MEDICAL TESTS AND PROCEDURES.

LIVER BIOPSY

Before treatment for chronic Hepatitis B and to assess the progress of the disease it is generally recommended to have a liver biopsy as this is currently the only way to accurately assess the course of the disease and if the liver is found to have advanced cirrhosis or is decompensated then interferon or/and other treatments should be used with caution or not used.

WHAT IS A LIVER BIOPSY?

Liver biopsy is a diagnostic procedure used to obtain a small amount of liver tissue, which can be examined under a microscope to help identify the cause or stage of liver disease.

WHAT ARE THE DIFFERENT WAYS LIVER BIOPSY CAN BE PERFORMED?

The most common way a liver sample is obtained is by inserting a needle into the liver for a fraction of a second. This can be done in the hospital, and the patient may be sent home within 3-6 hours if there are no complications. The physician determines the best site, depth, and angle of the needle puncture by physical examination or ultrasound. The skin and area under the skin is anaesthetised, and a needle is passed quickly into and out of the liver. Approximately half of individuals have no pain afterwards, while another half will experience brief localised pain that may spread to the right shoulder.

Another technique used for liver biopsy is guiding the needle into the liver through the abdomen or chest using various imaging techniques. This approach is used when there are localised tumours identified by ultrasound or computed tomography (CT). Either ultrasound or CT scanning is used to pinpoint the site of the tumour and guide the needle to this specific area through the abdomen or chest. After this procedure, the patient is usually allowed to go home the same day.

Less commonly used biopsy techniques are laparoscopy, transvenous or transjugular liver biopsy, and surgical liver biopsy.

With laparoscopy, a lighted, narrow tubular instrument is inserted through a small incision in the abdominal wall. The internal organs are moved away from the abdominal wall by gas that is introduced into the abdomen. Instruments may be passed through this lighted instrument or through separate puncture sites to obtain tissue samples from several different areas of the liver. Patients who undergo this procedure may be discharged several hours later.

Transvenous or transjugular liver biopsy may be performed by a radiologist in special circumstances, e.g. when the patient has a significant problem with blood clotting (coagulopathy) or a large amount of fluid within the abdomen (ascites). With this procedure, a small tube is inserted into the internal jugular vein in the neck and radiologically guided into the hepatic vein, which drains the liver. A small biopsy needle

is then inserted through the tube and directly into the liver to obtain a sample of tissue.

Finally, liver biopsy may be done at the time a patient undergoes an open abdominal operation, enabling the surgeon to inspect the liver and take one or more biopsy samples as needed.

WHEN IS A LIVER BIOPSY USED?

Liver biopsy is often used to diagnose the cause of chronic liver disease that results in elevated liver tests or an enlarged liver. It is also used to diagnose liver tumours identified by imaging tests. In many cases the specific cause of the chronic liver disease is highly suspected on the basis of blood tests, but a liver biopsy is used to confirm the diagnosis as well as determine the amount of damage to the liver. Liver biopsy is also used after liver transplantation to determine the cause of elevated liver tests and determine if rejection is present.

WHAT ARE THE DANGERS OF LIVER BIOPSY?

The primary risk of liver biopsy is bleeding from the site of needle entry into the liver, although this occurs in less than 1% of patients. Other possible complications include the puncture of other organs, such as the kidney, lung or colon. Biopsy, by mistake, of the gallbladder rather than the liver may be associated with leakage of bile into the abdominal cavity, causing peritonitis. Fortunately, the risk of death from liver biopsy is extremely low, ranging from 0.1% to 0.01%.

ARE THERE ALTERNATIVES TO LIVER BIOPSY?

The primary alternative to a liver biopsy is to make the diagnosis of a liver disease based on the physical examination of the patient, medical history, and blood testing. In some cases, blood testing is quite accurate in giving the doctor the information to diagnose chronic liver disease, while in other circumstances a liver biopsy is needed to assure an accurate diagnosis.

DO LIVER BIOPSIES EVER NEED TO BE REPEATED?

In most circumstances, a liver biopsy is only performed once to confirm a suspected diagnosis of chronic liver disease. Occasionally, liver biopsy is repeated if the clinical condition changes or to assess the results of medical therapy, such as drug treatment of chronic viral hepatitis with interferon or prednisone therapy of autoimmune hepatitis. Patients who have undergone liver transplantation often require numerous liver biopsies in the early weeks to months following the surgery to allow accurate diagnoses of whether the new liver is being rejected or whether other problems have developed.

BIOPSY RESULTS.

After a few weeks they will have the result of your biopsy. Try to listen very carefully to what the doctor tells you, it may sound like gibberish but make notes then you can ask questions of your doctor, look things up in books ask on the support group etc later when you've had a chance to digest things.

Ask your doctor if you can have a copy of your biopsy results for reference. If the biopsy was for Hepatitis B infection depending on the results of the biopsy they may suggest you take interferon.

WHAT DO I NEED TO DO IF I'M HAVING A BIOPSY.

If your nervous about it ask your doctor for some valium or similar to take the night before and the morning before you go in (make sure the doctor doing the biopsy and the nurses looking after you knows if you've taken anything), also it's a good idea to have someone pick you up from the hospital.

The procedure is simple, you lie on your side and a local anaesthetic is administered. A needle is inserted between your ribs and a core of liver tissue is removed. This is normally painless however some people get a pain in the right shoulder. After the biopsy you must lie on your side for about 4 hours to help stop any bleeding and your blood pressure is taken, If you need pain killers ask for them. After this you can normally leave the hospital. When at home you should take it easy for the first week, generally sitting and sleeping to apply some pressure to the side with cushions or pillows as this aids healing, helps prevent bleeding and may be more comfortable . For 14 days after the biopsy you should remain within one hour of a major hospital and you should ensure the people with you know, or you should carry information to alert medical staff that you have recently had a biopsy.

LIVER FUNCTION TESTS (LFT'S)

A blood sample is taken, normally from the arm and sent to the laboratory for analysis and results are normally available with a few days.

The term "liver function tests" and its abbreviated form "LFT's" is a commonly used term that is applied to a variety of blood tests that assess the general state of the liver and biliary system. Routine blood tests can be divided into those tests that are true LFT's, such as serum albumin or prothrombin time, and those tests that are simply markers of liver or biliary tract disease, such as the various liver enzymes. In addition to the usual liver tests obtained on routine automated chemistry panels, physicians may order more specific liver tests such as viral serologic tests or autoimmune tests that, if positive, can determine the specific cause of a liver disease. Liver function tests measure various chemicals present in the blood and can be useful in determining the extent of liver disease.

There are two general categories of "liver enzymes." The first group includes the alanine aminotransferase (ALT) and the aspartate aminotransferase (AST), formerly referred to as the SGPT and SGOT. These are enzymes that are indicators of liver cell damage. The other frequently used liver enzymes are the alkaline phosphatase and gamma-glutamyltranspeptidase (GGT and GGTP) that indicate obstruction to the biliary system, either within the liver or in the larger bile channels outside the liver.

ALT OR SGPT

FROM - FOCUS: ON HEPATITIS C

ALT, an enzyme appears in liver cells, with lesser amounts in the kidneys, heart, and skeletal muscles, and is a relatively specific indicator of acute liver cell damage. When such damage occurs, ALT is released from the liver cells into the bloodstream, often before jaundice appears, resulting in abnormally high serum levels that may not return to normal for days or weeks.

The purpose of this blood serum test is to help detect and evaluate treatment of acute hepatic disease, especially hepatitis, and cirrhosis without jaundice. To help distinguish between mytyocardial (heart) and liver tissue damage (used with the AST enzyme test). Also to assess hepatotoxicity of some drugs.

ALT levels by a commonly used method range from 10 to 32 U/L; in women, from 9 to 24 U/L. (There does exist differing ranges used by various laboratories.) The normal range for infants is twice that of adults.

Very high ALT levels (up to 50 times normal) suggest viral or severe drug-induced hepatitis, or other hepatic disease with extensive necrosis (death of liver cells). (AST levels are also elevated but usually to a lesser degree.) Moderate-to-high levels may indicate infectious mononucleosis, chronic hepatitis, intrahepatic cholestasis or cholecystitis, early or improving acute viral hepatitis, or severe hepatic congestion due to heart failure. Slight-to-moderate elevations of ALT (usually with higher increases in AST levels) may appear in any condition that produces acute hepatocellular (liver cell) injury, such as active cirrhosis, and drug-induced or alcoholic hepatitis. Marginal elevations occasionally occur in acute myocardial infarction (heart attack), reflecting secondary hepatic congestion or the release of small amounts of ALT from heart tissue.

Many medications produce hepatic injury by competitively interfering with cellular metabolism. Falsely elevated ALT levels can follow use of barbiturates, narcotics, methotrexate, chlorpromazine salicylates (aspirin), and other drugs that affect the liver.

Be Aware: Serum liver enzymes can create confusion for both patients and physicians for these tests are highly sensitive, but very non-specific. Tests commonly referred to as liver function tests or LFT's do not actually determine liver function. Instead, they are static, primarily diagnostic parameters that serve to detect liver disease rather than quantitative liver function. Rather than liver function tests, it is more useful to refer to these tests as serum liver tests and to mentally categorise them according to the pathophysiologic processes they truly reflect.

AST

One of the two main liver function blood serum tests (the other being the ALT test). The purpose of this blood test is to detect a recent myocardial infarction (heart attack); to aid detection and differential diagnosis of acute hepatic disease and to monitor patient progress and prognosis in cardiac and hepatic diseases. AST levels by a commonly used method range from 8 to 20 U/L although some ranges may express a maximum high in the 40s. (Check with your physician.)

AST levels fluctuate in response to the extent of cellular necrosis (cell death) and therefore may be temporarily and minimally elevated early in the disease process, and extremely elevated during the most acute phase. Depending on when the initial sample was drawn, AST levels can rise- indicating increasing disease severity and tissue damage- or fall- indicating disease resolution and tissue repair. Thus, the relative change in AST values serves as a reliable monitoring mechanism.

Maximum elevations are associated with certain diseases and conditions. For example, very high elevations (more than 20 times normal) may indicate acute viral hepatitis, severe skeletal muscle trauma, extensive surgery, drug-induced hepatic injury, and severe liver congestion. High levels (ranging from 10 to 20 times normal) may indicate severe myocardial infarction (heart attack), severe infectious mononucleosis, and alcoholic cirrhosis. High levels may also occur during the resolving stages of conditions that cause maximal elevations. Moderate-to-high levels (ranging from 5 to 10 times normal) may indicate chronic hepatitis and other conditions. Low-to-moderate levels (ranging from 2 to 5 times normal) may indicate metastatic hepatic tumours, acute pancreatitis, pulmonary emboli, alcohol withdrawal syndrome, and fatty liver (steatosis).

BILIRUBIN

Bilirubin is the main bile pigment in humans which, when elevated causes the yellow discoloration of the skin and eyes called jaundice. Bilirubin is formed primarily from the breakdown of a substance in red blood cells called "heme." It is taken up from blood processed through the liver, and then secreted into the bile by the liver. Normal individuals have only a small amount of bilirubin circulating in blood (less than 1.2 mg/dL). Conditions which cause increased formation of bilirubin, such as destruction of red blood cells, or decrease its removal from the blood stream, such as liver disease may result in an increase in the level of serum bilirubin. Levels greater than 3 mg/dL are usually noticeable as jaundice. The bilirubin may be elevated in many forms of liver or biliary tract disease, and thus it is also relatively non-specific. However, serum bilirubin is generally considered a true test of liver function (LFT), since it reflects the liver's ability to take up, process, and secrete bilirubin into the bile.

GGT (GAMMA GLUTAMYLTRANSFERASE)

The purpose of this blood serum chemistry test is to provide information about hepatobiliary diseases, to assess liver function, and to detect alcohol ingestion. Another purpose is to distinguish between skeletal disease and hepatic disease when serum alkaline phosphatase is elevated. A normal GGT level suggests such elevation stems from skeletal disease.

Normal results in females under age 45, range from 5 to 27 U/L; in females over age 45 and in males, levels range from 6 to 37 U/L. Serum GGT values vary with the assay method used (colorimetric or kinetic).

The sharpest increases in GGT levels indicate obstructive jaundice and hepatic metastasis. Elevations may indicate any acute hepatic disease, acute pancreatitis, renal disease, alcohol ingestion, postoperative status, and prostatic metastasis.

This test is non-specific, providing little data about the type of hepatic disease. GGT is particularly sensitive to the effects of alcohol in the liver, and levels may be elevated after moderate alcohol intake and in chronic alcoholism, even without clinical evidence of hepatic injury.

SERUM ALBUMIN

Albumin is a major protein which is formed by the liver, and chronic liver disease causes a decrease in the amount of albumin produced. Therefore, in liver disease, particularly more advanced liver disease, the level of the serum albumin is reduced (less than 3.5 mg/dL).

PROTHOMBIN TIME.

The prothrombin time, which is also called protime or PT, is a test that is used to assess blood clotting. Blood clotting factors are proteins made by the liver. When the liver is significantly injured, these proteins are not normally produced. The prothrombin time is also a useful LFT, since there is a good correlation between abnormalities in coagulation measured by the prothrombin time and the degree of liver dysfunction. Prothrombin time is usually expressed in seconds and compared to a normal control patient's blood.

PCR

This test uses the Polymerase Chain Reaction or PCR to amplify the amount of DNA or RNA present in a sample. The test is highly sensitive and can detect minute quantities of DNA or RNA. With regard to Hepatitis B the test comes in two forms:-

QUALITATIVE PCR

This test tests for the presence of Hepatitis B DNA, it is highly sensitive and gives a positive or negative result and is generally only used for research purposes. In someone who has never been exposed to Hepatitis B a negative result would occur. In those with acute or chronic Hepatitis B a positive result would be expected. In people who have successfully defeated a Hepatitis B infection and developed antibodies to the surface antigen a negative result would be expected, however many positive results have been reported and this indicates that the Hepatitis B virus is sometimes present, although in minute quantities, in those who have developed antibodies to the virus.

QUANTITATIVE PCR

This measures the quantity of Hepatitis B DNA present in a sample. It is not as sensitive as qualitative PCR but does give an indication of the number of copies of the virus present. This result is used to determine what is known as "viral load" or the number of copies of the virus present.

This test is relatively expensive and generally only used for research purposes as other Hepatitis B antigens can be used for diagnostic purposes. E.g. the presence of the "e" antigen indicates a high level of viral reproduction and so indicates a high viral load. However since mutant versions of Hepatitis B do not always produce the "e" antigen this test can be used to determine viral load in those cases.