Primary Prophylaxis of Hepatic Encephalopathy in Patients with Cirrhosis: An Open Labeled Randomized Controlled Trial of Lactulose versus No Lactulose

Abstract

Purpose: Development of hepatic encephalopathy (HE) is associated with poor prognosis in patients with cirrhosis. Lactulose is used for the treatment of HE. There is no study on the prevention of HE using lactulose in patients who never had HE earlier. Methods: Consecutive cirrhotic patients who never had an episode of HE were randomized to receive lactulose (Gp-L) or no lactulose (Gp-NL). 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), serial dot test (SDT), line tracing test (LTT)] and critical flicker frequency test (CFF) at inclusion and after 3 months. These patients were followed monthly for development of overt HE. Results: Of 250 patients screened, 120(48%) meeting the inclusion criteria were randomized to Gp-L(n=60) and Gp-NL(n=60). Minimal hepatic encephalopathy (MHE) was present in (10/22, 45%) in Child A, (37/68, 54%) in Child B and (21/30, 70%) in Child C patients. Number of patients with MHE were comparable in two groups at baseline (Gp-L vx Gp-NL, 32:36, p=0.29). Lactulose improved MHE in 66% of patients in Gp-L. Patients diagnosed to have MHE had CFF significantly lower than those who did not had MHE in Gp-L (38.4±3.2 vs. 40.5±2.4 Hz, p=0.001) and in Gp-NL (38.8±2.8 vs. 41.7±3.2Hz, p=0.001). Twenty one (20%) of 105 patients followed over a median follow up of 12 mo developed an episode of overt HE. Six (11%) of 55 in the lactulose (Gp-L) group and 15(30%) of 50 in the Gp-NL (p=0.02) developed HE. Ten (20%) of 50 patients in Gp-NL and 5(9%) of 55 patients in Gp-L group died, p=0.16 Taking a cutoff < 38Hz sensitivity and specificity of CFF in predicting HE at baseline (52% and 77%) and at 3 month of treatment was (52% and 82%). On multivariate analysis CTP score and presence of MHE at baseline is significantly associated with development of HE. Conclusion: Lactulose is effective for primary prevention of hepatic encephalopathy in patients with cirrhosis.