Hepatitis Central

Hepatology, December 1999, p. 1530-1531, Vol. 30, No. 6

Correspondence
Body Composition and Hepatic Steatosis as Precursors of Fibrosis in Chronic Hepatitis C Patients

To the Editor:

The article by Hourigan et al.¹ suggests that an increase in the body mass index (BMI) is related to steatosis in chronichepatitis C (CHC) and that steatosis may contribute to fibrosis.The observations are interesting, but we are concerned that factorsother than BMI, specifically viral genotype, need to be considered.Recently, we and others^2-4 reported that steatosis was more highlyassociated with genotype 3 than with other hepatitis C virus (HCV)genotypes. Indeed, Hourigan et al. found a higher grade of steatosisin patients with viral genotype 3, although this did not reachstatistical significance because of the small number of patientsfor whom genotyping was done. In addition, it has been demonstratedthat HCV may directly cause steatosis.^5,6

In a cohort of 158 patients with biopsy-proven CHC we have evaluated the correlation between the HCV genotype and a fattyliver. To avoid confounding factors, we excluded patients withdiabetes, dyslipidemia, alcohol intake greater than 30 g/d, geneticor autoimmune hepatic diseases, or hepatitis B virus or humanimmunodeficiency virus infection. None of the patients had receivedprevious treatment with interferon or immunosuppressive agents.HCV genotyping was performed by the INNO LiPA HCV assay (Innogenetics,Zwijnaarde, Belgium). The results (table 1) show that steatosisis more frequent in patients with genotype 3a than with othergenotypes. Patients infected with type 2a/c also show a higherprevalence of steatosis than those infected with genotype 1. Thedifferent prevalence of steatosis among HCV genotypes was independentof BMI, age, sex, levels of viremia, and hepatic iron deposition.On the whole, using the linear regression analysis, we found asignificant association between the grade of steatosis and fibrosis(P < .04) and only a trend in the association between steatosisand BMI (r = .18; P = .07). However, when the data were analyzedby single genotype, there was a direct relationship between thegrade of steatosis and BMI in genotype 1 infection (r = .50; P < .001) but no correlation in genotype 2a/c and 3a infection.

To View This table

table 1.   Prevalence of Steatosis and BMI of 158 CHC Patients According to HCV Genotype

Our study suggests that steatosis in patients with genotypes 3a and 2a/c is related in part to HCV, whereas in genotype 1 infection it is more strictly associated with BMI. Recently, itwas reported that the grade of steatosis in genotype 3a infectionis correlated with the level of intrahepatic HCV replication.⁴We conclude that both host (BMI, diet, diabetes, hyperinsulinemia,alcohol) and viral factors (HCV genotype), alone or in combination,play a role in the development of steatosis in CHC patients. Prognosticand therapeutic implications may differ according to the factor(s)involved.

Luigi Elio Adinolfi, M.D. Riccardo Utili, M.D. Giuseppe Ruggiero, M.D. Institute of Medical Therapy Division of Internal Medicine and Hepatology Second University of Naples Naples, Italy

REFERENCES

1.	Hourigan LF, Macdonald GA, Purdie D, Whitehall VH, Shorthouse C, Clouston A, Powell E. Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis. HEPATOLOGY 1999;29:1215-1219
2.	Adinolfi LE, Utili R, Andreana A, Tripodi M-F, Mormone G, Rosario P, Tonziello A, et al. Hepatitis C virus genotype and levels of viremia: correlation with histological alterations of chronic hepatitis C (CHC) patients [Abstract]. J Hepatol 1999;30(Suppl):136A.
3.	Mihm S, Fayazi A, Hartmann H, Ramadori G. Analysis of histopathological manifestations of chronic hepatitis C infection with respect to virus genotype. HEPATOLOGY 1997;25:735-739
4.	Rubbia-Brandt L, Giostra E, Quadri R, Malè P-J, Mentha G, Spahr L, Zarski J-P, et al. Evidence that liver steatosis is virally-mediated in a subset of patients infected by hepatitis C virus genotype 3 [Abstract]. J Hepatol 1999;30(Suppl):133A
5.	Moriya K, Yotsuyanagi H, Shintani Y, Fujie H, Ishibashi K, Matsuura Y, Miyamura T, et al. Hepatitis C virus core protein induces hepatic steatosis in transgenic mice. J Gen Virol 1997;78:1527-1531
6.	Moriya K, Fujie H, Shintani Y, Yotsuyanagi H, Tsutsumi T, Ishibashi K, Matsuura Y, et al. The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat Med 1998;4:1065-1067 Reply: We agree with Dr. Adinolfi et al. that both host and viral factors play a role in the development of steatosis in patientswith chronic hepatitis C. Since publication of our article,1we have obtained further genotyping results, providing us withthe opportunity to study the association between viral genotypeand steatosis and the relationship between BMI and steatosis separatelyin patients with genotype 1 or3. Viral genotyping was performed in 61 patients with untreated chronic hepatitis C using the Inno-Lipa HCV II assay (Innogenetics,Zwijnaarde, Belgium). Steatosis was graded as previously reported.1The association between viral genotype and steatosis was testedusing the Pearson's 2 statistic and the mean differences in BMI across levels of steatosiswere assessed using one-way analysis ofvariance. There was a striking association between grade of steatosis and viral genotype 3a (table 2) (P = .01). In subjects with viralgenotype 1, there was a significant relationship between increasingBMI and grade of steatosis (P = .03). In the group with viralgenotype 3a, patients without steatosis were leaner (mean BMI24 ± 3.3) than those with steatosis (BMI 27 ± 4.9). However ingenotype 3a, there was no significant relationship between gradeof steatosis and increasing BMI. As previously reported,1 therewas overall a significant association between grade of steatosisand increasing fibrosis, and this did not differ between genotypes1 and 3a. To View This table table 2.   Characteristics and Laboratory Features of Patients Within Each Grade of Steatosis

We agree with the conclusions of Dr. Adinolfi et al. that in patients infected with HCV genotype 1, increasing BMI has a rolein the pathogenesis of steatosis. In patients with genotype 3a,steatosis may be caused by a cytopathic effect of the virus; however,we suspect that host body fat also contributes as a cofactor.This suggests that efforts to restore a lean BMI may be relevantin patients infected with eithergenotype.

Luke F. Hourigan, FRACP⁵
David Purdie, Ph.D.²
Andrew Clouston, FRCPA³
Graeme A. Macdonald, FRACP^4,6
Elizabeth E. Powell, FRACP, Ph.D.>⁵
Departments of ¹Surgery, ⁴Medicine, and ²Social and Preventive Medicine
The University of Queensland
Departments of ³Pathology and ⁵Gastroenterology and Hepatology The Princess Alexandra Hospital
⁶Clinical Sciences Unit
Queensland Institute of Medical Research
Brisbane, Australia

REFERENCES

1. Hourigan LF, Macdonald GA, Purdie D, Whitehall VH, Shorthouse C, Clouston A, Powell EE. Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis. HEPATOLOGY 1999;29:1215-1219

Copyright © 1999 by the American Association for the Study of Liver Diseases.