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).
Keywords: Cirrhosis; Hepatic encephalopathy; Lactulose; Prophylaxis; Upper gastrointestinal bleeding.