Primary Biliary Cirrhosis: Questions and Promises

The article on biochemical and histologic remission of primary biliary cirrhosis in response to medical treatment by Kaplan and colleagues [1] in this issue may be a landmark contribution. The authors force the reader to deal with a series of provocative issues, including redefinition of our understanding of the natural history of primary biliary cirrhosis and reevaluation of appropriate clinical end points for trials of treatment in this disease. They also raise the possibility that primary biliary cirrhosis is heterogeneous and should be further subtyped.

The natural history of primary biliary cirrhosis is extremely long and may extend over decades. An important paper [2] recently showed that patients who are positive for antimitochondrial antibody but have normal liver biochemical results will, with time, frequently develop clinically obvious primary biliary cirrhosis, thereby further extending the natural history of this disease backward in time. The disease is usually one of slow clinical progression. Most patients eventually develop such symptoms as pruritus or nonspecific fatigue. Overall patient survival is decreased, particularly when the disease is untreated. Various predictive models have been developed to help better assess patient prognosis; most of these models use bilirubin as a major component with or without histologic staging [3-5].

The histology of the disease is usually grouped into four categories that reflect the extent of inflammation within or away from the portal space, the degree of fibrosis, and the presence of cirrhosis [6]. The histologic progression through these stages …