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Previous studies have investigated extrahepatic multiple primary malignancy (EHPM) associated with hepatocellular carcinoma (HCC). However, its correlation with viral infection, such as hepatitis B virus (HBV) or hepatitis C virus (HCV), has not been examined. The aim of this study is to investigate the association between EHPM and hepatitis infection in HCC patients. A total of 412 patients who underwent surgical resection for primary HCC were enrolled. Viral infection was evaluated by serum HBV surface antigen (HBs Ag) and HCV antibody (HCV Ab). Sixty-eight (16.5%) patients had one or more EHPM. The most frequent EHPM was gastric cancer ( n  = 32) in this cohort. No statistical significance was observed in the distribution of viral infection and incidence of entire EHPM. However, HCV Ab, HBs Ag, and negative status for both were correlated with the frequency of gastric ( P  = 0.0194), urinary tract ( P  = 0.0067), and breast cancer ( P  = 0.0036), respectively. Infection of  Helicobacter pylori  was investigated by immunohistochemistry in gastric EHPM and resulted that 20 out of 21 analyzed cases were negative for  Helicobacter pylori . Although it should be verified by well-designed large cohort studies, the current results suggested correlation between HCV infection and gastric cancer, HBV infection and urinary tract cancer and viral hepatitis-free status and breast cancer in HCC patients.

Analysis of Extrahepatic Multiple Primary Malignancies in Patients with Hepatocellular Carcinoma according to Viral Infection Status