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. 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. It is interesting that Kaplan and colleagues found florid duct lesions in two of the three patients with biochemical normalization and histologic improvement. It is also important to note that sampling variation is definitely seen in liver biopsy samples of patients with primary biliary cirrhosis. The issue of sampling variation must be carefully considered in interpreting Kaplan and colleagues' results. Several therapeutic options have been studied and are now available to patients with primary biliary cirrhosis.