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Background. Patients with cirrhosis have a high risk of hepatocellular carcinoma (HCC) but it is unclear how the etiology of liver disease influences tumor development. The authors evaluated hepatitis B and C virus (HBV, HCV) infection in cirrhosis in relation to the risk of HCC. Methods. Two hundred and ninety consecutive cirrhotic patients were followed prospectively with periodic ultrasound examination. At entry, patients were tested for markers of HBV and HCV to assess relation to tumor development during follow‐up. Results. Twenty and five‐tenths percent of patients were hepatitis B surface antigen (HBsAg) positive and 68.9% were positive for HCV antibodies. Previous alcohol abuse was present in 26.2%. During follow‐up (46.3 ± 21.4 months), HCC developed in 32 patients (11.0%) (annual incidence approximately 3%) including 19.6% of HBsAg‐positive patients, 12.2% of HCV antibody positive patients and 14.4% of patients with a history of alcohol abuse. The highest rate of HCC was in patients with dual HBsAg and anti‐HCV positivity with or without previous alcohol abuse, whereas the lowest incidence (0%) was in cases without risk factors. By univariate analysis, age older than 59 years (P < 0.005), longer duration of cirrhosis (P < 0.005), serum alpha‐fetoprotein levels higher than 20 ng/ml (P < 0.05), and dual HBsAg and HCV positivity (P < 0.02) appeared to be associated with HCC. By multivariate analysis, age (P < 0.01), positivity for HBsAg and HCV antibodies (P < 0.05), male sex (P < 0.05), and previous alcohol abuse (P < 0.08) were independently related to tumor appearance. Conclusions. These results, although confirming that male sex and previous alcohol abuse are risk factors for hepatocellular carcinoma in cirrhosis, indicate that concurrent hepatitis B and C virus infection determines the highest risk of developing hepatocellular carcinoma.

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