| The Role of Fecal Microbiota Transplantation in the Treatment of Liver Diseases


The Role of Fecal Microbiota Transplantation in the Treatment of Liver Diseases

Chathur Acharya, MD and Jasmohan S. Bajaj, MD, MS

With the emerging role of the gut microbiome in gastroenterology and liver disease, there has been a substantial interest in using FMT in hepatology as a potential therapeutic intervention. Over the past 5 years there have been promising data generated to support this avenue, and there are many more studies underway. The FDA has not approved FMT as a therapeutic option for chronic liver disease. This section will examine current and emerging data for FMT in different liver conditions.

Preclinical Evidence for Fecal Microbiota Transplantation in Liver Disease

There have been investigations into the use of FMT to treat liver disease in rodent models. Zhou et al1 reported a study of autologous FMT daily for 8 weeks in mice with high-fat diet–induced nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and demonstrated that FMT improved steatohepatitis and systemic inflammation. Another study in acute liver failure–related hepatic encephalopathy demonstrated that duodenally infused FMT daily for 3 weeks resulted in improved behavior, memory, and learning and reduced systemic inflammation.2 This study was limited by the lack of microbiome assessments pre- and post-FMT.2 In alcoholic liver disease models, when FMT was performed with FMT material from alcohol-resistant donor mice, FMT restored the intestinal microbiota composition to that of the donor mice. Additionally, the treatment prevented alcohol-induced gut barrier changes and also prevented the development of liver disease related to alcohol.3 Overall, preclinical work suggests that FMT is a promising intervention for various microbiome-mediated liver diseases.

Fecal Microbiota Transplantation Clinical Trials in Humans

Given the promising preclinical work, a number of investigators have begun to examine to role of FMT in humans with various liver diseases.

Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is a rare, progressive cholestatic liver disease, notable for leading to bile duct strictures, and often linked with IBD. Currently, no FDA- or European Medicines Agency (EMA)–approved therapies exist for this indication, and patients may ultimately require liver transplantation. Allegretti et al4 conducted a Phase 1b pilot open-label study of 10 patients with early-stage PSC with concomitant IBD. Patients underwent a single FMT by colonoscopy (90 mL) from a single healthy donor. The primary objective was safety and feasibility. The treatment was well-tolerated, and no patients experienced a treatment-related serious adverse event. Overall, 30% (3/10) of patients had improvement of 50% or greater alkaline phosphatase levels, a key biliary biomarker in PSC. Microbial diversity of the patients resembled the donor within 1 week and was sustained through the end of the study (6 months).4 Given the unmet medical need for this disease, FMT remains a promising therapy and requires further study (Figure 10.3-1).

Alcoholic Hepatitis

Alcoholic hepatitis is characterized by inflammation in the liver post-excessive alcohol consumption. It has been suggested that alcohol consumption can lead to dysbiosis, and this alteration of the gut microbiome may propagate the disease.

In a study of patients with severe alcoholic hepatitis, FMT was compared with other standard-of-care (SOC) interventions. Among 51 patients enrolled, 16 were treated with FMT. Overall, patients who received FMT had the highest survival rates at 1 and 3 months. Specifically, the proportions of patients surviving at the end of 1 and 3 months in the steroids, nutrition, pentoxifylline, and FMT arms were 63%, 47%, 40%, and 75% (P = .179) and 38%, 29%, 30%, and 75% (P = .036), respectively. Following FMT, significant beneficial changes in the microbiome were noted.

A number of studies, including randomized clinical trials, are actively recruiting at the time of writing (NCT03091010 [open label, nasojejunal], NCT03827772 [open label, nasojejunal], and NCT03416751 [randomized clinical trial, enema]). These studies highlight the interest in and promise of FMT in alcoholic hepatitis.

Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis

NAFLD is characterized by fat deposition or hepatic steatosis (> 5%) without secondary causes. It is often associated with other metabolic conditions, such as diabetes mellitus, obesity, and metabolic syndrome. NASH is separately defined as the presence of at least 5% hepatic steatosis with inflammation and the addition of hepatocyte injury with or without fibrosis.5 This can progress to cirrhosis and has become the leading cause of liver transplantation in the United States. There are no FDA- or EMA-approved therapies currently. Given the promising preclinical data previously described, there is interest in the use of FMT to restore the microbiome in patients with NAFLD/NASH.

Xue et al6 reported a pilot placebo-controlled trial (N = 47) of FMT in NAFLD. The primary outcome assessed was change in fat attenuation parameter assessed by FibroTouch. They demonstrated that patients in the FMT arm had significant reduction in fat attenuation parameter compared with the control group. Spe cifically, the FMT arm had a mean decrease of 9.26 ± 29.31 compared with an increase of 12.21 ± 24.48 in the control arm (P = .038).6

Parvathy et al7 performed a pilot randomized clinical trial using FMT via upper endoscopy compared with autologous FMT in patients with NAFLD. Overall, they did not report any related serious adverse events and demonstrated improvement in small intestinal permeability biomarkers.7


Figure 10.3-1. Fecal microbiota transplantation for the treatment of primary sclerosing cholangitis.4 (ALP = alkaline phosphate; OTU = operational taxonomical unit.)

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

May 23, 2021 | Posted by in GASTROENTEROLOGY | Comments Off on | The Role of Fecal Microbiota Transplantation in the Treatment of Liver Diseases

Full access? Get Clinical Tree

Get Clinical Tree app for offline access