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A 30-day course of prophylactic antibiotics added to standard treatment did not improve survival in patients hospitalized for severe alcohol-related hepatitis, researchers reported.

In a clinical trial of 292 patients, 2-month survival was not significantly different in those randomized to prednisone plus amoxicillin-clavulanate versus those who received prednisone and a placebo (17% vs 21%; HR 0.77, 95% CI 0.45-1.31, P=0.33), Philippe Mathurin, MD, of Hôpital Huriez in Lille, France, and colleagues reported in .

The infection rate at 2 months, however, was significantly lower in the antibiotic group (28% vs 42%; HR 0.62, 95% CI 0.41-0.91, P=0.02). Nevertheless, there were no significant differences in any other endpoints, including mortality at 90 and 180 days, incidence of hepatorenal syndrome, or Model for End-stage Liver Disease (MELD) or Lille scores, Mathurin's group said.

"The results of this study do not change the current protocol for the use of antibiotics, which should be prescribed only in patients with infection," the team concluded.

And the findings are consistent with those from previous smaller trials, according to the researchers. "Although prophylactic antibiotics did not improve outcomes in patients with alcohol-related hepatitis in this clinical trial, patients hospitalized for alcohol-related liver disease have a high risk of infection. Clinicians should identify infections as soon as possible and implement appropriate treatment to improve outcomes in patients with alcohol-related hepatitis."

In an , Ewan Forrest, MD, of the University of Glasgow in Scotland, and William Bernal, MD, of the University of London, said the study clarified two issues despite the negative findings.

The first is the role of sepsis: "The finding that antibiotics significantly reduced infection rates without improving liver function or preventing complications of liver failure is consistent with the hypothesis that sepsis is a consequence of severe alcohol-related hepatitis and/or its treatment, rather than the cause of worsening liver function," Forrest and Bernal wrote.

Secondly, the study clarified the significance of baseline infection treated prior to corticosteroid therapy, they said. "There was a suggestion of a role for antibiotics in those with baseline infection who are subsequently treated with corticosteroids."

A subgroup analysis of patients with infection prior to randomization, though not statistically significant, showed higher 2-month survival in those treated with amoxicillin-clavulanate (83.9% vs 65.0%; HR 0.40, 95% CI 0.13-1.16), Forrest and Bernal noted.

That finding is consistent with data reported from the , the largest randomized clinical trial of severe alcohol-related hepatitis, the editorialists said. In STOPAH, patients with baseline infections whose antibiotic treatment overlapped with corticosteroid treatment had significantly improved survival compared with those whose antibiotics were discontinued before corticosteroids were given.

These findings considered together "could suggest a clinically relevant role for the overlap of antibiotic treatment for baseline infection with the initiation of corticosteroids for ongoing alcohol-related hepatitis," Forrest and Bernal wrote.

Mean age of patients in the current study was 52, and 27% were women. All participants received 40 mg per day of oral prednisolone for 30 days. Those randomized to antibiotics received 1 g of amoxicillin and 125 mg of clavulanate three times daily for 30 days. Participants randomized to placebo received one placebo packet for oral suspension three times daily. Patients were evaluated in person weekly for the first 4 weeks and then at 45 days, 60 days, 3 months, and 6 months.

Study limitations, Mathurin and colleagues said, included that it lacked statistical power to detect smaller benefits in mortality -- it was hypothesized that mortality would be reduced by an absolute 14% in the antibiotic group, with an expected mortality rate of 27% for the placebo group. In addition, since infections were not formally adjudicated, it's possible there were misclassifications.

Finally, patient adherence to antibiotics was not rigorously determined. The researchers classified adherence as either "good" or "poor" without formal definitions, based on interviews with patients and diaries participants were asked to keep.

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