Primary biliary cirrhosis: family stories

Abstract

Primary biliary cirrhosis (PBC) is a chronic immune-mediated cholestatic liver disease of unknown aetiology which affects mostly women in middle age. Familial PBC is when PBC affects more than one member of the same family, and data suggest that first-degree relatives of PBC patients have an increased risk of developing the disease. Most often, these familial clusters involve mother-daughter pairs, which is consistent with the female preponderance of the disease. These clusters provide evidence towards a genetic basis underlying PBC. However, clusters of nonrelated individuals have also been reported, giving strength to an environmental component. Twin studies have demonstrated a high concordance for PBC in monozygotic twins and a low concordance among dizygotic twins. In conclusion, studies of PBC in families clearly demonstrate that genetic, epigenetic, and environmental factors play a role in the development of the disease.

Figure 1

Understanding the pathogenesis of the disease also stems from studies of familial primary biliary cirrhosis (PBC). Clues as to the pathogenesis of the disease are provided by population studies involving a large number of families of affected individuals and case reports (see also Table 1). These studies support the notion that the pathogenesis of the disease is complex, and that genes, epigenetic factors, and environment are mostly likely involved in concert rather than in isolation. The relative contribution of each of those factors is largely unknown and may vary among individuals and clusters. Their participation may be important for the induction of the immunopathological processes leading to PBC development, but may also be important for the progression of the disease towards a favourable slow pace or an unwanted progressive deterioration.