Differences between Caucasian, African American, and Hispanic patients with primary biliary cirrhosis in the United States.

UNLABELLED: Primary biliary cirrhosis (PBC) is an uncommon chronic cholestatic liver disease that primarily afflicts young and middle-aged Caucasian women; there are limited data on the clinical presentation and disease severity among non-Caucasian patients with this disease. The goal of this study was to examine differences in the severity of liver disease between Caucasian and non-Caucasian patients with PBC screened for enrollment in a large national multicenter clinical trial. Demographic features, symptoms, physical findings, and laboratory tests obtained during screening were examined in 535 patients with PBC with respect to ethnicity, gender, and antimitochondrial antibody (AMA) status; 73 of 535 (13.6%) were non-Caucasian (21 were African American, and 42 were Hispanic). Non-Caucasians were more likely than Caucasians to be ineligible for participation in the clinical trial (46.5% versus 25.1%, P = 0.0001), primarily because of greater disease severity. African Americans and Hispanics were also more likely to have a lower activity level, more severe pruritus, and more advanced disease. However, the mean age, male-to-female ratio, and seroprevalence of AMA positivity were similar between the 2 groups. CONCLUSION: Liver disease severity at clinical presentation is higher among non-Caucasians than Caucasians with PBC, and this cannot be explained by demographic or serologic features alone. Possible mechanisms underlying this health discrepancy are not clear, but increased awareness of PBC as a cause of chronic cholestatic liver disease is critical in evaluating non-Caucasian patients in the United States.

Methotrexate (MTX) plus ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis.

This placebo-controlled, randomized, multicenter trial compared the effects of MTX plus UDCA to UDCA alone on the course of primary biliary cirrhosis (PBC). Two hundred and sixty five AMA positive patients without ascites, variceal bleeding, or encephalopathy; a serum bilirubin less than 3 mg/dL; serum albumin 3 g/dL or greater, who had taken UDCA 15 mg/kg daily for at least 6 months, were stratified by Ludwig's histological staging and then randomized to MTX 15 mg/m2 body surface area (maximum dose 20 mg) once a week while continuing on UDCA. The median time from randomization to closure of the study was 7.6 years (range: 4.6-8.8 years). Treatment failure was defined as death without liver transplantation; transplantation; variceal bleeding; development of ascites, encephalopathy, or varices; a doubling of serum bilirubin to 2.5 mg/dL or greater; a fall in serum albumin to 2.5 g/dL or less; histological progression by at least two stages or to cirrhosis. Patients were continued on treatment despite failure of treatment, unless transplantation ensued, drug toxicity necessitated withdrawal, or the patient developed a cancer. There were no significant differences in these parameters nor to the time of development of treatment failures observed for patients taking UDCA plus MTX, or UDCA plus placebo. The trial was conducted with a stopping rule, and was stopped early by the National Institutes of Health at the advice of our Data Safety Monitoring Board for reasons of futility. In conclusion, methotrexate when added to UDCA for a median period of 7.6 years had no effect on the course of PBC treated with UDCA alone.