Secondary Prophylaxis of Hepatic Encephalopathy: An Open Label Randomized Controlled Trial of Lactulose Versus Placebo

Abstract

Purpose: Hepatic encephalopathy (HE) is associated with a poor prognosis. Lactulose is used for the treatment of HE. There is no study on the prevention of recurrence of HE using lactulose. Methods: Consecutive cirrhotic patients who recovered from HE were randomized to receive lactulose (HE-L group) or placebo (HE-NL group). All patients were assessed by psychometry [(number connection test (NCT-A and B), figure connection test if illiterate (FCT-A and B), digit symbol test (DST), object assembly test (OAT)], critical flicker frequency test (CFF) and blood ammonia at inclusion. Primary endpoint was development of overt HE. Results: Of 300 patients with HE who recovered, 140(46.6%) met the inclusion criteria and were included. There was high prevalence of abnormal psychometry tests (NCT-A, 67.5%, NCT-B, 62.5%, DST, 70% and OAT in 80%), FCT -A and B were abnormal in 10 of 14 patients. CFF was <38Hz in 77 patients (55%). Twelve (19.6%) of 61 patients in HE-L group and 30(46.8%) of 64 in HE-NL group (p=0.001) developed HE over median follow up of 14 mo (range 1-20 months). Readmission rate due to causes other than HE (HE-L vs. HE-NL, 9:6, p=ns) and deaths (HE-L vs. HE-NL, 5:11, p=0.18) in two groups were similar. Recurrence of overt HE was significantly associated with two or more abnormal psychometric tests after the recovery of an episode of HE (r=0.369, p=0.02). Conclusion: Lactulose is effective for prevention of recurrence of hepatic encephalopathy in patients with cirrhosis.Figure