Development of HCC in patients receiving adefovir dipivoxil for lamivudine‐resistant hepatitis B virus mutants

AIM: To identify factors for the development of hepatocellular carcinoma (HCC) in the patients who receive adefovir add-on lamivudine for treatment of lamivudine-resistant hepatitis B virus (HBV) mutants. METHODS: A total of 247 patients who developed lamivudine-resistant HBV mutants, with an increase of HBV DNA >/= 1 log copies/mL, received adefovir dipivoxil 10 mg add-on lamivudine 100 mg daily during a median of 115 weeks (range: 25-282 weeks). They were followed for the development of HCC by imaging modalities every 3-6 months. RESULTS: HCC developed in 18 of the 247 (7.3%) patients. Eight factors were in significant association with the development of HCC by the univariate analysis. They included age, cirrhosis, platelet counts, levels of bilirubin, aspartate aminotransferase (AST), alanine aminotransferase and alpha-fetoprotein, as well as YMDD mutants at the start of adefovir dipivoxil. By the multivariate analysis, AST levels, YIDD mutants, cirrhosis and age were independent factors for the development of HCC. By the Kaplan-Meier analysis, AST levels >/= 70 IU/L, YIDD mutants, cirrhosis and age >/= 50 years increased the risk of HCC (P = 0.018, P = 0.035, P = 0.002 and P = 0.014, respectively). HCC developed more frequently in the patients with than without cirrhosis at the start of adefovir (10/59 [16.9%] vs. 8/188 [4.3%], P = 0.002). CONCLUSION: HCC can develop in cirrhotic patients receiving adefovir add-on lamivudine. Hence, the patients with baseline AST >/= 70 IU/L and YIDD mutants would need to be monitored closely for HCC.