Efficacy and Safety of Rifaximin Versus Placebo or Other Active Drugs in Critical ill Patients With Hepatic Encephalopathy.

Xianghui Han,Peiyong Zheng,Tian Li,Wenyi Wang,Zubing Mei,Jianyi Wang,Zhanyang Luo

doi:10.3389/fphar.2021.696065

Abstract

Objective: Rifaximin has been approved for use as a first-line therapy for secondary prophylaxis of hepatic encephalopathy (HE). This article is to update existing evidence on efficacy and safety of rifaximin treatment and prevention for HE. Methods: We systematically searched multiple databases until January 31 2021. The studies compared rifaximin vs. placebo or other active drugs (i.e., nonabsorbable disaccharides, other antibiotics, L-ornithine-L-aspartate (LOLA), and probiotics) for patients with overt HE (OHE), minimal HE (MHE), and recurrent HE. Results: Twenty-eight randomized controlled trials with a total of 2979 patients were included. Compared with the controls, rifaximin significantly reduced HE grade (OHE: RR = 1.11, 95% CI = 1.02–1.21), improved the cognitive impairments (MHE: RR = 1.82, 95% CI = 1.12–2.93) and prevented the risk of HE recurrent episodes (RR = 1.33, 95% CI = 1.18–1.49). No statistical difference was observed in mortality between rifaximin and their controls (RR = 0.82, 95% CI = 0.54–1.24). The incidence of total adverse events in rifaximin-treated groups was significantly lower than that in the controls during the treatment period (RR = 0.73, 95% CI = 0.54–0.98). In addition, rifaximin treatment was better than other active drugs in improving psychometric indicators (mental state, flapping tremor and portosystemic encephalopathy (PSE) index) and reducing the risk of rehospitalization in HE patients. Conclusion: Rifaximin therapy is effective and well-tolerated in different types of HE, which might be recommended as an alternative to conventional oral drugs in clinical settings.

Highlights

Hepatic encephalopathy (HE) is a frequent and serious complication of end-stage liver cirrhosis due to liver insufficiency or portosystemic shunting (American Association for the Study of Liver, 2014)
The overall results showed that rifaximin was superior to other active drugs in decreasing HE grade of patients with acute or chronic Overt HE (OHE) (RR 1.11, 95% confidence interval (CI) 1.02–1.21, p 0.022)
Further subgroup analysis indicated that rifaximin treatment was better than nonabsorbable disaccharides in terms of OHE improvement (RR 1.13; 95% CI 1.02–1.26, p 0.017), whereas there was no difference between rifaximin and other antibiotics (RR 1.05, 95% CI 0.89–1.22, p 0.575), Figure 4A

Summary

Introduction

Hepatic encephalopathy (HE) is a frequent and serious complication of end-stage liver cirrhosis due to liver insufficiency or portosystemic shunting (American Association for the Study of Liver, 2014). According to the severity of manifestations, HE is subdivided into minimal and overt (grade I–IV) types by the West Haven Criteria (Ferenci, 2017). Overt HE (OHE) presents abnormal blood ammonia levels and neurological symptoms including asterixis, deterioration of mental state, and even coma, which leads to a burden on health care systems and a notable decline in quality of life (Weissenborn et al, 2005). Minimal HE (MHE) mainly encompasses cognitive impairment, such as attention, alertness, orientation, and learning processes, which is detected through changes in neuro-psychometric (NP) or critical flicker frequency (CFF) tests. It is reported that OHE occur in 30–40% of patients with liver cirrhosis and MHE occurred in 20–80% of those with cirrhosis during their clinical course (Romero-Gómez et al, 2007). HE recurrence can aggravate clinical symptoms and increase rehospitalization and mortality (Tapper et al, 2016; Wang et al, 2021)

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Discussion

Conclusion