Effect of rifaximin on infections, acute‐on‐chronic liver failure and mortality in alcoholic hepatitis: A pilot study (RIFA‐AH)

Abstract

Background & Aims Alcoholic hepatitis (AH) is associated with a high incidence of infection and mortality. Rifaximin reduces bacterial overgrowth and translocation. We aimed to study whether the administration of rifaximin as an adjuvant treatment to corticosteroids decreases the number of bacterial infections at 90 days in patients with severe AH compared to a control cohort. Methods This was a multicentre, open, comparative pilot study of the addition of rifaximin (1200 mg/day/90 days) to the standard treatment for severe AH. The results were compared with a carefully matched historical cohort of patients treated with standard therapy and matching by age and model of end‐stage liver disease (MELD). We evaluated bacterial infections, liver‐related complications, mortality and liver function tests after 90 days. Results Twenty‐one and 42 patients were included in the rifaximin and control groups respectively. No significant baseline differences were found between groups. The mean number of infections per patient was 0.29 and 0.62 in the rifaximin and control groups, respectively (p = .049), with a lower incidence of acute‐on‐chronic liver failure (ACLF) linked to infections within the treatment group. Liver‐related complications were lower within the rifaximin group (0.43 vs. 1.26 complications/patient respectively) (p = .01). Mortality was lower in the treated versus the control groups (14.2% vs. 30.9, p = .15) without significant differences. No serious adverse events were associated with rifaximin treatment. Conclusions Rifaximin is safe in severe AH with a significant reduction in clinical complications. A lower number of infections and a trend towards a lower ACLF and mortality favours its use in these patients.

Effect of Prophylactic Antibiotics on Mortality in Severe Alcohol-Related Hepatitis

“…In a randomized clinical trial of 32 patients with alcohol-related hepatitis, prophylactic antibiotic therapy with rifaximin for 4 weeks did not significantly improve inflammatory markers and amino acid measures compared with standard medical treatment . A case-control study of 21 patients with alcohol-related hepatitis treated with rifaximin reported a lower incidence of infection compared with 42 control patients at 90-day follow-up, but there was no survival benefit …”

Role of rifaximin in the management of alcohol‐associated hepatitis: A systematic review and meta‐analysis

“…Three studies, including two RCTs and one case-control study, were included in the final meta-analysis. [18][19][20] Of a total of 162 patients, 69% were male. Baseline study population characteristics, including median patient age, MELD, and MDF, as well as treatment regimens are reported in Tables 4 and 5.…”

“…In the non-rifaximin group, 18 out of the 42 patients developed a total of 26 infections, 8 of which progressed to sepsis, including 7 urinary tract infections, 6 spontaneous bacteremias, 5 spontaneous bacterial peritonitis, 5 pneumonias, 2 colitis, and 1 cellulitis. 18,20 90-day mortality. There was no significant difference in 90-day mortality rate between the rifaximin versus non-rifaximin group (RR: 0.743, 95% CI: 0.298-1.850, I 2 = 24%, P = 0.523) (Fig.…”

Narrative Review: Glucocorticoids in Alcoholic Hepatitis—Benefits, Side Effects, and Mechanisms

“…GR in hepatocytes likely has a major role in regulating neutrophil homeostasis via differentially regulating CXCL1, CXCL2, and CXCL8. A recent pilot study shows that co-treatment of sAH patients with GC and the antibiotic rifaximin is safe, with a reduction in liver-related complications and infections compared with a historical cohort [ 240 ]. The increase in the aldosterone/MR pathway is associated with increased alcohol drinking in patients with alcohol use disorders [ 241 ], and MR antagonists inhibit alcohol self-administration in rats [ 242 ].…”