Survival and symptom progression in a geographically based cohort of patients with primary biliary cirrhosis: Follow-up for up to 28 years

Background & Aims: Although several excellent studies have described the natural history of primary biliary cirrhosis, most were reported from tertiary referral centers. We examined the prognosis of primary billary cirrhosis in a comprehensive geographically defined cohort. Methods: We followed up 770 primary biliary cirrhosis patients prevalent between January 1987 and December 1994 until death, transplantation, or censor on January 1, 2000, by interview and review of case notes and death certificates. Analysis of survival data was performed with Kaplan-Meier methods and Cox regression. Results: Median patient survival was 9.3 years from diagnosis. Patient age, alkaline phosphatase, albumin, and bilirubin at diagnosis independently predicted survival in Cox modeling. Prothrombin time and histologic stage did not independently affect survival. Observed survival was predicted well by this model and by the Mayo prognostic score (R-M(2) = 0.37 and 0.18, respectively; R-M(2) is a likelihood-based measure of the percentage information gain from the model due to covariates). Forty-two percent of deaths were caused by liver disease. Thirty-nine patients had liver transplantations by the censor date. Survival was much poorer than for an age- and sex-matched control population (standardized mortality ratio = 2.87 [1.73 excluding liver deaths]). The most common symptoms at diagnosis were pruritus (18.9%) and fatigue (21.0%). Twenty-six percent of patients developed liver failure by 10 years after diagnosis. Conclusions: Although primary biliary cirrhosis is often now diagnosed at an early stage, the diagnosis still carries important prognostic implications. A significant proportion of patients develop liver failure, require transplantation, or die prematurely after this diagnosis.