient pools. New strategies are awaited to take the lead in this long-standing battle against the hepatitis viruses.”

 

 

 

 *The seven major pharmaceutical markets are the USA, the UK, France, Germany, Italy, Spain and Japan

 **Stakeholder Insight: Hepatitis B and C

 Datamonitor plc (DTM.L) is a premium business information company specialising in industry analysis. We help our clients, 5000 of the world's leading companies, to address complex strategic issues. Through our proprietary databases and wealth of expertise, we provide clients with unbiased expert analysis and in-depth forecasts for six industry sectors: Automotive, Consumer Markets, Energy, Financial Services, Healthcare, Technology. Datamonitor maintains its headquarters in London and has regional offices in New York, San Francisco, Sydney, Tokyo, Frankfurt, Shanghai and Hong Kong.

Posted by Ralph at 05:58 PM | Comments (0)

January 05, 2005

Hepatitis C With Fatty Liver Increases Risk

The following article comments on a study published in the January issue of the medical journal, Hepatology.

It starts out saying that the usefulness of antiviral therapy in patients with mild Hepatitis C is debatable. This indicates that the degree of steatosis in Hepatitis C patients should be one of the metrics in deciding on proceeding with interferon combination therapy.

Again, doctors will tend to prescribe therapy to 100% of patients who present with chronic Hepatitis C (because it is the only medical treatment available to them). This study is one more that calls into question this approach. Assessment of risk/reward ratio before proceeding with therapy needs to take this criterion into consideration, as well as others.

What is not stated in the author's conclusion is that they would not necessarily recommend antiviral therapy in patients with mild chronic Hepatitis C who do not present steatosis. Impact of Steatosis on the Progression of Fibrosis in Patients with Mild Hepatitis   

In patients with mild hepatitis C, the usefulness of antiviral therapy is a subject of debate, as a low risk for progression of fibrosis is assumed. Several studies have shown that steatosis (fatty liver) is a strong and independent predictor of the severity as well as the progression of fibrosis in chronic hepatitis C.

The present study assessed the impact of steatosis on the progression of fibrosis between paired liver biopsies in untreated patients with mild hepatitis on index biopsy.

One hundred thirty-five untreated patients (mean age, 38 years; M/F sex ratio, 1.43) with one known risk factor of infection (68 transfusions, 67 injecting drug use) had 2 liver biopsies after a median interval of 61 months (18-158). All had METAVIR score of A1F1 or lower at first liver biopsy.

Unequivocal progression of fibrosis was considered if patients had a fibrosis score of 3 or 4 at the second liver biopsy. The probability of progression of fibrosis was estimated by using the Kaplan-Meier method.

During follow-up, progression of fibrosis occurred in 21 patients (16%) after a median delay of 65 months. Cumulative probabilities of the progression of fibrosis at 4 and 6 years were 5.2% and 19.8%, respectively.

In multivariate analysis, steatosis was the only independent factor predictive of progression of fibrosis. Probability of progression of fibrosis was significantly related to the percentage of hepatocytes with steatosis.

The authors conclude, “Steatosis is a major determinant of the progression of fibrosis in mild hepatitis C, regardless of the genotype. Our results argue for antiviral treatment in the subgroup of patients with mild hepatitis and steatosis.”

01/05/05

Reference
L Fartoux and others. Impact of steatosis on progression of fibrosis in patients with mild hepatitis. Hepatology 41(1): 82-87. January 2005.

Posted by Ralph at 01:34 PM | Comments (0)

December 16, 2004

The "Other" Hepatitis and Hepatitis C

The following article is from the Conway Daily Sun. It is quite instructive for all hepatitis patients.

If high fat and alcohol can cause the sorts of liver problems mentioned in otherwise healthy people, then how much more important is it for chronic viral hepatitis people to keep these factors under control.

The bottom line is what I have been recommending for years. Regardless of what other approach you take to dealing with your condition, eat a whole foods balanced diet and do not drink alcohol.

Incidentally, milk thistle in general (and Maximum Milk Thistle in particular) has been shown to help maintain, protect and support a healthier liver, regardless of the condition. It has even been shown in laboratory testing to help regenerate healthy liver cells. Read more...

The Other Hepatitis
Dr. Brian Irwin

— Hepatitis literally means "inflammation of the liver." There are many causes of hepatitis. Quite often when they hear the term, most people immediately think of hepatitis caused by a series of viruses. Over time, an increasing number of viruses that cause liver inflammation have been identified and have been named accordingly. Hepatitis A. Hepatitis B. Hepatitis C, which, until fairly recently, was named "Hepatitis non-A, non-B." Delta hepatitis. The list goes on.

However as well known as these famous viruses are, they cause a proportionally small number of hepatitis cases in the Western Hemisphere. What is responsible for much more liver disease and subsequently death in the western world, and particularly in the United States, is fat.

By fat, I'm referring to accumulation of fat in the liver cells themselves. Triglycerides can, due to a number of causes, accumulate in the liver cells and ultimately cause inflammation, liver congestion and even liver failure. By far the most common cause of excess fat accumulation in liver cells is alcohol abuse. Excessive alcohol intake can damage the liver in a number of ways, but one of the known mechanisms is by excess fatty acid production that is a result of ethanol metabolism, and subsequent deposition of these acids in the liver.

Malnutrition alone can also cause this to occur, but unfortunately many heavy drinkers do not eat properly. Subsequently, these people suffer damage from their poor nutrition AND from their alcohol intake.

There are other causes for fat deposition in the liver. Other than alcohol, the most common cause in this country is a high-fat diet. The liver performs the function of "detoxifying" the bloodstream. The liver produces the enzymes and a material (called bilirubin) that is required to "dissolve" fat, help metabolize it and store or excrete it.

A tremendously high concentration of triglycerides can easily overwhelm the system, back up and regurgitate into the liver cells proper. The result is slow, but steady liver damage that can, eventually, become irreversible.

The recent documentary "Supersize ME" showed the effects of a fat- and sugar-rich diet on a previously healthy person. One of the major changes in this previously healthy subject's condition was his liver function. The subject of the film experienced an increase in his "Liver Function Tests," which are a series of tests that measure enzyme production by liver cells. These "LFT?s" are increased in almost all cases of inflammation; quite literally the subject of the film, by diet alone, gave himself hepatitis.

So what happens if you ignore hepatitis, fatty or alcoholic? Hepatitis can be with or without symptoms and, quite often, is a diagnosis that health-care providers "stumble" upon by finding incidentally elevated LFTs. Symptoms can range from painless jaundice (yellowing of the skin that occurs as bilirubin, one of the products of the liver, "spills over" into the bloodstream and deposits in the skin), to nausea, vomiting, atrophy of the testicles, hair loss or a whole host of other symptoms.

More concerning, perhaps, than the health ramifications of hepatitis are the health ramifications of chronic hepatitis....cirrhosis. Cirrhosis is the end-stage result of hepatitis. A liver with chronic inflammation will eventually scar, shrink up and eventually stop working. At this point severe fluid accumulation, severe mental status changes (confusion, seizures or coma), infection, bleeding tendencies and cancer can all present.

As ominous as all this sounds, there is good news. Not all cases of hepatitis progress to cirrhosis. Although not all kinds of hepatitis are reversible, most cases of fatty liver caused by increased fat intake or excess alcohol will revert to normal or near-normal liver function...IF the offending agent is removed! While health-care providers can't promise all cases will totally revert to normal, we can promise that if a patient has fatty liver disease and hepatitis, if lifestyle changes aren't instituted, that patient's liver will progress to failure.

Of course, there is a genetic component to liver disease. Some people can eat a very high fat diet and never develop fatty hepatitis. Some people drink eight drinks every day and never have a problem. However, others can develop fatty liver disease from a relatively small amount of dietary fat and triglycerides or only a modest alcohol intake history.

This doesn't mean everyone should be on a no-fat diet or that no one should ever have a glass of wine. What it does mean is that at this time there's no way to tell who will luck out and who won't. Some of us are more susceptible to liver disease than others, so to be safe, eat right, take everything, not just alcohol and fat, in moderation and if you ever have any questions ask your health-care provider for

Posted by Ralph at 10:24 AM | Comments (0)

December 03, 2004

Blood Tests vs. Biopsy For Fibrosis Assessment

This reference is from an article in the latest issue of the medical journal, Gastroenterology.

What we found most interesting is the reference to the fact that biopsy can be painful and dangerous and that assessment of biopsies is subjective and prone to sampling error. So much for accuracy in the gold standard test for gauging liver condition.

More and more progress is being made with blood and serum tests to determine fibrosis progression and liver condition. This bodes very well for keeping an eye on liver disease progress without invasive and potentially dangerous or faulty biopsies.

Our only question is why the authors concluded this could or should be used in conjunction with biopsy. We feel "instead of" may be a better choice.

Serum Markers Detect the Presence of Liver Fibrosis

Histologic examination of a liver biopsy specimen is regarded as the reference standard for detecting liver fibrosis. Biopsy can be painful and hazardous, and assessment is subjective and prone to sampling error.

Researchers developed a panel of sensitive automated immunoassays to detect matrix constituents and mediators of matrix remodeling in serum to evaluate their performance in the detection of liver fibrosis.

In an international multicenter cohort study, serum levels of 9 surrogate markers of liver fibrosis were compared with fibrosis stage in liver biopsy specimens obtained from 1021 subjects with chronic liver disease.

Discriminant analysis of a test set of samples was used to identify an algorithm combining age, hyaluronic acid, amino-terminal propeptide of type III collagen, and tissue inhibitor of matrix metalloproteinase 1 that was subsequently evaluated using a validation set of biopsy specimens and serum samples.

Results

The algorithm detected fibrosis (sensitivity, 90%) and accurately detected the absence of fibrosis (negative predictive value for significant fibrosis, 92%);

Performance was excellent for alcoholic liver disease and nonalcoholic fatty liver disease.

The algorithm performed equally well in comparison with each of the pathologists.

In contrast, pathologists’ agreement over histologic scores ranged from very good to moderate.

Conclusions

The authors conclude, “Assessment of liver fibrosis with multiple serum markers used in combination is sensitive, specific, and reproducible, suggesting they may be used in conjunction with liver biopsy to assess a range of chronic liver diseases.”

12/03/04

Reference
W M C Rosenberg and others. Serum markers detect the presence of liver fibrosis: A cohort study. Gastroenterology 127(6): 1704-1713. December 2004.

Posted by Ralph at 06:38 PM | Comments (0)

November 27, 2004

Another Biopsy Alternative For Hepatitis C Patients

It seems doctors all want to do biopsies for liver patients, especially with Hepatitis C. In order to undergo interferon therapy doctors insist on a biopsy first.

Until recently there was no other way to get an exact measurement of fibrosis progression. We have already reported on a few blood tests that are currently approved for measuring fibrosis instead of undergoing a biopsy. One is Fibrospect and another is FibroTest.

Now, there is a report of yet another way to assess fibrosis without sticking a needle through your abdomen and into your liver.

This is great news for hemopheliacs and those of us who prefer to avoid the possible negative side effects of a biopsy (bleeding into the abdomen, liver damage, etc.).

Non-invasive Assessment of Liver Fibrosis by Liver Stiffness Measurement (LSM) in HCV Patients

Despite limitations such as sampling error and risks of complications, liver biopsy remains the gold standard for assessment of liver fibrosis. Among alternative non invasive methods, LSM based on transient elastography appears promising.

The purpose of this study was to investigate in comparison with histological staging in patients with chronic hepatitis C (CHC) focusing on patients with the largest liver biopsy samples.

French researchers prospectively included 327 patients with CHC who underwent both liver biopsy and LSM in four centers. LSM was performed with the FibroScan (Echosens Co, Paris, France) a non invasive device measuring liver stiffness in a volume of parenchyma of about 1,5 cm3.

In order to minimize the bias of histological evaluation, fibrosis stage was assessed according to METAVIR classification by two experienced pathologists. Moreover, biopsies were selected to have at least ten portal tracts or obvious cirrhosis.

The studied population was then split into two groups according to the biopsy sample length: biopsy sample larger than the median size (18 mm for F01, F2 and F3 patients and 13 mm for F4 patients) were considered separately.

Taking into account the whole studied population, LSM was significantly correlated with fibrosis stage (Kendall tau beta coefficient of correlation: 0.55, p < 0.0001) and the area under the ROC curves was 0.79 for F ≥ 2, 0.91 for F ≥ 3 and 0.97 for F = 4. These values were even improved when only the largest biopsies were considered: 0.81 for F ≥ 2, 0.95 for F ≥ 3 and 0.99 for F = 4.

The authors conclude, “LSM is a reliable, non invasive method for the evaluation of liver fibrosis in patients with CHC. The volume of liver parenchyma explored obviates the risk of sampling error present in liver biopsy.”

11/24/04
Reference
M Ziol and others. NON INVASIVE ASSESSMENT OF LIVER FIBROSIS BY LIVER STIFFNESS MEASUREMENT (LSM) IN PATIENTS WITH CHRONIC HEPATITIS C (CHC): THE IMPORTANCE OF SAMPLING. Abstract 263 (poster). 55th AASLD. October 29-November 2, 2004. Boston, MA.

Posted by Ralph at 03:22 PM | Comments (0)

November 23, 2004

Hepatitis C and Quality of Life

The following article is about quality of life issues with Hepatitis C patients.

It is our opinion that anyone who knows they have a chronic and potentially deadly disease is going to have a negatively affected quality of life. Fear, anxiety, concerns about debilitating illness and mortality all take a toll on a persons outlook on life.

People infected prior to age 25, as well as male gender, seem to be the only factors that predicted a lesser impact on quality of life for Hepatitis C patients.

To make the leap of logic in the conclusion of this report that even those with little or no liver damage should consider anti viral therapy left us a bit incredulous. What pharmaceutical company funded this study, anyway?

Did the authors not consider the impact of interferon therapy on QoL (at least during therapy)? And, what of the other important factors, like a 30% success rate for genotype 1? Shouldn't that figure into the equation?

Food for thought, no?

The Quality of Life Among Patients with Chronic Hepatitis C in Relation to Host and Viral Factors

There is increasing evidence for impaired Quality of life (QoL) in patients with hepatitis C virus (HCV) infection even in the absence of liver disease. The aim of the study was to discriminate the role of viral and host factors in regard to QoL.

A cohort of 630 patients initially recruited in 1996/1997 in eight European Hepatology Centers to analyse epidemiology and immunogenetics of HCV infection were followed in 2002/2003. All patients answered an SF-36 questionnaire for the assessment of their QoL.

Two summary scores were analysed: the Physical Component Score (PCS) and the Mental Component Score (MCS). These patients are representative of what is usually seen in clinical practice since no restriction was made at inclusion.

Results

Patients with sustained virological response showed significantly better QoL than patients with either relapse or non-response (p<0.001 and p=0.001, for MCS and PCS respectively), even when limited to patients with only minimal fibrosis (F<2), p=0.001 for PCS.

An association was also found with age at infection and sex. Patients younger than 25 years at infection and males showed better PCS (p<0.001 and p=0.008) and MCS (p=0.063 and p=0.002), respectively.

None of the HLA alleles tested showed any association with QoL. Likewise genotype 1a vs. 1b or genotype 1 vs. non-1 had no significant relevance.

Conclusion

The authors conclude, “The better quality of life in patients with sustained virological response indicates that antiviral therapy might even be indicated in the absence of any liver disease.”

11/22/04
Reference
H L Tillmann and others (for the HENCORE group). QUALITY OF LIFE IN HEPATITIS C PATIENTS IN RELATION TO HOST AND VIRAL FACTORS. Abstract 1207 (poster). 55th AASLD. October 29-November 2, 2004. Boston, MA.

Posted by Ralph at 11:14 AM | Comments (2)

November 17, 2004

Hepatitis C and Fatigue

We have long noted the number one complaint of chronic Hepatitis c patients is fatigue. The following study, presented at the latest AASLD conference in Boston, verifies this observation.

Currently there is no real medical solution to the fatigue felt by Hepatitis c patients. The best natural fatigue intervention we have seen, to date, is Fatigue Relief Plus (http://www.fatiguerelief.com).

If you can relate to the information in this study, perhaps you should consider giving Fatigue Relief Plus a try. It has worked for others, it very well may work for you.

Sleep and Fatigue in Patients with Chronic Hepatitis C

Fatigue and disordered sleep have been shown to affect quality of life in patients with chronic illnesses. The purpose of this study was to evaluate fatigue and sleeping behavior reported by patients with Chronic Hepatitis C (CHC).

Subjects completed the Fatigue Severity Scale (FSS) resulting in a total average fatigue score derived from 9 Likert type scale items assessing disabling fatigue (range 1-7). Subjective sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI) in which a global score (ranging from 0-21) and 7 component scores were derived. In both cases a high score indicated more severe complaints.

Subjects were 59 CHC patients attending UCSD Adult Liver Clinics who completed both the FSS and PSQI questionnaires. CHC patients were 49% males, 57.6% Caucasian, 35.6% Latino, and 3.4% African-American. Mean age and education were 51.9 ± 9.18 and 12.4 ± 3.31 years respectively. 24 patients were non-cirrhotic, 31 were cirrhotic (Child-Turcotte-Pugh Score A=16, B=11, C=3, 1-unknown), and 4 were unknown. No patients were receiving antiviral therapy at the time of assessment.

Results

The mean FSS score was 4.69 ± 1.88 indicating greater fatigue than past reports of normal healthy adults (2.3) and patients with CHC (3.8). The mean PSQI global score was 8.97 ± 5.38.

64.4% of the patients were found to be ‘poor sleepers’ as defined by a global PSQI score of > 5. There was no significant difference between males and females on both measures.

Significant correlations were found between the FSS score and the global PSQI score (r=0.58, p < 0.01), and with 6 of the PSQI component scores: subjective sleep quality (r=0.46, p < 0.01), sleep latency (r=0.39, p < 0.01), sleep duration (r=0.26, p = 0.05), habitual sleep efficiency (r=0.44, p < 0.01), sleep disturbances (r=0.62, p < 0.01), and daytime dysfunction (r=0.65, p < 0.01).

There were no significant differences between cirrhotic and non-cirrhotic patients on the FSS and PSQI global score. Poor sleepers were 51.6% and 75% of the cirrhotic and non-cirrhotic patients respectively (p=0.10). Non-cirrhotic patients showed greater use of sleeping medications when compared to cirrhotic patients (p < 0.01).

Weekly use of sleeping medications was reported in 33% of non-cirrhotic versus 9.7% of cirrhotic patients.

In conclusion, the authors write:

(1) Patients with CHC suffer from poor quality of sleep regardless of their stage of liver disease.

(2) Fatigue is significantly correlated to poor sleep quality.

11/17/04

Reference
M 55th AASLD. October 29-November 2, 2004. Boston, MA.Carlson and others. SLEEP AND FATIGUE IN PATIENTS WITH CHRONIC HEPATITIS C. Abstract 19 (poster).

Posted by Ralph at 01:49 PM | Comments (0)

October 22, 2004

Hepatitis C Virus Linked to Non-Hodgkins Lymphoma

The following release is interesting but, unfortunately, not very detailed. The researchers give no numbers to put their findings into perspective. I'll try to help.

In 1991, 15 people per 100,000 were likely to contract NHL. If HCV patients are 6 times more likely to contract NHL then that means 90 HCV patients out of 100,000 might contract NHL.

90 people out of 100,000 (or about one in a thousand) is certainly no cause for panic, but instead something HCV patients and their doctors should be aware of.

SEATTLE--Patients infected with the hepatitis C virus (HCV) are six times as likely to develop non-Hodgkin's lymphoma (NHL) than individuals that are virus free, according to research presented today at the Third Annual Frontiers in Cancer Prevention Research meeting.

HCV infected patients have a seventeen fold higher risk for developing diffuse large B-Cell lymphoma, researchers from British Columbia documented. Diffuse large B-cell lymphoma is the most common variety of NHL, comprising approximately 30 percent of all NHL patients.

Compared to Europe and Japan, incidence of hepatitis C viral infection is fairly low in North America, and previous studies from Canada and the United States have not shown an association between the virus and development of NHL, said Ms Agnes Lai, lead author for the research. The British Columbia study examined HCV status in 550 NHL cases and 205 population controls. The study had the strength of numbers of patients to ascertain an association between HCV and NHL, confirming the viral-cancer link suspected in studies from other areas of the world where the virus is more prevalent.

"People who have been exposed to the virus comprise a high risk group for developing non-Hodgkin's lymphoma, particularly diffuse b-cell lymphoma," said John Spinelli, a cancer researcher from the British Columbia Cancer Agency, Vancouver, BC, and principal investigator of the research study.

The spread of hepatitis C in the United States has dropped significantly since the 1980s. Currently, the number of new cases per year is around 25,000. Approximately 3.8 million Americans have been infected with the virus. The most common means of infection in the past was blood transfusion, and in recent years is among drug users who share needles.

Approximately 53,000 patients were diagnosed with NHL in the United States in 2003. There were 23,000 deaths from the disease that year.

Spinelli and Lai conducted their research with colleagues Randy Gascoyne, Joseph Connors, Pat Lee, Rozmin Janoo-Galani, and Richard Gallagher, BC Cancer Agency; Anton Andonov, Health Canada National Microbiology Laboratories, Winnipeg, Manitoba, and Darrel Cook, British Columbia Centre for Disease Control.

Posted by Ralph at 02:44 PM | Comments (0)

October 19, 2004

Retreatment of Non-Responders

According to this article, retreatment is not a very viable strategy in most cases of a failed first attempt to eradicate the virus with interferon therapy. This repeat approach only seems somewhat successful with people who were not treated with combination therapy to begin with.

It seems only some of those who received monotherapy (before the combo was developed) really have any chance of success with this subsequent combo treatment. And, only if they are not genotype 1, have a low viral load, do not have cirrhosis.

Reading between the lines here also reinforces our belief that the success rates being tossed about by doctors are misleading. This article states that nearly half do not respond. If this includes all genotypes then the higher rate for genotype 2 (supposedly around 80%) is clearly being reduced by the lower rate for genotype 1 (supposedly around 50% but more likely less than 30% to arrive at the "nearly half" statement). With 70% of the US chronic Hepatitis C having genotype 1, this is significant.

Retreatment of Non-Responders

Despite improvements in the treatment of chronic hepatitis C virus (HCV) infection, nearly half of all patients do not respond to initial therapy.

Retreatment of these patients with pegylated interferon and ribavirin has been successful in only a limited percentage of cases.

Factors associated with sustained virologic response (SVR) following retreatment include prior treatment with interferon monotherapy, HCV genotype 2 or 3, a low serum HCV RNA level, and the absence of cirrhosis.

Fewer than 6% of nonresponders who were previously treated with interferon and ribavirin and who have cirrhosis, genotype 1, and a high viral load achieve SVR following retreatment with pegylated interferon and ribavirin.

No therapy has been shown to yield SVR in patients who do not respond to pegylated interferon and ribavirin.

Long-term maintenance therapy with pegylated interferon is currently being evaluated in nonresponders with advanced fibrosis and cirrhosis. Its use should be considered investigational at this time.

Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA.

10/18/04

Reference
M L Shiffman. Retreatment of patients who do not respond to initial therapy for chronic hepatitis C. Cleveland Clinical Journal of Medicine 71 (Suppl 3): S13-16. May 2004.

Posted by Ralph at 12:06 PM | Comments (0)

October 18, 2004

Hepatitis C and Sex

One of the most frequent questions I hear from newly diagnosed Hepatitis c patients is whether or not they could pass this disease on to their loved ones through sexual intercourse. I am also frequently contacted by people in relationship with Hepatitis c patients. They have heard the disease was sexually transmitted and are afraid of contracting it themselves.

There has been much confusion and misinformation about this subject out there. Even the Centers for Disease Control (CDC) website states that sexual transmission is possible (although unlikely).

This new study (cited below) basically proves once and for all that there is no real risk of sexual transmission as long as blood to blood contact is avoided. This is good news, and it also points to the wisdom of staying up to date with emerging knowledge about hepatitis c. More is being discovered and clarified about this disease on an ongoing basis. Even the smallest of these discoveries can directly impact our lives as hepatitis c patients.

Incidenally, this finding does not mean you should be cavalier or nonchalant about the fact you have this infectious and potentially deadly disease. Sharing toothbrushes or razor blades are still considered risky activities. And high risk sexual behavior that might cause any blood to blood contact is to be rigorously avoided. To be safe, be sensible.

No Evidence of Sexual Transmission of Hepatitis C among Monogamous Couples: Results of a 10-Year Prospective Study

The risk of sexual transmission of hepatitis C virus (HCV) infection was evaluated among 895 monogamous heterosexual partners of HCV chronically infected individuals in a long-term prospective study, which provided a follow-up period of 8,060 person-years. Seven hundred and seventy-six (86.7%) spouses were followed for 10 yr, corresponding to 7,760 person-years of observation.

One hundred and nineteen (13.3%) spouses (69 whose infected partners cleared the virus following treatment and 50 who ended their relationship or were lost at follow-up) contributed an additional 300 person-years.

All couples denied practicing anal intercourse or sex during menstruation, as well as condom use. The average weekly rate of sexual intercourse was 1.8.

Three HCV infections were observed during follow-up corresponding to an incidence rate of 0.37 per 1,000 person-years. However, the infecting HCV genotype in one spouse (2a) was different from that of the partner (1b), clearly excluding sexual transmission.

The remaining two couples had concordant genotypes, but sequence analysis of the NS5b region of the HCV genome, coupled with phylogenetic analysis showed that the corresponding partners carried different viral isolates, again excluding the possibility of intra-spousal transmission of HCV.

The authors conclude, “Our data indicate that the risk of sexual transmission of HCV within heterosexual monogamous couples is extremely low or even null. No general recommendations for condom use seem required for individuals in monogamous partnerships with HCV-infected partners.”

Posted by Ralph at 10:22 AM | Comments (0)

October 01, 2004

Hepatitis Treatment Options

What Is the Best Treatment for Chronic Hepatitis C?

The treatment of hepatitis C is expensive, difficult and arduous from the patient's perspective. It is similarly difficult for the clinician to decide who and when to treat.

What Is the Best Treatment for Chronic Hepatitis C?

By JF Dillon, MD

The treatment of hepatitis C is expensive, difficult and arduous from the patient's perspective. It is similarly difficult for the clinician to decide who and when to treat.

If hepatitis C is viewed from the liver's perspective, we need only treat those patients who will develop the complications of chronic liver disease within their lifetimes. If we take a more holistic approach, then we have to consider the implications of being a carrier of a potentially transmissible blood borne virus on the patient themselves, their relationships, their families and their sense of well-being.

There is now evidence of the large impact HCV has on quality of life and we have to consider extra hepatic manifestations of hepatitis C infection, possibly including the syndrome of brain fog recently described.

An additional factor that has to be considered in the decision to treat is whether patients perceive hepatitis C as a significant problem for themselves.

For some patients, who have chaotic live styles, it is extremely difficult to get them to access healthcare. To then undergo the rigors and tribulations of hepatitis C therapy that is posing no current problem is unlikely to succeed.

However, failure to engage these patients with therapy will lead to a significant proportion of them presenting with serious complications of chronic liver disease, with its attendant mortality, morbidity and cost.

Underlying all these considerations is the tension between the costs of therapy and the benefits of therapy.

The author concludes, Good arguments can be made in terms of cost-effectiveness for treating patients with a high likelihood of progressing to chronic liver disease and its complications. These arguments become much less persuasive when all patients are concerned.

Department of Digestive Diseases and Clinical Nutrition, Ninewells Hospital and Medical School, Dundee, UK.

09/20/04
Reference
J F Dillon. What is the best treatment for Chronic Hepatitis C? Journal of Viral Hepatitis 11 Suppl 1:23-27. September 2004.

Posted by Ralph at 12:44 PM | Comments (0)