Clinical efficacy and safety of lactulose for minimal hepatic encephalopathy: a meta-analysis.

OBJECTIVE: To evaluate the clinical efficacy of lactulose in patients with minimal hepatic encephalopathy (MHE).

METHODS: Randomized controlled trials (RCTs) comparing lactulose with placebo or with no intervention in the management of MHE that were conducted from January 1990 to July 2011 were searched from MEDLINE, EMBASE, SCI, Cochrane Controlled Trials Register, and China Biological Medicine Database. Studies with a Jadad score higher than 3 were included in the meta-analysis and evaluated using RevMan5.0 software for relative risk (RR) or weighted mean difference (WMD) with 95% confidence intervals (95% CI). Sensitivity analysis was performed on the ethnical differences and quality of the trials. Publication bias was observed using an inverted funnel plot.

RESULTS: Nine studies with 434 patients were included in the meta-analysis. Compared with placebo or no intervention, lactulose significantly reduced the risk of no improvement in neuropsychological tests (RR: 0.52, 95% CI: 0.44-0.62, P<0.00001), the time required for the completion of the number connection test-A (WMD: -26.95, 95% CI: -37.81 to -16.10, P<0.00001), and the mean number of abnormal neuropsychological tests (WMD: -1.76, 95% CI: -1.96 to -1.56, P<0.00001). Furthermore, the meta-analysis also showed that lactulose prevented the progression to overt hepatic encephalopathy (RR: 0.17, 95% CI: 0.06-0.52, P=0.002), reduced blood ammonia levels (WMD: -9.89 µmol/l, 95% CI: -11.01 to -8.77 µmol/l, P<0.00001), and improve health-related quality of life (WMD: -6.05, 95% CI: -6.30 to -5.20, P<0.00001). However, no significant difference was observed in the mortality of patients with MHE (RR: 0.75, 95% CI: 0.21-2.72, P=0.66), and lactulose significantly increased the incidence of diarrhea (RR: 4.38, 95% CI: 1.35-14.25, P=0.01).

CONCLUSION: Lactulose has significant beneficial effects for patients with MHE compared with placebo or no intervention.