Familial primary biliary cirrhosis in Hiroshima

Primary biliary cirrhosis (PBC) is an autoimmune Liver disease characterize d by the presence of anti-mitochondrial antibodies and chronic inflammatory destruction of septal and intrahepatic bile ducts. Although there are no o bvious associations of PBC with MHC class I or class II genes, there appear s to be a significant increased risk of developing disease within families. Clearly, a combination of genetic and environmental factors play a role in disease pathogenesis, although the relative contributions of each are uncl ear. In this study, we have taken advantage of the well-defined health-care system in Hiroshima prefecture, where PBC is a reportable disease. In the period 1988-1997, 156 new patients with PBC in a total population of 2,873, 000 were diagnosed. These patients included 18 subjects that were derived f rom eight different families in which more than one family member had a his tory of PBC; this reflects a frequency of 5.1% and further shows that the p revalence of PBC is greatly increased in family members. Of interest, the m edian age of onset of PBC in second generation patients was much younger (3 3.4 +/- 10.8 years) compared to median disease onset in general patients wi th PBC in Hiroshima.(55.6 +/- 12 years). In fact, it was striking that the onset of disease in family members often occurred within a few years of eac h other. We also noted that sera of affected members had similar AMA reacti ve profiles against recombinant PDC-E2 BCKD-E2 and OGDC-E2; the major autoa ntigens of PBC. Similar HLA types were found within affected members of a p edigree but the data is limited because of absence of similar typing of una ffected members. The increased family history of PBC, and the earlier onset of disease in second generation members, suggests that environmental agent s are an important risk factor for the development of disease. We suggest t hat genomic analysis in familial PBC will be important to identify the mech anisms of genetic susceptibility. (C) 1999 Academic Press.