Elsevier

Journal of Hepatology

Volume 33, Issue 1, July 2000, Pages 106-115
Journal of Hepatology

Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3

https://doi.org/10.1016/S0168-8278(00)80166-XGet rights and content

Abstract

Background/Aims: Patients infected with the hepatitis C virus (HCV) often have liver steatosis, suggesting the possibility of a viral cytopathic effect. The aim of this study was to correlate the occurrence and severity of liver steatosis with HCV RNA type, level and sequence of the core-encoding region.

Methods: We scored the liver steatosis in 101 HCV-infected individuals carefully selected to exclude other risk factors of a fatty liver. Results were compared with HCV RNA genotype and level in serum and liver. In selected patients, we assessed the effect of antiviral therapy on steatosis and the relationship between nucleocapsid sequence heterogeneity and fat infiltration.

Results: Steatosis was found in 41 (40.6%) patients, irrespective of sex, age or route of infection. HCV genotype 3 was associated with higher steatosis scores than other genotypes. A significant correlation between steatosis score and titer of intrahepatic HCV RNA was found in patients infected with genotype 3, but not in those infected with genotype 1. In selected patients, response to alpha-interferon was associated with the disappearance of steatosis. Analysis of the nucleocapsid of 14 HCV isolates failed to identify a sequence specifically associated with the development of steatosis.

Conclusions: We provide virological and clinical evidence that the steatosis of the liver is the morphological expression of a viral cytopathic effect in patients infected with HCV genotype 3. At variance with published evidence from experimental models, the HCV nucleocapsid protein does not seem to fully explain the lipid accumulation in these patients.

Section snippets

Patient populations

A total of 101 patients were studied. A first group consisted of 70 immunocompetent patients with persistent HCV infection, as documented by the presence of HCV RNA in serum detected by a 2nd generation qualitative RT-PCR assay (Amplicor™, Roche, Switzerland; sensitivity limit 100 copies/ml) for at least 6 months, and histologically-proven chronic hepatitis. There were 38 males and 32 females. The median age was 44.1 years (range 19–67). All patients lacked factors likely to be associated with

Immunocompetent chronic hepatitis C patients: virological correlations

Among the 70 immunocompetent chronic hepatitis C patients, 28 (40%) had liver steatosis with scores of 1 (18 cases), 2 (4 cases) or 3 (6 cases). Patients with or without steatosis had similar male to female ratio, mean age and route of infection (Table 1). HGV RNA was tested in 40 patients and found in the serum of 2/18 patients with steatosis and of 2/22 patients without steatosis (p=0.75) (Table 1). Steatotic patients were less likely than non-steatotic patients to be infected with HCV

Discussion

We have shown that the liver steatosis score is significantly higher in chronic hepatitis C patients infected with HCV genotype 3 than in case of infection with other viral genotypes, and that the highest levels of correlation between steatosis score and intrahepatic HCV RNA titer are reached when only patients infected with HCV genotype 3 (but not patients with genotype 1) are considered. Similarly, the occurrence of severe steatosis of the liver after OLT is associated with infection with HCV

Acknowledgements

This work was partially supported by contracts nos. 32-42556-94 (to A.H.) and 3200-052193.97/1 (to F.N.) from the Swiss National Science Foundation, a grant from the Fondation Cancer-Solidaritè, Genève (to K.A.) and a Schering-Plough unrestricted educational grant. The authors thank Lelio Orci, Ferruccio Bonino and Jean-Michel Pawlotsky for advice and criticism and Joachim Brault, Colette Rossier and Marilyne Baud for their skilled technical help.

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