Highlights of primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is an autoimmune chronic cholestatic liver disease, histopathologically charac­ terized by portal inflammation and immune­mediated destruction of the intrahepatic bile ducts within the portal tracts and epithelioid granulomas around damaged bile ducts. The loss of bile ducts leads to decreased bile secretion and the retention of toxic substances within the liver, resulting in further hepatic damage, fibrosis, cirrhosis and, eventually, liver failure [1]. Serologically, PBC is characterized by the presence of antimito­ chondrial antibodies (AMAs) ­which are present in 90 to 95% of patients and are often detectable years before clinical signs appear [2]; high plasma levels of immuno­ globulin M (IgM) [3]; and high­titer antibodies against nuclear antigens (ANAs). It is estimated that 30 to 50% of patients also have specific ANAs, including antibodies to nucleoporin p62 (Nup62), a glycoprotein located within the nuclear pore complex (NPC) [4]. These antibodies are associated with more severe forms of the disease. While AMA presence is often used for diagnostic purposes, ANAs and Nup62 could be linked to prognosis and are helpful tools in the management of patients with PBC, particularly in the AMA­negative subgroup [5,6]. PBC primarily affects middle­aged women, with a female/male ratio of 9/1, a characteristic shared by other autoimmune diseases [7]. It also seems to be more common among the first­degree relatives of patients [8,9]. Studies of the annual incidence and prevalence of PBC in different geographical areas suggest the impact of ethnic influences, environmental factors and the non­ uniform criteria used for the diagnosis of PBC. PBC still appears to be more frequent in northern Europe and the United States, but overall the incidence ranges between 0.7 and 49 per million population, while the prevalence is between 6.7 and 402 cases per million population [10], thus making PBC a rare disease according to the 2002 Rare Disease Act. Several studies have reported a sub­ stantial increase in PBC prevalence and incidence over recent decades, similar to other autoimmune diseases [11]. This is mostly due to a better and earlier recognition of disease, and to more sensitive diagnostic procedures [12]. PBC is now diagnosed at an earlier stage in its clinical course than it was in the past, with 50 to 60% of patients asymptomatic at diagnosis, and one­third of them remaining symptom free for many years. The diagnosis of PBC is currently based on three criteria: serological positivity for AMA, a cholestatic biochemical picture with elevated levels of serum alkaline phosphatase and γ glutamyl transferase lasting for over 6 months, and histological features compatible with the presence of the disease. A probable diagnosis requires the presence of two of these three criteria, and a definite Abstract