Efficacy of long-term rifaximin treatment for hepatic encephalopathy in the Japanese

Abstract

Background: Hepatic encephalopathy (HE) is a complication of liver cirrhosis and can result in neuropsychological and neuromuscular dysfunctions in patients. Rifaximin, an antibiotic, has been reported to decrease the occurrence of overt HE and also improve cognitive function in studies from Europe and the United States of America. There is not enough evidence of the relationship between the long-term use of rifaximin and its clinical effects in the Japanese.

Aim: To determine the clinical effects of long-term rifaximin therapy in decompensated liver cirrhosis patients, with overt HE or hyperammonemia.

Methods: In this single-center retrospective observational cohort study, we reviewed the data of 38 patients who had taken rifaximin at the dose of 1200 mg/d for more than 24 wk. The primary outcome measured was the efficacy of long-term rifaximin use, and secondary outcome measured was the safety of its long-term use as determined by its influence on portosystemic shunts as well as Escherichia coli-related infections. Moreover, we compared the prognosis between the rifaximin group and control cases, matched for hepatic elasticity assessed by magnetic resonance ela-stography, age, and Child-Pugh classification.

Results: Of the 38 patients included in the study, 12 (31.6%) had overt HE, 27 (71.1%) had complications of esophageal varices, and 9 (23.7%) had hepatocellular carcinoma (HCC). The control group was matched for age, Child-Pugh classification, liver stiffness, and presence of HCC. The median of serum ammonia level before treatment was 104 μg/dL (59-297), and 2 wk after treatment, it significantly decreased to 85 μg/dL (34-153) (P = 0.002). A significantly low value of 80.5 μg/dL (44-150) was maintained 24 wk after treatment. The long-term use of rifaximin did not cause a decline in liver function. Diarrhea occurred in 2 patients, who improved with the administration of probiotics, and there were no cases of aborted rifaximin therapy owing to adverse events. In patients with Child C, the survival was short, but there was no significant difference compared with that of the control group.

Conclusion: Rifaximin therapy improves overt HE. The long-term use of rifaximin in the Japanese is effective and safe.

Keywords: Child-Pugh classification; Hepatic cirrhosis; Hepatic encephalopathy; Magnetic resonance elastography; Rifaximin; Spontaneous portosystemic shunt.

Figure 1

Serum ammonia levels. Before rifaximin treatment, median of blood ammonia level was 104 μg/dL (range, 59-297 μg/dL), whereas two weeks after the treatment it decreased to 85 μg/dL (34-153), showing a significant difference (P = 0.002). The median values were 71 μg/ dL (47-341) after 4 wk, 79.5 μg/ dL (37-215) after 8 wk, 70 μg/ dL (31-221) after 12 wk, 80.5 μg/dL (44-150) after 24 wk, 81 μg/dL (20-298) after 36 wk, 91 μg/dL (53-169) after 48 wk, and eventually 85 μg/dL (45-192) after 60 wk. Decrease was noted at all the points after the start of the treatment when compared with the ones before it.

Figure 2

Kaplan-Meir survival curves. A: Results from log-rank test showed significant differences in Child-Pugh A and B vs Child-Pugh C. a: Survival data of patients with Child-Pugh A and B (n = 30), b: Survival data of patients with Child-Pugh C (n = 8). Median survival time was 43 wk; B: Results from log-rank test showed no significant differences of rifaximin group vs control group. a: Survival data of rifaximin group (n = 38), b: Survival data of control group (n = 34).