FMT may prevent hepatic encephalopathy recurrence in cirrhosis patients

A phase II study has demonstrated the safety of faecal microbiota transplantation (FMT) in patients with cirrhosis treated with lactulose and rifaximin, with no related adverse events (AEs) seen. FMT also results in lower rates of hepatic encephalopathy (HE) recurrence.

On post hoc analysis, HE recurrence occurred most frequently in the placebo-only groups and correlated with lower baseline Lachnospiraceae and reduced donor engraftment.

Sixty patients with cirrhosis and HE on maximal therapy were randomized into four groups: three active doses; two active and one placebo dose; one active and two placebo doses; three placebo doses. They received two capsules and one enema (either placebo or FMT) and were followed for 6 months.

Baseline characteristics did not differ across treatment groups. FMT showed a favourable safety profile, with no FMT-related AEs and serious (S)AEs reported. Overall SAEs (p=0.96) or death (p=1.0) were similar, but HE recurrence differed substantially between groups (Cramer’s V=0.39; p=0.035). [J Hepatol 2025;83:81-91]

Post hoc analysis revealed the highest recurrence rate in the all-placebo group compared with any FMT group (40 percent vs 9 percent; odds ratio, 0.15, 95 percent confidence interval, 0.04‒0.64). The rates of HE recurrence within the FMT groups were comparable regardless of route, doses, or donor type.

Patients who received FMT also showed improvements in quality of life. Additionally, engraftment was highest in patients with high pre-FMT Lachnospiraceae and lower in those with HE recurrence.

“While the phase II trial was not powered for individual subgroup comparison, the results suggest that the reduction in HE recurrence was demonstrated regardless of FMT dose, donor, and route of administration,” the investigators said. “Donor engraftment was enhanced by higher relative abundances of Lachnospiraceae in recipients, which were associated with lower HE recurrence rates.”

Burden

HE patients on lactulose and rifaximin remain underserved and carry a large medical, psychosocial, and financial burden. Since they are not usually prioritized for liver transplantation, interventions that reduce their risk of recurrence are important.

“Our experience, which is the largest cohort of such patients to date, showing safety of FMT products regardless of route or dose is encouraging,” the researchers said. [Hepatology 2019;70:1690-1703; Hepatology 2017;66:1727-1738; Hepatol Commun 2022;6:2079-2089]

“These results are … important because enemas are poorly accepted, and several doses at one or two sittings may be sufficient to reduce HE recurrence risk. The longer-term results mirror a prior experience with enema FMT in a similar population,” they added. [Gastroenterology 2019;156:1921-1923]

Protection

The protective effect of FMT against HE shown in the current study emphasizes the role played by the gut microbiota in HE pathogenesis.

“A more intensive FMT regimen is likely needed to impact non-HE complications of cirrhosis like spontaneous bacterial peritonitis, which may be driven by gut pathogens with higher abundance of virulence and antibiotic resistance genes,” the researchers said. [Gut Microbes 2021;13:1993584]

“Further studies are needed to expand the results across a larger population of patients with cirrhosis,” they added.