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The role of hepatitis B virus (HBV) and hepatitis C virus (HCV) as a major cause of chronic liver disease is now accepted worldwide. This study was aimed at evaluating the natural history of the disease in patients with virus-induced chronic active hepatitis or cirrhosis, and the influence played by age, sex and etiology, liver function tests and by the occurrence of different complications. We retrospectively examined the clinical records of 506 inpatients: 194 were affected by chronic active hepatitis (125 males, 69 females, mean age 45 +/- 11 years, 146 HCV- and 48 HBV-related), and 312 by cirrhosis without clinical evidence of portal hypertension (178 males, 134 females, mean age 53 +/- 9 years, 249 HCV- and 63 HBV-related). The occurrence of cirrhosis in the chronic active hepatitis group was then calculated, together with the occurrence of complications and the cumulative mortality rate of established cirrhosis. During follow-up 93 patients with chronic hepatitis developed cirrhosis. The cumulative probability of developing cirrhosis in this group was 6.64% at 5 years, 56.1% at 10 years and 86.8% at 15 years. These patients were therefore included in the cirrhosis group for the final analysis, so that a total of 405 cirrhotic patients were evaluated: these patients had a cumulative survival rate of 99.1% at 5, 76.8% at 10 and 49.4% at 15 years. Comparing the age-adjusted death rate of our patients with the general Italian population, we observed that in patients with liver cirrhosis it was 3.14 and 2.84 times higher in men and women, respectively. Bilirubin was an independent indicator of survival. Several complications, such as esophageal varices, ascites, jaundice, hemorrhage, hepatic encephalopathy and hepatocellular carcinoma significantly reduced the survival rate and were indicated as major complications, while thrombocytopenia, cholelithiasis and diabetes did not affect survival and thus were called minor complications. Incidence of hepatocellular carcinoma was very high especially in males, without correlation with etiology. In conclusion, the progression of virus-induced chronic active hepatitis to cirrhosis is not influenced by sex and etiology. Similarly, the different etiology does not modify the natural history of cirrhosis while the occurrence of one or more major complications significantly shortens survival. The longer survival rate observed in patients with cirrhosis included in this study is probably due to the selective inclusion of patients with early disease and no evidence of portal hypertension.