Long-term management of hepatic encephalopathy with lactulose and/or rifaximin: a review of the evidence

Abstract

A consolidated overview of evidence for the effectiveness and safety/tolerability of hepatic encephalopathy (HE) treatment over the long term is currently lacking. We identified and assessed published evidence for the long-term (≥6 months) pharmacological management of HE with lactulose and/or rifaximin. A literature search was conducted in PubMed (cutoff date 05 March 2018) using the search terms 'hepatic encephalopathy+rifaximin' and 'hepatic encephalopathy+lactulose'. All articles containing primary clinical data were manually assessed to identify studies in which long-term (≥6 months) effectiveness and/or safety/tolerability end points were reported for lactulose and/or rifaximin. Long-term effectiveness outcomes were reported in eight articles for treatment with lactulose alone and 19 articles for treatment with rifaximin, alone or in combination with lactulose. Long-term safety/tolerability outcomes were reported in six articles for treatment with lactulose alone and nine articles for treatment with rifaximin, alone or in combination with lactulose. These studies showed that lactulose is effective for the prevention of overt HE recurrence over the long term and that the addition of rifaximin to lactulose significantly reduces the risk of overt HE recurrence and HE-related hospitalization, compared with lactulose therapy alone, without compromising tolerability. Current evidence therefore supports recommendations for the use of lactulose therapy for the prevention of overt HE recurrence over the long term, and for the additional benefit of adding rifaximin to lactulose therapy. Addition of rifaximin to standard lactulose therapy may result in substantial reductions in healthcare resource utilization over the long term, by reducing overt HE recurrence and associated rehospitalization.

Fig. 1

Summary of numbers of journal articles indexed on PubMed, identified using the search terms ‘hepatic encephalopathy+lactulose’ and ‘hepatic encephalopathy+rifaximin’. Searches were conducted of titles and abstracts only, with language restricted to English and the date range unrestricted up to the cutoff date (5 March 2018). ^aArticles without an abstract; ^barticles containing primary clinical trial, clinical practice study, observational, registry, health economic, or survey data, including journal-published congress abstracts, if indexed on PubMed; ^c≥6 months; ^darticles relating to rifaximin alone or in combination with lactulose; ^earticles relating to lactulose alone.

Fig. 2

NNTs with 95% CIs for lactulose versus no lactulose/placebo ,, rifaximin+lactulose versus placebo+lactulose ,, and rifaximin monotherapy versus rifaximin+lactulose . CI, confidence interval; NNT, number needed to treat.