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Background and aim: Recent studies suggest that liver steatosis in chronic hepatitis C may be the expression of a direct cytopathic effect of hepatitis C virus (HCV), particularly in patients infected with genotype 3. To investigate this hypothesis, we studied the relationship between steatosis evolution and HCV clearance after antiviral treatment in patients with chronic hepatitis C and paired liver biopsies. Methods: A total of 151 patients (37 with HCV genotype 3; 114 with HCV non-3 genotypes) were selected according to the following criteria: presence of steatosis at initial biopsy; no antiviral treatment prior to the first biopsy; antiviral treatment received between the two biopsies; body mass index (BMI) ,28 kg/m 2 ; absence of excessive alcohol intake; no serum hepatitis B surface antigen or human immunodeficiency virus antibodies; and absence of diabetes mellitus. Evolution of steatosis was examined by comparing steatosis grades between the two biopsies. Results: Twenty five patients (16.5%) were sustained virological responders (SVR) to antiviral treatment. Steatosis evolution after antiviral treatment was as follows: improvement in 36% of cases; stability in 51%; and worsening in 13%. Steatosis improvement was significantly more frequent in SVR than in nonresponders (NR) (64% v 31%; p,0.004). This significant difference occurred in patients infected with genotype 3 (91% v 19%; p,0.0001) but not in those infected with non-3 genotypes (43% v 34%; NS). Among the 25 SVR, improvement in steatosis was significantly more frequent in patients infected with genotype 3 than in those infected with non-3 genotypes (91% v 43%; p,0.04) whereas in NR, improvement in steatosis did not differ between those infected with genotype 3 and non-3 genotypes (19% v 34%; NS). In multivariate analysis, four factors were independently associated with steatosis improvement: sustained virological response to antiviral therapy (odds ratio (OR) 6.06 (95% confidence interval (CI) 1.61-22.9); p = 0.01), severe steatosis (OR 5.50 (95% CI 1.54-19.6); p = 0.01), HCV genotype 3 (OR 2.90 (95% CI 0.85-10.0); p = 0.07), and BMI .25 kg/m 2 (OR 0.24 (95% CI 0.08-0.73); p = 0.02). Conclusions: Our results showed significant improvement in steatosis in patients infected with HCV genotype 3, who achieved sustained viral clearance. This provides further evidence for direct involvement of HCV genotype 3 in the pathogenesis of hepatic steatosis.

The aim of this study was to determine a cost-effective strategy for the diagnosis of hepatitis C virus ( The diagnosis of hepatitis C virus (HCV) infection is based on the detection of anti-HCV antibodies in serum, generally by means of enzyme-linked immunosorbent assays (ELISA). Two different settings must be considered: 1) Blood banks routinely perform anti-HCV testing in blood donors to identify potentially infectious donations and to avoid posttransfusion HCV infection; 2) clinical laboratories routinely search for anti-HCV antibodies in patients with risk factors for parenterally acquired viral infections or clinical symptoms compatible with HCV infection to make appropriate clinical decisions, including therapeutic ones. By analogy with human immunodeficiency virus diagnosis, the French laws have been obliging to perform two different ELISA tests in the routine diagnosis of HCV infection in clinical laboratories for several years, while only one test was needed for blood screening.First-generation anti-HCV ELISAs were lacking sensitivity as well as specificity. This is why first-generation confirmatory assays based on immunoblot testing were developed and systematically used in samples positive in ELISA. 1,2 Since then, ELISA assays have considerably improved, and the second-or third-generation tests available today are both highly sensitive and specific. 3-6 Nevertheless, second-or third-generation immunoblot tests are still used for confirmation in most laboratories. 7,8 The detection of HCV antibodies in serum does not provide information on the replicative status of HCV, a parameter that can be useful in the management of infected patients. Polymerase chain reaction (PCR)-based assays have been developed and are capable of detecting minute amounts of HCV RNA in serum or plasma.The aim of this work was to determine whether a double ELISA determination and confirmation of positive ELISA results with immunoblot assays are still useful in clinical laboratories performing routine diagnosis of HCV infection. MATERIALS AND METHODSFrom January 1 to May 22, 1996, 3,014 consecutive requests for the detection of anti-HCV antibodies were sent to the virology laboratory by the various medical departments of our institution.The serum samples were routinely tested for the presence of anti-HCV antibodies with two different ELISAs: ORTHO HCV 3.0 ELISA Test System (ELISA3.0 HCV; Ortho Clinical Systems, Raritan, NJ), and MONOLISA anti-HCV New Ag (MONOLISA HCV; Sanofi Diagnostics Pasteur, Marnes-la-Coquette, France). ELISA 3.0 detects antibodies directed to core, nonstructural (NS) 3, NS4, and NS5 HCV antigens, while MONOLISA HCV detects antibodies directed to core, NS3, and NS4 antigens. 9 Different peptides are used in the two assays. 9 The assays were perfomed according to the manufacturers' instructions, and, in each sample, the optical density (OD) ratio was calculated by dividing the sample OD by the assay control OD. Samples with an OD ratio Ն2 were considered positive, samples with an OD ratio between 1 and 2 we...

SUMMARYAim: To evaluate the effects of minimal to moderate alcohol consumption on the severity of histological lesions in patients with chronic hepatitis C. Methods: Daily alcohol intake (none, 1-20, 21-30, 31-50 g/day) and histological activity and fibrosis were recorded in 260 patients with chronic hepatitis C. Results: The proportion of patients with moderate (A2) or marked (A3) activity increased gradually from 53.8% in abstinent patients to 86.5% for an intake between 31 and 50 g/day (P ¼ 0.003). In multivariate analysis, age > 40 years, alcohol intake between 31 and 50 g/day and moderate or severe steatosis were independently related to histological activity. The proportion of patients with moderate (F2) or marked (F3) fibrosis or cirrhosis (F4) gradually increased from 29.0% in abstinent patients to 67.6% for an intake between 31 and 50 g/day (P < 0.001). Multivariate analysis also showed that alcohol intake between 31 and 50 g/day, moderate or severe steatosis and histological activity were independently related to fibrosis. The deleterious effect of alcohol intake on histological lesions differed according to gender. Conclusions: This study demonstrates that both activity and fibrosis gradually increase according to the amount of alcohol ingested, and that even moderate alcohol consumption, as low as 31-50 g/day in men and 21-50 g/day in women, may aggravate histological lesions in patients with chronic hepatitis C.