Combination of rifaximin and lactulose improves clinical efficacy and mortality in patients with hepatic encephalopathy

Abstract

BackgroundRifaximin and lactulose are common effective agents for hepatic encephalopathy (HE). Whether a combination of rifaximin and lactulose improves the efficacy and mortality in patients with HE compared with lactulose alone needs to be analyzed.MethodsA systematic search was performed in electronic databases and other sources for possible studies focusing on combination therapy of rifaximin and lactulose for HE between January 2000 and February 2018. A meta-analysis was performed by the method recommended by the Cochrane Collaboration, and estimated effect size was presented as risk difference (RD), 95% CI, and the number needed to treat (NNT). Subgroup analysis, sensitivity analysis, and Trial Sequence Analysis were comprehensively performed to indicate the source of heterogeneity and risk of bias.ResultsFive randomized and five observational studies involving 2,276 patients were included. Combination therapy had a significant advantage in both clinical efficacy increase (RD 0.26, 95% CI 0.19–0.32, NNT 5) and mortality decrease (RD −0.16, 95% CI −0.20–0.11, NNT 9) in overall analysis. In the pooled analysis of randomized studies, combination therapy showed similar results in clinical efficacy (RD 0.25, 95% CI 0.16–0.35, NNT 4) and mortality (RD −0.22, 95% CI −0.33–0.12, NNT 5). Compared with lactulose, hospital stay was also reduced in combination therapy, and there was no significant difference in treatment-related adverse events between the two groups.ConclusionCombination of rifaximin and lactulose has beneficial effects on HE. Compared with lactulose alone, additional rifaximin increases clinical efficacy and decreases mortality. However, its effects on different types of HE are still uncertain.

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

“…In the present study, rifaximin was associated with lower blood ammonia levels, fewer incidents of OHE, and a much lower number of hospitalizations in patients with relatively advanced disease and a history of grade II HE or higher. The absence of changes in multiple factors, such as hepatic or renal function, doses of oral drugs used concomitantly with rifaximin, ratio of blood urine nitrogen/creatinine ratio, and dose of diuretic and so on before and after rifaximin therapy suggests that rifaximin is effective in preventing OHE in Japanese patients, as reported previously 3 4 , 9 , 17 – 20 The reduction in the volume of intravenous BCAA preparations used to treat coma associated with OHE was observed in the present study, and the decrease in the number of outpatient visits per patient (data not shown) after the launch of the Rifxima® tablet at our hospital suggests that rifaximin has a therapeutic effect, which improves the quality of life in patients with OHE.…”

Budget impact of optimizing rifaximin-α use for the prevention of recurrent hepatic encephalopathy in The Netherlands

“…Therefore, the mortality rates were calculated based on a Korean study in 1,042 patients experiencing HE 13 , which may not entirely represent the Dutch HE population as there could be between-country differences in the patient population, disease course, and healthcare provided. On the other hand, the major advantage of this Korean study is that it specifically assessed the effect of rifaximin-a (with lactulose) versus lactulose monotherapy in a real-world setting with a long-term follow-up of 48 months in a relatively high number of patients compared to other studies or clinical trials 39 , making it the most suitable study to use for our analysis.…”

Thrombospondin-1 Exacerbates Acute Liver Failure and Hepatic Encephalopathy Pathology in Mice by Activating Transforming Growth Factor β1

“…47e50 Clinical treatments for HE that commonly are used are lactulose and rifaximin, which reduce ammonia levels and have been shown to improve outcomes. 51,52 That being said, these treatments have differing degrees of therapeutic efficacy depending on the metric assessed. Therefore, the need to develop new therapies, or therapies to use in conjunction with current treatments, for management of this syndrome is critically important.…”