Secondary prophylaxis of hepatic encephalopathy: an open-label randomized controlled trial of lactulose versus placebo.

BACKGROUND & AIMS: 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], and object assembly test [OAT]), critical flicker frequency test, and blood ammonia at inclusion. Primary end point 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 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).

CONCLUSIONS: Lactulose is effective for prevention of recurrence of HE in patients with cirrhosis.