Adding prophylactic antibiotic therapy to prednisolone does not improve survival in patients hospitalized with severe alcohol-related hepatitis, new research shows.
In a double-blind randomized clinical trial, amoxicillin-clavulanate added to prednisolone did not significantly reduce all-cause mortality at 60 days compared with prednisolone alone.
Antibiotic therapy did reduce the rate of infection but had no impact on five other secondary outcomes.
“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,” write the authors, led by Alexandre Louvet, MD, with Université de Lille and Hôpital Claude Huriez, Lille, France.
“Clinicians should identify infections as soon as possible and implement appropriate treatment to improve outcomes in patients with alcohol-related hepatitis,” the researchers add.
The results of the AntibioCor trial were published online in JAMA.
Study Details
The benefits of prophylactic antibiotics in cases of severe alcohol-related hepatitis remain unclear.
The AntibioCor trial enrolled 292 patients (mean age, 53 years) with biopsy-proven severe alcohol-related hepatitis (Maddrey function score ≥ 32 and Model for End-stage Liver Disease [MELD] score ≥ 21) from 25 centers in France and Belgium.
All participants received 40 mg/d of oral prednisolone for 30 days plus 1 g amoxicillin and 125 mg clavulanate or matching placebo three times daily for 30 days.
There was no significant difference in the primary outcome of all-cause mortality at 60 days between the antibiotic group and the placebo group (17.3% vs 21.3%; hazard ratio [HR], 0.77; P = .33).
Antibiotic therapy also had no significant effect on the secondary outcomes of 90- and 180-day mortality, incidence of hepatorenal syndrome, and the proportion of participants with a MELD score < 17 at 60 days and Lille scores < 0.45 at 7 days.
However, the infection rate at 60 days was significantly lower in the antibiotic group (29.7% vs 41.5%; HR, 0.62; P = .02).
Two Issues Clarified
This study suggests “no role for prophylactic prescription of antibiotics when treating all patients who have alcohol-related hepatitis with corticosteroids,” write Ewan Forrest, MD, with Glasgow Royal Infirmary, Scotland, and William Bernal, MD, with Kings College Hospital, London, England, in a linked editorial.
“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,” they say.
Forrest and Bernal add that this study does help clarify two issues.
The first pertains to 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,” they write.
The study also clarifies the significance of baseline infection treated before initiation of corticosteroid therapy, Forrest and Bernal say.
They note that, although not statistically significant, in the subgroup of patients with infection before randomization, antibiotic therapy was associated with a higher 60-day survival.
Considered together with other data, “this 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 say.
“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,” they add.
The AntibioCor trial study was funded by the French Ministry of Health and supported by an unrestricted grant from the Programme Hospitalier de Recherche Clinique 2013 to CHU de Lille. Louvet reports no relevant disclosures. Bernal has received personal fees from Versantis AG and Flagship Pioneering. Forrest reports no relevant disclosures.
JAMA. Published online May 9, 2023. Abstract; Editorial
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