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

Abstract

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. 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], and object assembly test [OAT]), critical flicker frequency test, and blood ammonia at inclusion. Primary end point was development of overt HE. Of 300 patients with HE who recovered, 140 (46.6%) met the inclusion criteria and were included. There was a high prevalence of abnormal psychometry test results (NCT-A, 67.5%; NCT-B, 62.5%; DST, 70%; and OAT, 80%), and FCT-A and B were abnormal in 10 of 14 patients. Critical flicker frequency was <38 Hz in 77 patients (55%). Twelve (19.6%) of 61 patients in the HE-L group and 30 (46.8%) of 64 in the HE-NL group (P = .001) developed HE over a median follow-up of 14 months (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 = .18) in 2 groups were similar. Recurrence of overt HE was significantly associated with 2 or more abnormal psychometric tests after the recovery of an episode of HE (r = 0.369, P = .02). Lactulose is effective for prevention of recurrence of HE in patients with cirrhosis.