Carvedilol fails to reduce variceal bleeds in acute-on-chronic liver failure
WASHINGTON – Treatment with carvedilol reduced the incidence of sepsis and acute kidney injury and improved survival at 28 days but did not significantly reduce the progression of esophageal varices in patients with acute-on-chronic liver failure.
A total of 136 patients with acute-on-chronic liver failure with small or no esophageal varices and a hepatic venous pressure gradient (HVPG) of 12 mm Hg or greater were enrolled in a single center, prospective, open-label, randomized controlled trial: 66 were randomized to carvedilol and 70 to placebo, according to Sumeet Kainth, MD, of the Institute of Liver and Biliary Sciences in New Delhi.
Dr. Sumeet Kainth
More than 90% of patients were men with a mean age of 44 years, and composition of the treatment and placebo groups was similar. About 70% in each group had alcoholic hepatitis (the reason for acute liver failure in most). Mean Model for End-Stage Liver Disease (MELD) scores were about 25. Hemodynamic parameters also were comparable, with a mean HVPG of about 19, Dr. Kainth said at the annual meeting of the American Association for the Study of Liver Diseases.
Patients in the treatment group received a median maximum tolerated dose of carvedilol of 12.5 mg, with a range of 3.13 mg to 25 mg.
Morbidity and mortality were high, as is expected with acute-on-chronic liver failure, he noted. A total of 36 patients died before the end of the 90-day study period. Another 23 experienced adverse events and 2 progressed to liver transplant.
HVPG at 90 days decreased significantly in both groups. In the carvedilol group, 90-day HVPG was 16 mm Hg, compared with 19.7 mm Hg at baseline (P less than .01). For placebo patients, 90-day HVPG spontaneously improved to 14.8 mm Hg, compared with a baseline of 17.2 mm Hg (P less than .01).
Carvedilol did not significantly slow the development or growth of varices, however, Dr. Kainth said. At 90 days, varices had progressed in 9 of 40 patients (22.5%) of patients on carvedilol and 8 of 31 (25.8%) of placebo patients.
Significantly fewer patients in the carvedilol group developed acute kidney injury at 28 days (14% vs. 38% on placebo) and sepsis (5% vs. 20%). Mortality also was reduced significantly at 28 days (11% vs. 24%), he reported.
Treatment with carvedilol did not achieve significant reductions in variceal bleeding, “possibly due to the low number of bleeds seen in the study [because of] the exclusion of patients with large varices,” Dr. Kainth said.
The study was sponsored by Institute of Liver and Biliary Sciences. Dr. Kainth reported no relevant conflicts of interest.
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