Hepatitis C virus infection as a likely etiology of intrahepatic cholangiocarcinoma

Abstract

Although hepatitis C virus (HCV)-related cirrhosis has been suggested as a risk factor for intrahepatic cholangiocarcinoma (ICC), few sizeable studies have tested this hypothesis. We investigated ICC risk factors, with special reference to HCV infection. We conducted a hospital-based case-control study including 50 ICC patients and 205 other surgical patients without primary liver cancer. HCV seropositivity was detected in 36% of ICC patients and 3% of controls. By univariate analysis, the odds ratio (OR) for association of anti-HCV antibodies with development was 16.87 (95% confidence interval (CI), 5.69 to 50.00). History of blood transfusion or diabetes mellitus, elevated serum total bilirubin, elevated aspartate aminotransferase and alanine aminotransferase, decreased serum albumin and decreased platelet count were identified as other possible ICC risk factors. By multivariate analysis, anti-HCV antibodies (adjusted OR, 6.02; 95% CI, 1.51 to 24.1), elevated alanine aminotransferase, decreased serum albumin, and decreased platelet count were found to be independent risk factors for ICC development. As liver status worsened, the adjusted OR for ICC tended to increase. HCV infection is a likely etiology of ICC in Japan. ntrahepatic cholangiocarcinoma (ICC), a malignant tumor arising from bile duct epithelium, is the second most common primary liver cancer, following hepatocellular carcinoma (HCC). Established risk factors for HCC include chronic active hepatitis, and hepatic fibrosis induced by hepatitis virus infection or heavy alcohol intake. On the other hand, risk factors for ICC remain uncertain. Hepatitis C virus (HCV)-related cirrhosis has been suggested as a risk factor for ICC, 1, 2) but confirmation is required. We therefore investigated risk factors for ICC, with special reference to HCV infection. Patients and MethodsWe conducted a hospital-based study using a matched case-control design, including 50 patients with pathologically diagnosed ICC and 205 other surgical patients without primary liver cancer including ICC.Patients. Fifty patients were treated for ICC between January 1991 and December 2002 in the two major medical centers of Osaka City (Department of Gastroenterological and HepatoBiliary-Pancreatic Surgery, Osaka City University Hospital; Department of Gastrointestinal Surgery, Osaka City General Hospital). ICC was diagnosed by pathologic examination. Two to five control patients at the two medical centers were matched with each ICC patient according to gender, 5-year age group, and operation date (within 1 year). Patients with HCC were excluded from the control group since hepatitis B virus (HBV) infection and HCV infection are established etiologic agents of HCC. In all, control patients numbered 205. This study was conducted in accordance with the Helsinki Declaration and the guidelines of the ethics committees at our institutions.Etiologic factors and data collection. Factors evaluated for association with ICC risk included habits such as alcohol consumption and smoking; family histor...

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