Efficacy of rifaximin against covert hepatic encephalopathy and hyperammonemia in Japanese patients

Abstract

Covert hepatic encephalopathy (CHE) impairs patient quality of life and occurs in approximately 30% of liver cirrhosis (LC) cases. Japanese clinical practice guidelines recommend rifaximin to treat overt HE (OHE). However, the usefulness of rifaximin against CHE is not thoroughly investigated in Japanese patients. We aimed to investigate the efficacy of rifaximin against hyperammonemia and CHE in Japan. We observed 102 patients with HE showing hyperammonemia secondary to LC and examined various biochemical and behavioral parameters following rifaximin treatment. CHE was diagnosed when the patients exhibited two or more abnormal neuropsychological test (NPT) scores but did not indicate OHE symptoms. In the 102 cases, a significant therapeutic effect of rifaximin on hyperammonemia was observed from 2 to 48 weeks after starting treatment. Excluding 10 patients diagnosed with OHE upon starting rifaximin treatment, 12 of the 92 remaining patients (11.8%) transitioned to OHE within 1 year. The 1 year cumulative OHE transition rate was 14.5%. Among the 24 patients with CHE diagnosed by the NPT for whom NPT results could be evaluated at 4 and 12 weeks after starting treatment, 10 (41.6%) had recovered from CHE at 12 weeks. When the factors contributing to recovery from CHE were examined by multivariate analysis, an ammonia level <129 μg/dL was a significant factor. Rifaximin was thus significantly effective against both hyperammonemia and CHE in Japanese patients.

Fig 1. Patient flow chart.

Flowchart indicating patient classification. NPT, neuropsychological tests; OHE, overt hepatic encephalopathy; CHE, covert hepatic encephalopathy.

Fig 2. Effect of rifaximin treatment on hyperammonemia.

(a) Changes in the blood ammonia levels in patients from pre-treatment to 48 weeks after starting treatment are shown on the Y-axis. (b) Changes in the relative ratio of the ammonia level measured during treatment to its pre-treatment value are shown on the Y-axis. In each graph, plots and data represent the mean ± standard deviation (SD).

Fig 3. One-year cumulative transition rate to overt hepatic encephalopathy (OHE).

Fig 4. Effect of rifaximin in improving covert hepatic encephalopathy (CHE).

(a) Total abnormal scores of neuropsychological tests (NPT) are shown on the Y-axis. Plots and data represent the mean ± SD. (b) Number of patients with CHE before and 12 weeks after treatment is shown on the Y-axis.

Fig 5. Ammonia levels before treatment with rifaximin and after recovery from covert hepatic encephalopathy (CHE).

(a) Receiver operating characteristic curve showing the baseline ammonia level that is predictive of recovery from CHE at 12 weeks after rifaximin administration. (b) The Y-axis presents the percentage of cases showing recovery from CHE when cases were categorized according to the ammonia level (NH₃ < 129 μg/dL and NH₃ ≥ 129 μg/dL).