Role of lactulose for prophylaxis against hepatic encephalopathy in cirrhotic patients with upper gastrointestinal bleeding: A randomized trial.

BACKGROUND

We aimed to assess the efficacy of lactulose as prophylaxis against hepatic encephalopathy (HE) in cirrhotic patients with acute upper gastrointestinal bleeding (AUGIB).

METHODS

We conducted a randomized, double-blinded, placebo-controlled, multicenter study from October 2012 to February 2014. Cirrhotic patients presenting with AUGIB (aged 18-80 years, without HE at the time of admission) were enrolled and randomized to receive blinded medications (both physically indistinguishable), labeled "Lactulose A" and "Lactulose B" for 5 days along with standard treatment depending on the type of bleeding (variceal and nonvariceal). The primary endpoint was the development of overt HE according to the West-Haven criteria. Modified intention-to-treat analysis was performed.

RESULTS

Forty-six patients completed the protocol: Lactulose A (placebo, n = 22) and Lactulose B (lactulose, n = 24). There was no significant difference in baseline characteristics and clinical outcomes between the two groups. Nine (19.6%) patients developed HE: five (22.7%) in the placebo group and four (16.7%) in the lactulose group (p = 0.718). One patient (2.2%) died in lactulose group. All patients tolerated the medication and no significant difference in adverse effects was detected (59.1% in placebo vs. 50.0% in lactulose group, p = 0.536). On multivariate analysis, increased baseline Child-Turcotte-Pugh (CTP) score (odds ratio [OR] 2.176; 95% confidence interval [CI] 1.012-4.681, p = 0.047) and presence of diarrhea (OR 16.261; 95% CI 1.395-189.608, p = 0.026) were independent risk factors for the development of HE.

CONCLUSION

Five-day lactulose is ineffective as prophylaxis against HE in cirrhotic patients with AUGIB. Unnecessary treatment with laxatives should be avoided in these patients.

TRIAL REGISTRATION

Clinical trial registry number TCTR20200526003 (retrospectively registered).