Clinical outcomes and gut microbiota analysis of severe alcohol-associated hepatitis patients undergoing healthy donor fecal transplant or pentoxifylline therapy: single-center experience from Kerala

Cyriac Abby Philips; Rizwan Ahamed; Sasidharan Rajesh; Shobhit Singh; Ajit Tharakan; Jinsha K Abduljaleel; Philip Augustine

doi:10.1093/gastro/goac074

Clinical outcomes and gut microbiota analysis of severe alcohol-associated hepatitis patients undergoing healthy donor fecal transplant or pentoxifylline therapy: single-center experience from Kerala

Gastroenterol Rep (Oxf). 2022 Dec 5:10:goac074. doi: 10.1093/gastro/goac074. eCollection 2022.

Authors

Cyriac Abby Philips^{1

2}, Rizwan Ahamed³, Sasidharan Rajesh⁴, Shobhit Singh⁴, Ajit Tharakan³, Jinsha K Abduljaleel³, Philip Augustine^{2

3}

Affiliations

¹ Clinical and Translational Hepatology, The Liver Institute, Center of Excellence in GI Sciences, Rajagiri Hospital, Chunangamvely, Aluva, Ernakulam, Kerala, India.
² Monarch Liver Laboratory, The Liver Institute, Center of Excellence in GI Sciences, Rajagiri Hospital, Chunangamvely, Aluva, Ernakulam, Kerala, India.
³ Department of Gastroenterology and Advanced GI Endoscopy, Center of Excellence in GI Sciences, Rajagiri Hospital, Chunangamvely, Aluva, Ernakulam, Kerala, India.
⁴ Diagnostic and Interventional Radiology, Center of Excellence in GI Sciences, Rajagiri Hospital, Chunangamvely, Aluva, Ernakulam, Kerala, India.

Abstract

Background: Severe alcohol-associated hepatitis (SAH) patients with infections have a high short-term mortality rate. Gut microbiota dysbiosis plays an important role in the pathogenesis of SAH. Preliminary studies have demonstrated long-term benefits with healthy donor fecal microbiota transplantation (FMT). Data on FMT compared with pentoxifylline for SAH and relevant gut microbial changes are lacking in literature.

Methods: From January 2019 to February 2021, retrospective analysis of a single hospital's records revealed 47 SAH patients undergoing FMT (100 mL/day via nasoduodenal tube for 7 days) and 25 matched patients receiving pentoxifylline (400 mg/8 h for 28 days). The primary end point was a 6-month survival rate. Secondary end points included incidence of ascites, hepatic encephalopathy, infections, acute kidney injury, and gut microbiota changes between post-therapy groups. Biomarker discovery and network analysis were also performed to identify significant taxa of gut microbiota in post-treatment groups in retrospectively stored stool samples.

Results: All were males. The 6-month survival rate was higher in the patients undergoing FMT than in patients receiving pentoxifylline (83.0% vs 56.0%, P = 0.012). At the end of 6-month follow-up, the incidences of clinically significant ascites (56.0% vs 25.5%, P = 0.011), hepatic encephalopathy (40.0% vs 10.6%, P = 0.003), and critical infections (52.0% vs 14.9%, P < 0.001) in patients administered pentoxifylline were significantly higher than those in patients treated with FMT. At 3 months, biomarker analysis revealed a significant abundance of Bifidobacterium and Eggerthella in the FMT group and the pentoxifylline group, respectively. At 6 months, Bifidobacterium in the FMT group and pathogenic Aerococcaceae in the pentoxifylline group were notable. Network analysis showed beneficial taxa (Bifidobacterium) as a central influencer in those undergoing FMT at 6 months.

Conclusions: Healthy donor FMT improved survival rate and reduced liver-related complications compared with pentoxifylline. These clinical benefits were associated with favorable modulation of intestinal bacterial communities. Difficult-to-treat SAH patients may be safely bridged to transplantation using FMT. Controlled trials evaluating long-term outcomes are an unmet need.

Keywords: alcoholic hepatitis; dysbiosis; fecal microbiota; liver transplant; stool transplant.