BACKGROUND/AIMS: Flare-up of hepatitis due to the reactivation of hepatitis B virus (HBV) is a well-known complication in patients with malignant disease who receive chemotherapy. Despite the widespread use of chemotherapy for patients with HBV-related hepatocellular carcinoma (HCC), there is little corresponding data on exacerbation of liver damage in these patients. In the present study, we investigated the associating factors in exacerbation of liver damage in patients with HBV-related HCC who were undergoing trans-hepatic arterial infusion chemotherapy (THAIC). PATIENTS AND METHODS: Thirty-three patients who received THAIC for HCC were investigated. All patients were hepatitis B surface antigen positive. Hepatitis e antigen and antibody were generally tested at baseline and within 1 month of final chemotherapy. Serum alanine aminotransferase, asparate aminotransferase, albumin, total bilirubin, and prothrombin time were estimated once a week or every 2 weeks. HBV-DNA levels were measured at baseline and once a month. Mutation in the regions of precore and core promoter in HBV DNA was generally estimated at baseline and within 1 month of final chemotherapy. RESULTS: Eight patients with hepatitis Be antigen positive and hepatitis Be antibody negative at baseline were found to have exacerbation of liver damage during or after chemotherapy. Of these, three patients died of progressive liver failure. There was no association between exacerbation of liver damage and age, sex, hepatic reserve function, HBV-DNA levels, precore and core promoter sequencing, therapeutic regimen, or tumor stage. The only associating factor was HBeAg positivity. CONCLUSIONS: These results suggest that hepatitis B e antigen positivity is a significant associating factor in exacerbation of liver damage during or after chemotherapy in patients with HBV-related HCC.