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

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.

Real-world evidence of long-term survival and healthcare resource use in patients with hepatic encephalopathy receiving rifaximin-α treatment: a retrospective observational extension study with long-term follow-up (IMPRESS II)

“…It is unclear whether RFX directly improves survival in patients with HE, with conflicting results reported in two independent meta-analyses when compared with active treatments or placebo 14 23. Other studies have suggested that RFX treatment may improve survival, but this remains to be substantiated by larger RCTs 24–27…”

“…The efficacy and safety of RFX was evaluated in a meta-analysis of 28 randomised controlled trials (RCTs) of RFX versus other active drugs or placebo for patients with HE. In that analysis, RFX was shown to significantly reduce HE grade, improve cognitive impairment and reduce recurrent episodes but no significant improvement in mortality was observed 14. Follow-up lengths for the included RCTs ranged from 3 days to 6 months, leaving the long-term effect of RFX treatment on survival unclear 14…”

“…In that analysis, RFX was shown to significantly reduce HE grade, improve cognitive impairment and reduce recurrent episodes but no significant improvement in mortality was observed. 14 Follow-up lengths for the included RCTs ranged from 3 days to 6 months, leaving the longterm effect of RFX treatment on survival unclear. 14 RFX has been shown to reduce healthcare use for patients receiving RFX treatment in multiple studies, 3 15-19 but the relationship between RFX and mortality remains unclear.…”

“…14 Follow-up lengths for the included RCTs ranged from 3 days to 6 months, leaving the longterm effect of RFX treatment on survival unclear. 14 RFX has been shown to reduce healthcare use for patients receiving RFX treatment in multiple studies, 3 15-19 but the relationship between RFX and mortality remains unclear. There is currently a lack of real-world data on the long-term survival of patients with HE receiving RFX in routine clinical settings.…”

Up-to-date diagnostic and treatment approaches to minimal hepatic encephalopathy in cirrhosis

“…значительно уменьшило когнитивные нарушения у пациентов с MПЭ. Помимо этого, в ходе анализа подгрупп было доказано, что рифаксимин-α превосходит плацебо в достижении регресса МПЭ [47].…”