Long-Term Efficacy and Safety of Rifaximin in Japanese Patients with Hepatic Encephalopathy: A Multicenter Retrospective Study

Abstract

Background: Rifaximin is commonly used for hepatic encephalopathy (HE). However, the effects of long-term treatment for Japanese people are limited. Therefore, this study aimed to investigate the effects and safety of long-term treatment with rifaximin on HE. Methods: A total of 215 patients with cirrhosis administered with rifaximin developed overt or covert HE, which was diagnosed by an attending physician for >12 months. Laboratory data were extracted at pretreatment and 3, 6, and 12 months after rifaximin administration. The long-term effect of rifaximin was evaluated, and the incidence of overt HE during 12 months and adverse events was extracted. Results: Ammonia levels were significantly improved after 3 months of rifaximin administration and were continued until 12 months. There were no serious adverse events after rifaximin administration. The number of overt HE incidents was 9, 14, and 27 patients within 3, 6, and 12 months, respectively. Liver enzymes, renal function, and electrolytes did not change after rifaximin administration. Prothrombin activity is a significant risk factor for the occurrence of overt HE. The serum albumin, prothrombin activity, and albumin–bilirubin (ALBI) scores were statistically improved after 3 and 6 months of rifaximin administration. Moreover, the same results were obtained in patients with Child–Pugh C. Conclusions: The long-term rifaximin treatment was effective and safe for patients with HE, including Child–Pugh C.

Rifaximin stimulates nitrogen detoxification by PXR‐independent mechanisms in human small intestinal organoids

“…However, non‐response in terms of ammonia decrease in these studies could be because of small sample size or the big spread in measurement outcomes owing to the difficulties in measurement of the volatile ammonia metabolite. Importantly, even long‐term studies and studies where rifaximin was used as add‐on to lactulose showed blood ammonia reduction by rifaximin (from 60 μmol/L to 47 μmol/L after 12 months and −40 μmol/L as add‐on respectively) 16,17 …”

“…Therefore, the question remains whether the effects of rifaximin on the microbiota composition and ammonia concentration are mediated by direct effects on the microbiome or direct effects on the intestinal epithelium (leading to increased barrier function) or both. The capacity of rifaximin to lower blood ammonia levels was confirmed in a meta‐analysis of 12 trials and long‐term real‐world data studies 15–17 . We therefore hypothesized that rifaximin, next to its effects as an intestinal antibiotic also directly impacts the small intestinal epithelial biotransformation machinery by stimulating nitrogen detoxification.…”

“…The capacity of rifaximin to lower blood ammonia levels was confirmed in a meta-analysis of 12 trials and long-term real-world data studies. [15][16][17] We therefore hypothesized that rifaximin, next to its effects as an intestinal antibiotic also directly impacts the small intestinal epithelial biotransformation machinery by stimulating nitrogen detoxification.…”

“…Importantly, even long-term studies and studies where rifaximin was used as add-on to lactulose showed blood ammonia reduction by rifaximin (from 60 μmol/L to 47 μmol/L after 12 months and −40 μmol/L as add-on respectively). 16,17 Treatment of HE mainly focused on the liver and colon in the past, when rectal rather than oral lactulose was provided. Results from our study imply that rifaximin has beneficial effects on the gut epithelium of the small intestine.…”

Add-on Therapeutic Effects of Rifaximin on Treatment-resistant Hepatic Encephalopathy

“…Rifaximin inhibits ammonia-producing bacteria in the gut (17)(18)(19), lowers blood ammonia, and prevents hepatic encephalopathy (20)(21)(22). It is widely used in Europe and the United States in the treatment of hepatic encephalopathy.…”