Effect of antiviral treatment on evolution of liver steatosis in patients with chronic hepatitis C: indirect evidence of a role of hepatitis C virus genotype 3 in steatosis

Abstract

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.

Steatosis and progression of fibrosis in untreated patients with chronic hepatitis C infection†

“…This possibility would also explain why steatosis is often associated with fibrosis in cross-sectional studies and might correlate with progression of fibrosis in longitudinal studies when initial disease severity was not controlled for adequately. [16][17][18][19][20]29 Thus, these findings might indicate that steatosis is the result rather than the cause of disease severity and disease progression.…”

Chronic hepatitis C: pathological anatomy

“…In a series of patients with genotype 3 and steatosis, a sustained virological response led to regression of steatosis in 91% of the cases, a much higher index than the 19% observed for those who did not present sustained virological response [6], making the cytopathic effect a more consistent cause of steatosis. Other authors have reported similar results [22,36].…”

“…The evaluation of the presence of steatosis, its scoring, and the evaluation of the presence of associated steatohepatitis has gradually become more important [6,7,12,16,19,20,24,[29][30][31][32]36,40].…”

Evolving Trends in the Hepatitis C Virus Molecular Epidemiology Studies: From the Viral Sequences to the Human Genome

“…Several reports have demonstrated a statistically significant relationship between HCV genotype 3, the injecting drug abuse, and a younger age of infection [45][46][47][48][49]. Moreover, by comparing patients infected with genotype 3 and those infected with other genotypes, numerous groups have revealed an association between this genotype and hepatic steatosis [50][51][52][53][54][55], and a severe histopathological manifestation of CHC which can improve after achieving SVR with the antiviral treatment [56][57][58].…”