Systematic Review and Meta-Analysis on the Effects of Lactulose and Rifaximin on Patient-Reported Outcomes in Hepatic Encephalopathy

Am J Gastroenterol. 2023 Feb 1;118(2):284-293. doi: 10.14309/ajg.0000000000002008. Epub 2022 Aug 22.

Abstract

Introduction: Patients with hepatic encephalopathy (HE) suffer from significant symptoms and impaired quality of life. Improved understanding on the potential benefits of first-line HE therapies may aid patient-provider discussions regarding expected benefits of HE treatments. We aimed to perform a systematic review to assess the effects of lactulose and rifaximin on patient-reported outcomes (PROs).

Methods: We searched MEDLINE, EMBASE, and Cochrane Library databases for randomized trials or prospective cohort studies using lactulose and/or rifaximin for the management of HE and assessing changes in PRO using PRO instruments. Physician reviewers independently reviewed titles, abstracts, and full texts and extracted data independently. We performed random-effects meta-analyses to examine the effects of lactulose and rifaximin on PROs.

Results: We identified 16 studies representing 1,376 patients that met inclusion criteria. Most studies assessed treatment of covert HE. In patients with covert HE, lactulose significantly improved overall patient-reported health-related quality of life measured by the Sickness Impact Profile with an estimated pooled mean difference of 6.92 (95% confidence interval: 6.66-7.18) and showed improvements in several subscales. Conversely, rifaximin demonstrated a nonstatistically significant mean difference in the total Sickness Impact Profile of 4.76 (95% confidence interval: -4.23 to 13.76), with strong evidence of heterogeneity between these studies. Studies examining other PRO instruments showed improvements in overall health-related quality of life, social functioning, and sleep from both lactulose and rifaximin.

Discussion: Patients with HE treated with lactulose or rifaximin reported improvements in important PROs. These results may inform provider-patient communication and help manage patient expectations regarding the potential benefits of HE therapies.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Drug Therapy, Combination
  • Gastrointestinal Agents / therapeutic use
  • Hepatic Encephalopathy* / diagnosis
  • Hepatic Encephalopathy* / drug therapy
  • Humans
  • Lactulose / therapeutic use
  • Prospective Studies
  • Quality of Life
  • Rifamycins* / therapeutic use
  • Rifaximin / therapeutic use

Substances

  • Rifaximin
  • Lactulose
  • Gastrointestinal Agents
  • Rifamycins