Efficacy of rifaximin, a poorly absorbed rifamycin antimicrobial agent, for hepatic encephalopathy in Japanese patients

Abstract

Aim Rifaximin is recommended as treatment for hepatic encephalopathy (HE) that targets intestinal bacterial flora. Although combined use with synthetic disaccharides is the standard of care worldwide, the therapeutic effects of rifaximin for overt encephalopathy (OHE) in Japanese patients have not been examined sufficiently. We examined the therapeutic effects of rifaximin for OHE in Japanese patients. Methods A total of 76 patients who developed OHE of West Haven grade II or higher at least once within the 12 months before starting rifaximin were included. Blood ammonia levels and the incidence of OHE during the 12 months before and after starting rifaximin therapy were compared in a before‐and‐after study. Rifaximin efficacy and predictors of efficacy were also examined. Results Post‐treatment blood ammonia levels were significantly lower than pretreatment levels. The mean annual number of OHE incidents and intravenous branched‐chain amino acid preparations used per patient were significantly lower after starting rifaximin therapy (2.51 vs. 0.76 times/year, p < 0.001; and 71.9 vs. 20.7 preparations/year, p = 0.003, respectively). The cumulative incidence of hospitalizations associated with HE significantly decreased after rifaximin therapy (hazard ratio 0.187; p < 0.001). The efficacy rate, defined as the proportion of patients without OHE during the administration of rifaximin for 1 year after starting rifaximin therapy, was 65.8%. Serum albumin ≥2.7 g/dl was an independent predictor of efficacy. Conclusion Rifaximin was associated with decreased blood ammonia levels, lower incidence of OHE, and fewer hospitalizations in Japanese patients with HE. In addition, serum albumin level was an important predictor on efficacy of rifaximin.

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

“…Rifaximin (Rifxima ® ; ASKA Pharmaceutical, Tokyo, Japan) was approved for the HE treatment in November 2016 in Japan. However, only data from clinical trials were available up to 12 weeks of administration [ 12 ], and data on the long-term efficacy and safety of rifaximin treatment have been limited in Japan [ 13 , 14 , 15 , 16 ]. Moreover, all data were obtained from a single-center retrospective study.…”

Role of serum albumin in hepatic encephalopathy

“…prevented the recurrence of HE and decreased the cumulative incidence of hospitalization associated with HE in Japanese patients. 2 They also reported that serum albumin level was an independent predictor of the efficacy of rifaximin, and a serum albumin level of 2.7 g/dl was considered the optimal cut-off for efficacy. Furthermore, they reported that the incidence of overt HE and the number of hospitalizations were significantly lower in patients with serum albumin levels ≥2.7 g/dl than in those with serum albumin levels <2.7 g/dl.…”

“…6 In addition, only a few reports have evaluated the efficacy of rifaximin treatment in Japan. 2,[7][8][9] Recently, the long-term use of rifaximin has been reported to be safe and effective for HE in Japanese patients. 7 Hiramine et al also showed that 12 months of rifaximin treatment reduced ammonia levels and overt HE incidence and the number of hospitalizations.…”

“…7 Hiramine et al also showed that 12 months of rifaximin treatment reduced ammonia levels and overt HE incidence and the number of hospitalizations. 2 Albumin is a multifunctional protein whose concentration and function are reduced in advanced liver failure. 10 Decreased serum albumin levels might be associated with the development of HE.…”

“…No significant difference was found between patients who received albumin and those who did not, due to the small number of cases; however, patients who received albumin tended to have a better response to rifaximin and lower average incidence of overt HE than those who did not receive albumin. 2 Current guidelines suggest that the timing of albumin infusion should be at serum albumin level of <2.5 g/dl. 19 However, it should be commenced earlier in cirrhotic patients with hypovolemia and refractory ascites, even for patients with a serum albumin level of >2.5 g/dl.…”