Hepatic and extrahepatic malignancies in primary biliary cirrhosis

Hepatocellular carcinoma (HCC) is rarely reported as a complication of primary biliary cirrhosis (PBC). However, data suggest that patients with PBC have an increased incidence of breast cancer when compared with the general population. Our aim was to analyze the incidence of malignancies in a large series of PBC patients from North-East Italy; to compare findings with those obtained in the general population of the same geographical area, as derived from the general cancer registry; and to study any possible adjunctive risk factor for malignancy. The overall sample included 175 patients (9 males, 166 females). The mean age at presentation was 50.8 years (range 23-77); 17 patients had histological stage I, 45 had stage II, 76 had stage III, and 37 had stage IV. The prevalence of gynecological diseases obtained from the past history of the females included 19.9% miscarriages, 12% hysterectomies, and 2.4% curettages. The follow-up period was 1,187 person/years (average 6.8 yrs per person as a mean). The comparison of the incidence of malignancies between the study group and the general population was obtained by the proportional incidence ratio (PIR), which is the ratio between the cases observed and the expected number of cases in the study group. Logistic regression analysis was performed utilizing the risk factors significantly associated with cancer development in the univariate analysis. Extrahepatic malignancies developed in eight cases (4.5%) and HCC in a further four cases (2.3%), all associated with cirrhosis. Two of the four patients with HCC had a superinfection with hepatitis C virus (HCV). Breast cancer developed only in two patients. The PIR for HCC was 26.27 (95% CI 6.8-46.5), whereas the PIR for breast cancer was 0.43. The logistic regression analysis indicated that a history of cigarette smoking and HCV-RNA positivity were independent variables for the development of HCC. HCC has a relatively high prevalence in PBC and HCV superinfection may play an important part in favoring HCC. The incidence of breast cancer is not significantly higher in PBC than in the general population of the same area.