Effect of Prophylactic Antibiotics on Mortality in Severe Alcohol-Related Hepatitis: A Randomized Clinical Trial

Area of Science:

• Hepatology
• Infectious Diseases
• Clinical Pharmacology

Background:

• Severe alcohol-related hepatitis poses significant mortality risks.
• The role of prophylactic antibiotics in managing this condition remains uncertain.
• Current treatment guidelines do not uniformly recommend antibiotics for severe alcoholic hepatitis.

Purpose of the Study:

• To evaluate the efficacy of amoxicillin-clavulanate plus prednisolone versus placebo plus prednisolone in reducing mortality for hospitalized patients with severe alcohol-related hepatitis.
• To assess the impact of prophylactic antibiotics on infection rates and other clinical outcomes in this patient population.

Main Methods:

• A multicenter, randomized, double-blind, placebo-controlled trial involving 292 patients with biopsy-proven severe alcohol-related hepatitis.
• Patients received either amoxicillin-clavulanate or placebo, in addition to prednisolone, with follow-up for 180 days.
• Primary outcome was all-cause mortality at 60 days; secondary outcomes included infection incidence and mortality at 90 and 180 days.

Main Results:

• No significant difference in 60-day all-cause mortality was observed between the amoxicillin-clavulanate group (17.3%) and the placebo group (21.3%).
• However, the incidence of infection at 60 days was significantly lower in the amoxicillin-clavulanate group (29.7%) compared to the placebo group (41.5%).
• No significant differences were found for other secondary outcomes, including 90- and 180-day mortality or hepatorenal syndrome incidence.

Conclusions:

• Amoxicillin-clavulanate, when added to prednisolone, does not improve survival in hospitalized patients with severe alcohol-related hepatitis.
• The findings do not support the routine use of prophylactic antibiotics to enhance survival in this patient group.
• While infections were reduced, this did not translate to improved overall mortality, highlighting the need for careful consideration of antibiotic use.