Hepatitis B Virus Infection and Risk of Intrahepatic Cholangiocarcinoma and Non-Hodgkin Lymphoma: A Cohort Study of Parous Women in Taiwan

Few studies have evaluated the risk of cancers other than hepatocellular carcinoma associated with hepatitis B virus (HBV) infection. This study aimed to estimate incidence rates of intrahepatic cholangiocarcinoma (ICC) and non-Hodgkin lymphoma (NHL) and its major subtypes in a nationwide cohort of parous women and to assess their associations with chronic HBV infection. We conducted a cohort study including 1,782,401 pregnant Taiwanese women whose HBV serostatus was obtained from the National Hepatitis B Vaccination Registry. Newly diagnosed ICCs and NHLs were ascertained through data linkage with the National Cancer Registry. Risks of ICC and NHL were assessed using Cox proportional hazards regression models. After a mean of 6.91 years of follow-up, there were 18 cases of ICC and 192 cases of NHL, including 99 cases of diffuse large B-cell lymphoma (DLBCL). Incidence rates of ICC were 0.09 and 0.43 per 100,000 person-years, respectively, among women who were hepatitis B surface antigen (HBsAg)-seronegative and HBsAg-seropositive, showing an age-adjusted hazard ratio (HRadj) (95% confidence interval [CI]) of 4.80 (1.88-12.20). The incidence rates of NHL overall for HBsAg-seronegative and HBsAg-seropositive women were 1.23 and 3.18 per 100,000 person-years, respectively, with an HRadj (95% CI) of 2.63 (1.95-3.54). Among NHL subtypes, HBsAg-seropositive women had an increased risk of DLBCL compared with those who were HBsAg-seronegative (incidence rates: 1.81 and 0.60 per 100,000 person-years, respectively; HRadj [95% CI]: 3.09 [2.06-4.64]). The significantly increased risk was not observed for other specific subtypes of NHL. Conclusions: Chronic HBV infection was associated with an increased risk of ICC and DLBCL in women. Our data suggested a possible etiological role of HBV in the development of ICC and specific subtypes of NHL. (HEPATOLOGY 2011;53:1217-1225)