title: Clinical efficacy and safety of lactulose for minimal hepatic encephalopathy:  a meta-analysis.
abstract: 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).
  
  
  CONCLUSIONS
  Lactulose has significant beneficial effects for patients with MHE compared with placebo or no intervention.
authors.affiliation: Graduate School, Tianjin Medical University, Tianjin Infection Disease Hospital, Tianjin, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Luo
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Chen-Zheng
authors.initials: CZ
authors.lastname: Lu
authors.forename: Wu-Kui
authors.initials: WK
authors.lastname: Cao
mesh_terms: D000328:Adult; D000641:Ammonia / Q000097:blood; D003967:Diarrhea / Q000209:etiology; D018450:Disease Progression; D006501:Hepatic Encephalopathy / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D006801:Humans; D007792:Lactulose / Q000009:adverse effects / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D007792:Lactulose; D000641:Ammonia