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. 2022 Mar 12;11(6):1571.
doi: 10.3390/jcm11061571.

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

Hideto Kawaratani  1 , Yasuteru Kondo  2 , Ryoji Tatsumi  3 , Naoto Kawabe  4 , Norikazu Tanabe  5 , Akira Sakamaki  6 , Kazuo Okumoto  7 , Yoshihito Uchida  8 , Kei Endo  9 , Takumi Kawaguchi  10 , Tsunekazu Oikawa  11 , Yoji Ishizu  12 , Shuhei Hige  3 , Taro Takami  5 , Shuji Terai  6 , Yoshiyuki Ueno  7 , Satoshi Mochida  8 , Yasuhiro Takikawa  9 , Takuji Torimura  10 , Tomokazu Matsuura  11 , Masatoshi Ishigami  12 , Kazuhiko Koike  13 , Hitoshi Yoshiji  1
Affiliations

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

Hideto Kawaratani et al. J Clin Med. .

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.

Keywords: Japanese; cirrhosis; hepatic encephalopathy; long-term; rifaximin.

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Conflict of interest statement

Satoshi Mochida, Shuji Terai, Yoshiyuki Ueno, Kazuhiko Koike, and Hitoshi Yoshiji received lecture fees provided by ASKA Pharmaceutical Co., Ltd. Satoshi Mochida, Shuji Terai, Yoshiyuki Ueno, and Kazuhiko Koike received research funding from ASKA Pharmaceutical Co., Ltd. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Changes in serum ammonia levels after rifaximin administration. (A) The ammonia levels significantly improved following rifaximin therapy from 102.9 ± 59.0 μg/dL to 79.7 ± 46.3 μg/dL, 80.1 ± 45.3 μg/dL, and 79.3 ± 44.1 μg/dL after 3, 6, and 12 months, respectively. (B) The ammonia levels of patients with Child–Pugh C significantly improved following rifaximin therapy from 109.7 ± 61.9 μg/dL to 84.5 ± 48.6 μg/dL, 86.5 ± 45.4 μg/dL, and 86.9 ± 39.5 μg/dL after 3, 6, and 12 months, respectively. A statistically significant difference was observed between the values at baseline and at 3, 6, 12 months. NH3, ammonia; Pre, before rifaximin treatment; 3M, after 3 months of rifaximin treatment; 6M, after 6 months of rifaximin treatment; 12M, after 12 months of rifaximin treatment. * p < 0.05, *** p < 0.001.
Figure 2
Figure 2
Cumulative incidence of the occurrence of hepatic encephalopathy. Pre, before rifaximin treatment; 3M, after 3 months of rifaximin treatment; 6M, after 6 months of rifaximin treatment; 9M, after 9 months of rifaximin treatment; 12M, after 12 months of rifaximin treatment.
Figure 3
Figure 3
Effects of rifaximin on renal function and electrolytes in 215 patients with hepatic encephalopathy. (A) BUN; (B) Cr; (C) eGFR; (D) Na; (E) K. BUN, Cr, eGFR, Na, and K did not differ after rifaximin administration. BUN, blood urea nitrogen; Cr, creatinine; eGFR, estimated glomerular filtration rate; Na, sodium; K, potassium; Pre, before rifaximin treatment; 3M, after 3 months of rifaximin treatment; 6M, after 6 months of rifaximin treatment; 12M, after 12 months of rifaximin treatment.
Figure 4
Figure 4
Effects of rifaximin on the hepatic reserve in 215 patients with hepatic encephalopathy. (A) T−bil; (B) PT activity; (C) Alb; (D) ALBI score; (E) MELD score. The PT activity, Alb level, and ALBI score improved after rifaximin administration. T−bil, total bilirubin; PT, prothrombin; Alb, albumin; ALBI, albumin−bilirubin; MELD, model for end−stage liver disease; Pre, before rifaximin treatment; 3M, after 3 months of rifaximin treatment; 6M, after 6 months of rifaximin treatment; 12M, after 12 months of rifaximin treatment. * p < 0.05 compared with before rifaximin treatment, ** p < 0.01 compared with before rifaximin treatment, *** p < 0.001 compared with before rifaximin treatment.
Figure 5
Figure 5
Effects of rifaximin on the hepatic reserve in 27 patients with hepatic encephalopathy limited to Child−Pugh C. (A) PT activity; (B) Alb; (C) ALBI score; (D) MELD score. The PT activity, Alb level, and ALBI score improved after 3 months of rifaximin administration. PT, prothrombin; Alb, albumin; ALBI, albumin–bilirubin; MELD, model for end−stage liver disease; Pre, before rifaximin treatment; 3M, after 3 months of rifaximin treatment; 6M, after 6 months of rifaximin treatment; 12M, after 12 months of rifaximin treatment. * p < 0.05 compared with before rifaximin treatment.
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