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Abstract Details
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.
1Université Lille, CHU de Lille, Service des maladies de l'appareil digestif, Hôpital Huriez, INFINITE-U1286, Lille, France.
2Unité de biostatistiques, CHU de Lille, Lille, France.
3Service d'hépato-gastroentérologie, CHU de Caen, Caen, France.
4Service d'hépatologie, Hôpital Jean-Minjoz, CHU de Besançon, Besançon, France.
5Service d'hépato-gastroentérologie, CHU d'Angers, Angers, France.
6Service d'hépatologie, CHU de Toulouse, Toulouse, France.
7Service d'hépato-gastroentérologie, Hôpital de Dunkerque, Dunkerque, France.
8Service d'hépato-gastroentérologie, CHU d'Amiens, Amiens, France.
9Service d'hépato-gastroentérologie, CHU de Dijon, Dijon, France.
10Service d'hépato-gastroentérologie, CHU de Reims, Reims, France.
11Service d'hépato-gastroentérologie, CHU de Nice, Nice, France.
12Service d'hépato-gastroentérologie, Hôpital de Valenciennes, Valenciennes, France.
13Service d'hépatologie, Hôpital Saint-Antoine, Paris, France.
14Service d'hépatologie, Hôpital Saint-Eloi, CHU de Montpellier, Montpellier, France.
15Service d'hépato-gastroentérologie, CHU de Grenoble, Grenoble, France.
16Service des maladies du foie, Hôpital Pontchaillou, Rennes, Rennes, France.
17Service d'hépato-gastroentérologie, Hôpital Jean-Verdier, Bondy, France.
18Unité de pharmacovigilance, CHU de Lille, Lille, France.
Abstract
Importance: The benefits of prophylactic antibiotics for hospitalized patients with severe alcohol-related hepatitis are unclear.
Objective: To determine the efficacy of amoxicillin-clavulanate, compared with placebo, on mortality in patients hospitalized with severe alcohol-related hepatitis and treated with prednisolone.
Design, setting, and participants: Multicenter, randomized, double-blind clinical trial among patients with biopsy-proven severe alcohol-related hepatitis (Maddrey function score ≥32 and Model for End-stage Liver Disease [MELD] score ≥21) from June 13, 2015, to May 24, 2019, in 25 centers in France and Belgium. All patients were followed up for 180 days. Final follow-up occurred on November 19, 2019.
Intervention: Patients were randomly assigned (1:1 allocation) to receive prednisolone combined with amoxicillin-clavulanate (n = 145) or prednisolone combined with placebo (n = 147).
Main outcome and measures: The primary outcome was all-cause mortality at 60 days. Secondary outcomes were 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.
Results: 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. 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).
Conclusion and relevance: In patients hospitalized with severe alcohol-related hepatitis, amoxicillin-clavulanate combined with prednisolone did not improve 2-month survival compared with prednisolone alone. These results do not support prophylactic antibiotics to improve survival in patients hospitalized with severe alcohol-related hepatitis.
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