Clinical course and risk factors of hepatitis C virus related liver disease in the general population: report from the Dionysos study

Background-The severity, clinical course, and risk of hepatitis C virus (HC V) related chronic liver disease are still rather poorly defined. Aims-To investigate the prevalence, risk factors, and severity of HCV relat ed liver disease in the general population, and investigate whether infecti on with a specific genotype is associated with an increased risk of cirrhos is or hepatocellular carcinoma. Methods-HCV RNA determination by polymerase chain reaction (PCR) and HCV ge notyping were performed in all anti-HCV positive subjects belonging to the Dionysos study (6917 subjects). Diagnosis of cirrhosis and hepatocellular c arcinoma was established by liver biopsy in all cases. All the data were an alysed by univariate and multivariate statistics in all the cohort. To inve stigate the natural history of HCV infection, anti-HCV positive subjects we re followed up every six months for three years with liver function tests a nd ultrasonograms. Results-The overall prevalence of HCV RNA positivity was 2.3%. Positivity i ncreased progressively with age, and was higher in women (ratio of men to w omen = 0.7). Genotypes 1b and 2a were the most frequent (42 and 24% of HCV RNA positive patients), with a prevalence of 1 and 0.6% respectively. Intra venous drug use, blood transfusions received before 1990, history of previo us hepatitis among the cohabiting, and history of animal (mainly dogs) bite s were significantly (p<0.05) associated with HCV infection, independently of age and sex. Multivariate analysis showed that, independently of age, se x, and alcohol intake, genotype Ib infection, with or without coinfection w ith other genotypes, is the major risk factor associated with the presence of cirrhosis and/or hepatocellular carcinoma. During the three years of fol low up, 57 (35%) of the HCV RNA positive subjects had consistently normal a lanine aminotransferase and gamma-glutamyltransferase values. Two of the 22 HCV RNA positive cirrhotic patients, all drinking more than 90 g of alcoho l a day, developed hepatocellular carcinoma (incidence rate = 3.0% per year ). Conclusions-In the general population of Northern Italy, HCV infection is w idespread, but only less than 50% of the anti-HCV positive subjects, partic ularly those infected with genotype 1b, are associated with a more severe l iver disease. Alcohol consumption greater that 30 g a day significantly agg ravates the natural course of the disease.