FMT Benefits Last a Few Years in Severe Alcoholic Hepatitis Patients

Patients with severe alcoholic hepatitis who underwent a fecal microbiota transplant (FMT) had lower rates of complications, alcohol relapse, and a trend towards improved survival 3 years later, a researcher said.

A small trial of 61 patients with biopsy-confirmed severe alcoholic hepatitis found that those treated with FMT had significantly less hepatic encephalopathy, critical infections, hospitalizations, and alcohol relapse than patients treated with corticosteroids, or standard of care, reported Cyriac Abby Philips, MD, of Rajagiri Hospital in Kochi, India.

Intestinal gut microbiome modulation via healthy donor FMT is shown to have preliminary benefits in various liver diseases, such as cirrhosis and chronic liver failure, as well as improved quality of life by promoting alcohol abstinence in patients with alcohol use disorder, he noted in a presentation at the American Association for the Study of Liver Diseases (AASLD) virtual meeting.

“But clinical outcomes in the long-term and gut microbiota changes in severe alcoholic hepatitis after FMT remain unknown,” Philips added.

When asked if he was surprised that the benefit lasted this long, Philips noted that studies on FMT for Clostridium difficile have shown durability for up to 3.8 years, which was in line with their findings here.

His group performed a retrospective examination of patients with severe alcoholic hepatitis from May 2017 to June 2018, who were treated with either FMT or corticosteroids, and had a response to steroids (“steroid responders”). Participants either completed the FMT protocol for 7 days or were administered corticosteroids daily for 28 days.

They measured clinical outcomes, such as liver, portal hypertension and extrahepatic events, and frequency of alcohol-use relapse. Survivors in both groups gave stool samples at baseline, at 1-2 years, and at 2-3 years.

Overall, 35 patients received FMT, while 26 received standard of care. Characteristics were similar between groups, with a mean age of about 47-51. Philips also noted bilirubin levels were significantly higher in the FMT group, but said that “most FMT patients were steroid-ineligible.”

There was no significant difference between groups at baseline in terms of ascites, hepatic encephalopathy, infections, acute kidney injury, or grades of acute chronic liver failure, he added.

At 3 years, significantly fewer patients treated with FMT experienced complications than those treated with standard of care, including:

• Hepatic encephalopathy: 20% vs 69% (P<0.001)
• Need for critical care: 43% vs 69% (P=0.04)
• Critical infections: 17% vs 54% (P=0.003)

In addition, significantly fewer patients in the FMT group experienced alcohol relapse versus standard of care (29% vs 54%, P=0.04), with a significantly longer time to relapse (436 days vs 197 days, P=0.002). However, Philips noted there was no difference in recurrence of alcohol-related hepatitis or cause of death between groups.

There was a trend towards higher 3-year survival rates in the FMT group, though it was not statistically significant. The survival curves did overlap, which Philips attributed to the fact that patients in both groups started out with alcohol abstinence.

He added that clinically relevant outcomes were associated with beneficial gut microbiota modulation in the FMT group, as pathogenic species were lower than in the standard of care group at 3 years follow-up.

Philips also acknowledged that the durability in results of FMT could be because the patients abstained from alcohol use, and it would be interesting to look at the changes in microbiota for patients who resumed drinking.

When other AASLD attendees pointed out that this was not a randomized trial, Philips acknowledged there were “multiple confounders” in this study, and stressed the need for larger, controlled studies about FMT in liver disease.

“Prospective controlled trials [can] see what other factors along with FMT actually work that improve clinical outcomes among patients,” he said.