Natural history of chronic hepatitis C.

The natural history of chronic hepatitis C is one of a slow progression from early stage chronic hepatitis without fibrosis to cirrhosis or hepatocellular carcinoma (HCC). The disease progresses to advanced stage chronic hepatitis C over 10-30 years. Data from Japan indicate that mortality associated with chronic hepatitis C results mainly from the development of HCC. We studied 186 patients referred between 1968 and 1994. The mean follow-up interval was 8.6 (2-23) years. HCC developed in 34 patients (18%). The cumulative probability of HCC development was 4% at 5 years, 18% at 10 years and 45% at 15 years. Univariable analysis indicated that age at entry, fibrosis stage, inflammation activity and the status of IFN treatment (treated vs untreated) were predictive risk factors for developing HCC in patients with chronic hepatitis C. Multivariable analysis of these risk factors indicated that age at entry (> 50 vs < 50; Risk Ratio = 3.2, P< 0.005) and fibrosis stage (F3 vs F0; Risk Ratio= 5.6, P< 0.005) are independent risk factors for HCC. From these results it was concluded that (1) 20% of patients referred to liver clinics with chronic hepatitis C in Japan can be expected to develop HCC over a 10 year period; (2) the risk of HCC increases with progression of liver fibrosis (F3, F4) and age (greater than 50 years old) at the time of diagnosis and (3) the degree of liver fibrosis is a critical predictive factor for the occurrence of HCC.