Increased cancer risk in a large population-based cohort of patients with primary biliary cirrhosis: follow-up for up to 36 years

The natural history of primary biliary cirrhosis (PBC) has so far mainly been studied in tertiary referral centres. The aim of the present investigation was to describe the natural history of PBC in a large population-based cohort in order to identify risk factors for development of malignancies and disease progression. Four independent hospital databases were searched in 44 hospitals in a geographically defined area, after which all medical records were evaluated on site. In addition, PBC registries in the three liver transplant centers were checked for missed referrals from the area of interest. In total, 992 cases fulfilled the inclusion criteria. The median follow-up was 73 months (range 0-434). Mortality was similar to the age- and gender matched population (SMR 1.1; 95 % CI 0.9-1.4). Male gender, smoking, and elevated bilirubin, decreased albumin, and elevated AST at time of diagnosis, were associated with an increased risk for the combined end point PBC-related death or liver transplantation. In total, 133 (13 %) patients developed one or more malignancies (SIR 1.5; 95 % CI 1.1-1.9). There was a ninefold increased risk of developing hepatobiliary malignancies (SIR 9.4; 95 % CI 3.04-21.8), a fivefold increased risk of developing urinary bladder cancer (SIR 5.0; 95 % CI 1.6-11.6), and a 1.8-fold increased risk of developing breast cancer (SIR 1.8; 95 % CI 1.08-2.81). PBC is associated with an increased risk of hepatobiliary, bladder and breast cancer. Still, survival-under treatment with ursodeoxycholic acid (UDCA)-was comparable to the general population in this population-based study.