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.

Changing compliance to the American College of Gastroenterology guidelines for the management of variceal hemorrhage: a regional survey.

OBJECTIVES: In mid-1997 the American College of Gastroenterology (ACG) published guidelines for the management of varices. The aim of this study is to assess the change in regional practice patterns between early 1997 (preguidelines) and 2000 (postguidelines). METHODS: Gastroenterologists in Oregon and Southwestern Washington state were sent a self-reporting questionnaire regarding the management of varices in March 1997 (prior to the publication of the guidelines) and again in August 2000. RESULTS: Fifty-seven of 75 (76%) and 68 of 92 (74%) of the surveys were completed in 1997 and 2000, respectively. Fifty to 60% of the respondents saw between three and five cirrhotic patients per month. Significantly, more respondents followed the guidelines to screen and treat large varices to prevent initial variceal hemorrhage in 2000 than in 1997, 54% versus 18% (p < 0.005). Of the respondents who performed screening of EGDs, the majority treated large varices with beta-blocker therapy (93% in 1997 and 97% in 2000). All respondents used early endoscopy to treat variceal bleeding. Significantly, most of the respondents began pharmacologic therapy prior to endoscopy if active variceal hemorrhage was suspected (with most choosing octreotide) in 2000 than in 1997, 83% versus 56% (p < 0.005). The majority of the respondents pursued repeat endoscopic therapy after cessation of the initial variceal bleeding episode (96% in 1997 and 95% in 2000), and most performed surveillance EGD once the varices had been eradicated (72% in 1997 and 79% in 2000). CONCLUSIONS: After the publication of the ACG guidelines, significantly more gastroenterologists screened for varices to prevent initial variceal hemorrhage and significantly more used pharmacologic therapy prior to endoscopic treatment for variceal hemorrhage.