Rapid ammonia normalization and long-term efficacy of rifaximin in patients with cirrhosis: a multicenter retrospective study.

OBJECTIVE: Hyperammonemia drives the pathogenesis of hepatic encephalopathy and independently predicts poor outcomes in cirrhosis. Despite the widespread use of rifaximin, data on ammonia normalization kinetics and long-term effects on hepatic functional reserve remain limited. We aimed to evaluate the efficacy and safety of long-term rifaximin therapy for hyperammonemia in patients with cirrhosis. METHODS: This multicenter retrospective study analyzed 247 cirrhotic patients with hyperammonemia treated with rifaximin at six institutions in Japan (2016-2022). Ammonia normalization kinetics and predictors, hepatic functional reserve, and safety were assessed over a median follow-up of 377 days. RESULTS: Blood ammonia concentrations (BACs) decreased by 34.7% at 1 week, and 74.5% of patients achieved normalization at a median of 63 days. Lower serum albumin was independently associated with delayed normalization. Serum albumin, prothrombin time, and the Child-Pugh score showed small but statistically significant improvements at 12 months, whereas the MELD and ALBI scores remained stable. Hepatic encephalopathy-related hospitalizations decreased by 60.2% compared with the preceding 2 years. Adverse events occurred in 2.0% of patients, all grade 1. CONCLUSION: Rifaximin rapidly normalized BACs, and this effect was sustained during long-term therapy. Long-term rifaximin administration was associated with a mild improvement in some indicators of hepatic functional reserve, suggesting that it may contribute to the maintenance or improvement of hepatic functional reserve. Lower baseline albumin is associated with delayed normalization, highlighting the importance of hepatic functional reserve in treatment response.