Familial primary biliary cirrhosis reassessed: a geographically-based population study

Background/Aims: Development of primary biliary cirrhosis in the close rela tives of patients with the disease has been reported in several series, sug gesting a genetic component to disease susceptibility. In this study we set out to calculate, as accurately as possible, the prevalence of familial pr imary biliary cirrhosis in a geographically-based population. Using local p opulation prevalence data, we have also calculated the first-degree relativ e, sibling and offspring relative risks of overt primary biliary cirrhosis development. Methods: All patients with definite or probable primary biliary cirrhosis i n the city of Newcastle-upon-Tyne, England, were identified by an exhaustiv e case-finding search and were prospectively interviewed by a single invest igator. Full details of family pedigree and familial primary biliary cirrho sis history were obtained. Results: One hundred and seventy-three patients were identified, with 160 p articipating in the study. Thirteen reported a family history of primary bi liary cirrhosis. In three cases, both relative pairs were within the study group. The prevalence of a positive family history of primary biliary cirrh osis was therefore 10/ 157 (6.4% [95% Confidence Interval 2.6-10.2%]), 8/10 cases occurring in first-degree relatives. The patients had a total of 111 8 first-degree relatives Give or dead) and 468 siblings. The first-degree r elative prevalence of primary biliary cirrhosis was 0.72% [0.2-1.2%] (sibli ngs 0.41% [-0.2-1.0%]). The offspring prevalence was 1.2% [0.04-2.4%], (2.3 % [0.1-4.5%] for daughters). The sibling relative risk (lambda(s)) was 10.5 . Conclusions: The overall prevalence of definite or probable primary biliary cirrhosis in the first-degree relatives of existing patients is <1%. The r isk of disease is not, however, uniform, the highest prevalence being seen in the daughters of patients. Suspicion of disease should therefore be high est in this relative group. The calculated lambda(s) for primary biliary ci rrhosis in this geographically-based study is significantly lower than prev ious estimates from case-note-derived case series, but similar to values se en in other autoimmune diseases.