Systematic Review and Meta-Analysis of Lactulose for the Prevention and Treatment of Hepatic Encephalopathy.

Hepatic encephalopathy (HE) is morbid and increases mortality in cirrhosis. Lactulose is first-line therapy for HE treatment and secondary prophylaxis; however, data supporting its role in primary prevention of incident HE is less definitive. We therefore conducted a systematic review and meta-analysis of the most current evidence evaluating lactulose for the prevention and treatment of HE to guide future management. Medline, EMBASE, and Cochrane Library databases were searched for randomized controlled trials comparing lactulose to placebo or non-drug control for the treatment or prevention of HE. 17 studies with 1428 patients were analyzed. Random effects meta-analysis evaluated four main outcomes: overt HE (OHE), mortality, treatment discontinuation, and serious adverse events. Bayesian meta-analysis assessed two main outcomes: risk of overt HE and mortality. We found that lactulose significantly reduces the incidence of OHE compared to no lactulose, with a pooled relative risk (RR) of 0.48 (95% CI 0.37-0.63) and RR of 0.43 (95% CI 0.27-0.69) for those focusing on primary prophylaxis. There was no increased risk of adverse events (RR 0.87, 95% CI 0.64-1.17). Further, using Bayesian statistics, there exists a high probability that lactulose reduces mortality in individuals with HE (pooled posterior RR 0.72-0.88). Lactulose therapy safely contributes to a significant reduction in incident HE and is highly likely to reduce mortality. These results should guide HE prevention and management, as well as inform future investigations regarding the long-term benefits of lactulose.