Microbiota transplantation in patients with cirrhosis and hepatic encephalopathy
Bajaj JS et al, J Hepatol. 2025;83(1):81-91
The results of a US study with 60 patients show that microbiome transfer can prevent recurrences of hepatic encephalopathy episodes and thereby improve cognitive outcomes and quality of life without relevant side effects. The potential clinical applicability is underscored by the observation that recurrence rates were comparable regardless of route of administration, dosage, or donor type.
Background and aims: Preventing hepatic encephalopathy (HE) recurrence in cirrhosis, which is associated with an altered gut-liver-brain axis, is an unmet need. Benefits of fecal microbiota transplantation (FMT) have been shown in phase I studies, but route and dose-related questions remain.
Methods: The authors performed a phase II randomized, placebo-controlled, double-blind, clinical trial of capsule and enema FMT in patients with cirrhosis and HE on lactulose and rifaximin. Participants were randomized into four groups (3 active doses; 2 active and 1 placebo dose; 1 active and 2 placebo doses; 3 placebo doses). Each patient received two capsules and one enema (either placebo or FMT) and were followed for 6 months. The primary outcome was FMT-related (serious) adverse events ([S]AEs)/AEs using intention-to-treat analysis. Secondary outcomes were HE recurrence, all-cause hospitalizations, death, donor engraftment, and quality-of-life. FMT was from a vegan or omnivorous donor.
Results: They enrolled 60 patients (15/group) with similar baseline characteristics. FMT was safe, with no FMT-related SAEs/AEs reported. Overall SAEs (p = 0.96) or death (p = 1.0) were similar. There were significant differences in HE recurrence between groups (p = 0.035, Cramer's V = 0.39). On post hoc analysis, recurrence was highest in the all-placebo versus any FMT group (40% vs. 9%; odds ratio = 0.15, 95% CI: 0.04–-0.64). Within the FMT groups, HE recurrence rates were similar regardless of route, doses, or donor type. Quality of life improved in FMT-recipient groups. Engraftment was highest in those with high pre-FMT Lachnospiraceae and lower in those whose HE recurred.
Conclusions: Fecal microbiota transplantation (FMT) was safe in patients with cirrhosis and hepatic encephalopathy (HE) on maximal therapy, with no FMT-related advers events reported, regardless of dose, route, or donor type. On post hoc analysis, HE recurrence was highest in the placebo-only group and linked with lower baseline Lachnospiraceae and reduced donor engraftment.