Time course of histological progression in primary biliary cirrhosis.

Histological staging is used for stratification and assessment of treatment efficacy in therapeutic trials for primary biliary cirrhosis (PBC). Knowledge of the rate of progression of the histological changes would be helpful in the design (duration) and conduct of clinical trials. The histological stages were recorded for liver biopsies performed annually on 222 patients during a randomized, placebo-controlled clinical trial in which therapy with D-penicillamine (DPCA) was shown to be ineffective. These data were analyzed using a Markov model to describe the time course of histological progression in PBC. At study entry, 15 patients were stage I, 56 were stage II, 96 were stage III, and 55 were stage IV. Histological progression was observed after 1 year in 41%, 43%, and 35% of the patients, and after 2 years in 62%, 62%, and 50% of the patients who were stage I, stage II, and stage III at entry, respectively. After 4 years biopsies showed cirrhosis in 31% and 50% of the patients in stage I and stage II at entry, respectively. A minority (20%) of the precirrhotic patients showed histological stability; sustained histological regression was rarely observed (2%). Our data suggest that a majority of patients with PBC will progress histologically within 2 years. The distribution of histological stages over time may be helpful in determining the number of patients and length of time necessary to appreciate a treatment effect on histological progression in clinical trials for PBC.