Lactulose and rifaximin combination therapy as first-line treatment for preventing recurrent overt hepatic encephalopathy: a retrospective observational study

BACKGROUND AND AIM: Lactulose and rifaximin are recommended therapies for hepatic encephalopathy. Although the usefulness of the combination is evident, there is a paucity of real-world data regarding the efficacy of lactulose and rifaximin combination therapy when used immediately after overt hepatic encephalopathy (OHE) onset. This study aimed to clarify the prophylactic effect of using combination therapy as a first-line treatment in real-world clinical practice. METHODS: In this retrospective cohort study, 96 patients who had developed OHE and subsequently improved were included. As first-line prophylactic therapy, 37 patients received lactulose and rifaximin combination therapy, while 59 patients received lactulose monotherapy. The primary outcome was OHE recurrence within 12 months. RESULTS: The cohort represented a real-world Japanese population of elderly patients with advanced cirrhosis. The 12-month cumulative incidence rates of OHE recurrence were significantly lower in the combination therapy group (25.0%) compared with the monotherapy group (49.3%) (Gray's test P = 0.026). In the Fine-Gray multivariable analysis, combination therapy significantly reduced recurrence risk, with a subdistribution hazard ratio of 0.44 (95% confidence interval: 0.20-0.97). CONCLUSION: Lactulose and rifaximin combination therapy significantly suppressed OHE recurrence more effectively than lactulose monotherapy when used as a first-line treatment. Our findings suggest clarify the prophylactic benefit of the two-drug combination; this therapy may be a more useful first-line treatment for patients with OHE and could be recommended.