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

Sharma, Anshu; Roy, Akash; Premkumar, Madhumita; Verma, Nipun; Duseja, Ajay; Taneja, Sunil; Grover, Sandeep; Chopra, Madhu; Dhiman, Radha K.

doi:10.1007/s12072-022-10312-z

Cited by 49 publications

(27 citation statements)

References 32 publications

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“…The survival rates in ACLF patients with higher grades at the end of 548 days was 58.3%, demonstrating proof of concept on the benefits of FMT in this very sick group with SAH-related ACLF [ 18 ]. Similarly, a recent study from India by researchers at the Post Graduate Institute, Chandigarh also validated findings that FMT was safe, improved short-term and medium-term survival, and led to improvement in clinical severity scores in patients [ 19 ]. Bajaj et al .…”

Section: Discussionmentioning

confidence: 63%

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

Philips

Ahamed

Rajesh

et al. 2022

Gastroenterology Report

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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.

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Section: Discussionmentioning

confidence: 63%

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

Philips

Ahamed

Rajesh

et al. 2022

Gastroenterology Report

View full text Add to dashboard Cite

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Section: Impact Of Fmt On Alcohol-associated Hepatitismentioning

confidence: 99%

Gut Microbiome-Centered Therapies for Alcohol-Associated Liver Disease

Ranjbarian,

Schnabl

2023

Semin Liver Dis

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Globally, liver disease caused by alcohol is becoming more prevalent each year. Misuse of alcohol causes a spectrum of liver diseases, such as liver steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The cornerstone of treatment is abstinence from alcohol. In spite of this, available treatment for alcohol-associated liver disease (ALD) shows limited effectiveness at the present time. There are numerous ways in which alcohol disrupts the gut-liver axis, including dysbiosis of the gut microbiome, disruption of mucus and epithelial cell barriers, impaired production of antimicrobial molecules, and dysfunction of the immune system, causing translocation of viable microbes and microbial products to the liver and systemic circulation. Microbial exposure not only results in inflammation and progression of liver disease, but also infections in late stage ALD. This led scientists to focus their therapeutic strategies and targets for ALD on the gut microbiome. Throughout this review, we address the role of gut microbiome centered therapeutic approaches for ALD focusing predominantly on randomized controlled trials. We will summarize the latest clinical trials using probiotics, antibiotics, fecal microbial transplants in modulating the gut liver axis and for improvement of ALD.

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“…Fecal microbiota transplantation (FMT), which involves the transfer of donor stool into recipients, is increasingly being explored as a potential treatment in gastric intestinal and liver diseases [191]. Clinical trials supported the safety of FMT and have shown improvement of survival and clinical severity in patients with severe alcoholic hepatitis [192,193]. However, FMT can be lethal for elderly people because of serious compli-cations, such as infections from multidrug-resistant organisms [194].…”

Section: Microbiological Therapymentioning

confidence: 99%

The Roles of Myeloid Cells in Aging-related Liver Diseases

Yao¹,

Li²,

Wang³

2023

Int. J. Biol. Sci.

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Aging is a necessary process of life associated with various mechanisms, such as genomic instability, loss of proteostasis, deregulated nutrient sensing, and cellular senescence, causing progressive dysregulation of the microenvironment, organ homeostasis and biological functions. The hepatic microenvironment is essential for maintaining liver homeostasis, in which hepatocytes, sinusoidal endothelial cells, stellate cells and immune cells are closely associated with the development of aging-related liver diseases. There is increasing evidence that immunocytes, especially myeloid cells, are involved in aging-related liver diseases such as alcoholic liver disease, nonalcoholic liver disease, liver fibrosis or cirrhosis and liver cancer, becoming promising treatment targets of these diseases. This review summarizes the phenotypic and functional alterations associated with aging liver and myeloid cells, as well as the roles of myeloid cells in the progression of aging-related liver diseases.

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

Cited by 49 publications

References 32 publications

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

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

Gut Microbiome-Centered Therapies for Alcohol-Associated Liver Disease

The Roles of Myeloid Cells in Aging-related Liver Diseases

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