The aim of this study was to assess the incidence of decompensation (ascites, jaundice, variceal bleeding, and encephalopathy), hepatocellular carcinoma (HCC) and death or liver transplantation in patients with compensated hepatitis C virus (HCV)-related cirrhosis, taking into account the viral genotype and interferon (IFN) therapy. Between 1989 and 1994, 668 patients with no clinical evidence of decompensation were referred to our department for liver biopsy because of positivity for anti-HCV antibodies and elevated aminotransferase activity; 103 of these patients had cirrhosis. The median follow-up was 40 months. Fifty-nine patients were treated with IFN for a mean duration of 11+/-6 months; 3 (5%) had a prolonged biochemical and virological response. Baseline characteristics of IFN-treated and untreated patients were not significantly different. HCV genotypes (InnoLiPa) were predominantly 1b (48%) and 3a (20%). During follow-up, complications of cirrhosis occurred in 26 patients, HCC in 11 patients, and decompensation not related to HCC in 19 patients. Sixteen patients died, 94% of liver disease. Three patients were transplanted for liver failure. The 4-year risk of HCC was 11.5% (annual incidence 3.3%) and that of decompensation was 20%. Survival probability was 96% and 84% at 2 and 4 years, respectively. In multivariate analysis, the absence of IFN therapy was the only independent factor predictive both for HCC and decompensation. A low albumin level at entry and the absence of IFN therapy were the two independent factors predictive of death or liver transplantation. Probability of survival at 2 and 4 years was significantly different between IFN-treated and untreated patients (respectively 97% and 92% vs 95% and 63%, P < .0001). In conclusion, in patients with compensated HCV-related cirrhosis: 1) complications of cirrhosis are frequent, whatever the viral genotype; and 2) the severity of cirrhosis and the absence of IFN therapy are independently predictive of bad outcome.