Hepatitis C virus infection. Viral genotypes and factors promoting liver fibrosis

Abstract

Hepatitis C virus (HCV) is associated with chronic infection in a majority of infected individuals. Chronic hepatitis C may result in liver cirrhosis or hepatocellular cancer and is therefore considered a major health problem worldwide. In order to determine the relative prevalence of HCV genotypes in our catchment area, sera from 312 patients were analysed. Genotypes 1a (35%) and 3 (31%) were the most common types, followed by genotypes 2 (17%) and 1b (6%). The relative prevalence of genotype 1b decreased in favour of genotype 3 over time. The genotype distribution pattern was different compared with many other regions, which may be explained by relatively recent introduction of HCV to the Swedish population. Histological examination of liver biopsies is essential in the management of patients with chronic hepatitis. Several scoring systems have been proposed, aiming to facilitate interpretation of histological features, one of them by Ishak et al. To evaluate its interobserver reliability and criterion validity, 95 liver biopsies were independently examined by three observers. We found that if a deviance of one categorical level in any variable was not considered relevant, the method was highly reliable. The scale provided an acceptable compromise between complexity and reliability. Accordingly, it was used in the following studies. The progression of fibrosis over time was retrospectively investigated in 98 patients who underwent two liver biopsies before any treatment. Several host and virus-related factors may influence the fibrosis progression and we chose to study the effect of moderate alcohol intake and of fatty infiltration (steatosis) in the liver. Seventy-eight patients with moderate alcohol consumption responded to a self-administered questionnaire for evaluation of "lifetime drinking history". A subgroup of patients with progressive fibrosis had a higher alcohol intake, and higher "drinking frequency", during the period between the biopsies. Multivariate analysis showed that drinking frequency and time between the biopsies were independently associated with fibrosis progression. Thus, moderate alcohol intake seems to influence the fibrosis development. Analysis of the drinking pattern revealed that drinking frequency affects fibrosis more than the quantity consumed on each occasion. The 98 patients with two liver biopsies were examined for the effect of liver steatosis on fibrosis progression. Both prevalence and grade of steatosis were associated with HCV genotype 3, independent of sex, age, body mass index and alcohol use. Progressive fibrosis was more prevalent in patients with steatosis. This effect was mainly seen in genotype 3-infected patients. Our study thus confirms the hypothesis that steatosis is associated with HCV genotype 3, and, furthermore, with progressive fibrosis over time, especially in genotype 3 patients. These data imply that genotype 3-infected patients with steatosis ought to be selected for early antiviral therapy.