Abstract:The risk of Hepatocellular carcinoma (HCC) is high in HCV-infected patients who have biochemically and histologically active chronic hepatitis. To observe the long prognosis of Chronic Hepatitis C (CHC) patients with stage 3 fi brosis (F3), 55 CHC patients after initial Interferon (IFN) therapy were followed up for up to 12 years (average 9.8 ± 2.3 years). According to the annual average alanine aminotransferase (ALT) levels, patients were grouped into, low (ALT Ϲ 30 IU/l); moderate (ALT Ͼ30 Ͻ80 IU/l) and high (ALT м 80 IU/l) ALT groups. Eleven patients were re-treated with IFN. During the follow-up period of 12 years, HCC developed in 26 patients with an average annual incidence of 3.9%. Biochemical responders to initial IFN therapy (n = 8) and those re-treated with IFN (n = 10), except 1, did not develop HCC. Cox regression analysis to evaluate risk factors for HCC occurrence, found development of Liver Cirrhosis within 3 years of initial IFN therapy(P = 0.05) and the 3 year annual average ALT post initial IFN therapy (P = 0.033) to be signifi cant. The 12 year annual average ALT was also found to be signifi cantly related to HCC occurrence (P = 0.016), on univariate analysis. Patients belonging to the continuously low ALT group (ALT Ϲ 30 IU/l for м3 years), did not develop HCC or receive IFN re-treatment. In CHC patients with F3, after initial IFN therapy, keeping ALT continuously low, below 30 IU/l for 3 years or more seems important. Continuing treatment with anti-infl ammatory drugs along with subsequent IFN re-treatment may prevent or delay HCC even in elderly patients.