At 60 days, survival among patients hospitalized with severe alcohol-related hepatitis was no higher with amoxicillin-clavulanate combined with prednisolone than with prednisolone alone, researchers report. “These results do not support prophylactic antibiotics to improve survival in patients hospitalized with severe alcohol-related hepatitis,” conclude the authors.
At 25 centers in France and Belgium in 2015–19, patients with biopsy-proven severe alcohol-related hepatitis (Maddrey function score ≥32 and Model for End-stage Liver Disease [MELD] score ≥21) were randomly assigned to prednisolone with amoxicillin-clavulanate or prednisolone combined with placebo. Patients were followed for 180 days.
Based on a primary outcome of all-cause mortality at 60 days, the authors found: “Among 292 randomized patients (mean age, 52.8 [SD, 9.2] years; 80 [27.4%] women) 284 (97%) were analyzed. There was no significant difference in 60-day mortality between participants randomized to amoxicillin-clavulanate and those randomized to placebo (17.3% in the amoxicillin-clavulanate group and 21.3% in the placebo group [P = .33]; between-group difference, −4.7% [95% CI, −14.0% to 4.7%]; hazard ratio, 0.77 [95% CI, 0.45-1.31]). Infection rates at 60 days were significantly lower in the amoxicillin-clavulanate group (29.7% vs 41.5%; mean difference, −11.8% [95% CI, −23.0% to −0.7%]; subhazard ratio, 0.62; [95% CI, 0.41-0.91]; P = .02). There were no significant differences in any of the remaining 3 secondary outcomes [all-cause mortality at 90 and 180 days; incidence of infection, incidence of hepatorenal syndrome, and proportion of participants with a MELD score less than 17 at 60 days; and proportion of patients with a Lille score less than 0.45 at 7 days]. The most common serious adverse events were related to liver failure (25 in the amoxicillin-clavulanate group and 20 in the placebo group), infections (23 in the amoxicillin-clavulanate group and 46 in the placebo group), and gastrointestinal disorders (15 in the amoxicillin-clavulanate group and 21 in the placebo group).”
Editorial: “For patients with alcohol-related hepatitis, developing infection while taking corticosteroids is an indicator of poor prognosis and should be treated,” editorialists write. “This may be particularly relevant for patients without a Lille score biochemical response to corticosteroids, since these patients have an increased rate of infection compared with those with a biochemical response…. Guidelines recommend discontinuation of corticosteroids for patients who do not show biochemical response to treatment as reflected by the Lille score, but close monitoring for infection and early institution of antibiotic therapy for documented infection should continue, as the risk of infection, especially lung infection, remains high even after corticosteroid therapy is discontinued. In addition, clinicians should evaluate all patients with alcohol-related hepatitis for infection, and treat identified infections, prior to initiating corticosteroids as recommended in the American College of Gastroenterology guidelines for the management of alcohol-related liver disease. If there are features of active ongoing alcohol-related hepatitis after treatment of baseline infection, then overlapping the antibiotic treatment with subsequent corticosteroid therapy could be considered.”