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

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.

Figure 1.. Proposed conceptual framework of HRQOL in hepatic encephalopathy

Figure 2.. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram of studies included in systematic review

Figure 3.. Pooled mean difference in total Sickness Index Profile (SIP) scores among patients treated with lactulose

Figure 4.. Percentage change in patient reported outcomes among patients with HE treated with lactulose and/or rifaximin for

(A) overall health-related quality of life, (B) sleep, (C) physical activity, and (D) social activity Percentage change based on total range of scores for each individual patient reported outcome instrument. Adjacent bars come from same study and positive values denote improvement in patient-reported outcomes. SIP: Sickness Index Profile; CLDQ: Chronic Liver Disease Questionnaire; CQoLQ: Modified Chinese QoL Questionnaire; ESS: Epworth Sleepiness Scale; PSQI: Pittsburgh Sleep Quality Index; WHOQOL-BREF: World Health Organization Quality of Life-BREF; SF-36: 36-Item Short Form Survey; SF-8: 8-Item Short Form Survey; * Intragroup difference (i.e. before vs after) significant at p<0.05; † Intergroup difference (i.e. treatment vs comparator) significant at p<0.05; ^ Short-term (8 weeks) lactulose; ‡ Long-term (24 weeks) lactulose; Statistical significance not reported for CLDQ (Sanyal et al.)