The natural history of asymptomatic primary biliary cirrhosis

Abstract

Appreciation of the spectrum of clinical features of primary biliary cirrhosis (PBC) has evolved considerably over the past few decades. Although the substantial female predominance documented in early series remains true today, it has become clear that other so called ‘classical’ clinical features, such as symptoms of jaundice, pruritis and fatigue, and even biochemical markers of cholestasis, need not necessarily be present. Only a small minority of patients nowadays present with liver failure and most are even identified while asymptomatic, with up to 80% of patients in recently reported series having no PBC-related symptoms at the time of diagnosis, compared to only 4% some 30 years ago (Table 1).1–7 The diagnosis of PBC in asymptomatic patients is usually established after the chance finding of an abnormal physical sign, such as hepatomegaly, or, more often, an elevated serum alkaline phosphatase level during the course of an unrelated illness. Alternatively, patients may be diagnosed after biochemical or autoantibody, including anti-mitochondrial antibody (AMA), screening is carried out either as part of a routine health check or following the documentation of one of the many extrahepatic, predominantly autoimmune, disorders known to be associated with PBC. Crucial to the validity of diagnosing PBC on the basis of a positive AMA test in the latter circumstance is the finding that over 93% of AMA-positive yet asymptomatic patients with no biochemical evidence of cholestasis nonetheless have histological changes compatible with (or diagnostic of) PBC at liver biopsy.8 View this table: Table 1 Prevalence of symptoms at diagnosis of PBC Recognition of the extended clinical spectrum of PBC has resulted in a substantial increase in its reported prevalence, at least in some areas. Far from the historical view of PBC as an uncommon condition,9 recent studies from the north-east of England and Olmstead County in the US indicate that … Address correspondence to A/Professor S.M. Riordan, Gastrointestinal and Liver Unit, The Prince of Wales Hospital, Barker Street, Randwick 2031, New South Wales, Australia. email: riordans{at}sesahs.nsw.gov.au