Fecal microbiota transplantation in alcohol-associated acute-on-chronic liver failure: an open-label clinical trial

Background Severe alcoholic hepatitis (SAH) presenting as acute-on-chronic liver failure (ACLF) carries a high short-term mortality. Alteration of gut microbiota is a crucial component implicated in its pathogenesis, whose modulation has been suggested as a potential therapeutic tool. We evaluated the safety of fecal microbiota transplantation (FMT) and its efficacy in improving short-term survival and clinical severity scores in patients with SAH-ACLF. Methods Thirty-three patients [13 in the FMT arm; 20 in the standard of care arm (SOC)] with SAH-ACLF were included in this open-label study. A single FMT session was administered as a freshly prepared stool suspension from pre-identified healthy family member stool donors through a nasojejunal tube. Patients were followed up on days 7, 28, and 90. Results Survival at 28 and 90 days was significantly better in the FMT arm (100% versus 60%, p =0.01; 53.84% versus 25%, p =0.02). Hepatic encephalopathy resolved in 100% versus 57.14% (FMT versus SOC, p =0.11) patients, while ascites resolved in 100% versus 40% survivors (p =0.04). Major adverse event rates, including spontaneous bacterial peritonitis and gastrointestinal bleeding, were similar in both groups (p= 0.77; p= 0.70). Median IL1beta decreased by 21.39% (IQR - 73.67 to 7.63) in the FMT group, whereas it increased in the SOC by 27.44% (IQR - 0.88 to 128.11) (p= 0.01). Percentage changes in bilirubin and ALT between baseline and day 7 emerged as predictors of 90-day mortality. Conclusion FMT is safe, improves short-term and medium-term survival, and leads to improvement in clinical severity scores in patients with SAH-ACLF. [GRAPHICS] .

Automated summary

Fecal microbiota transplantation (FMT) is safe and improves short-term and medium-term survival, as well as clinical severity scores, in patients with severe alcoholic hepatitis presenting as acute-on-chronic liver failure.