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Prophylactic Antibiotics for Alcohol-Related Hepatitis?

June 8, 2023

Written by Millie Cosse

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Prophylactic treatment of patients with severe alcohol-related hepatitis with amoxicillin-clavulanate did not reduce all-cause mortality when compared to placebo.

Why does this matter?
Animal studies have previously demonstrated that antibiotics may improve hepatic function by reducing liver inflammation, but this phenomenon had not yet been studied in humans.

 A tough pill to swallow
This multicenter, randomized, double-blind clinical trial of 292 patients with biopsy-proven severe alcohol-related hepatitis evaluated the effect of amoxicillin-clavulanate plus prednisolone versus placebo plus prednisolone on mortality in hospitalized patients. The primary outcome was all-cause mortality at 60 days, and investigators also examined all-cause mortality at 90 and 180 days, incidence of infection, incidence of hepatorenal syndrome, and MELD score at 60 days.

The rate of all-cause mortality at 60-days was 17.3% in antibiotic group and 21.9% in placebo group, which represents a hazard ratio of 0.77 (95%CI 0.45-1.31). Similarly, there was no significant difference in 90-day and 180-day all-cause mortality between the two groups. These findings are consistent with two prior randomized trials that evaluated prophylactic antibiotic therapy for severe alcoholic hepatitis.

However, there was a significant reduction in infection rates at 60 days among the antibiotic group (29.7% vs 41.5%; 95%CI −23.0% to −0.7%). No significant differences were found in the remaining secondary outcomes.

My take: These patients are at greatly increased risk of infection and are likely to need antibiotics at some point during their hospitalization, but prophylactic antibiotics do not seem to have a role in the treatment of adults with severe alcohol-related hepatitis.

Effect of Prophylactic Antibiotics on Mortality in Severe Alcohol-Related Hepatitis: A Randomized Clinical Trial. JAMA. 2023 May 9;329(18):1558-1566. doi: 10.1001/jama.2023.4902.

What are your thoughts?