A randomised double blind controlled trial comparing rifaximin plus lactulose with lactulose alone in treatment of hepatic encephalopathy

Abstract

Background and Aims: Hepatic encephalopathy (HE) is associated with poor prognosis in cirrhosis. Majority of the drugs used in the treatment of HE are primarily directed at the reduction or elimination of the blood ammonia levels. We evaluated the efficacy and safety of rifaximin plus lactulose versus lactulose alone for treatment of overt hepatic encephalopathy. Methods: In prospective double blind randomized controlled trial, 120 patients with overt HE were randomized in 2 groups, group 1- lactulose (n=57) and group 2- lactulose plus rifaximin (n=63). Primary end point was reversal of hepatic encephalopathy. Secondary end points were mortality and hospital stay. Results: One hundred and twenty patients (mean age 39.4 ± 9.6 years; M: F 89:31) were included in study. Thirty seven (30.8%) patients were in Child-Turcotte-Pugh (CTP) class B and 83 (69.2%) were in CTP Class C. Mean CTP score was 9.7 ± 2.8 and MELD score was 24.6 ± 4.2. 22 (18.3%) had grade 2, 40 (33.3%) had grade 3 and 58 (48.3%) had grade 4 HE at the time of admission. Forty eight (76%) patients in group 2 compared to 29 (50.8%) patients in group 1 had reversal of HE (P<0.004). There was significant decrease in mortality after treatment with lactulose plus rifaximin versus lactulose alone (23.8% Vs 49.1%, P <0.05). Most common cause of death was sepsis (n=43, 55.8%), followed by hepatorenal syndrome (n=11, 25.6%) and GI bleed (n=8, 18.6%). There was no significant difference in cause of death in two groups. Patients in latulose plus rifaximin group had shorter hospital stay (5.8 ± 3.4 vs. 8.2 ± 4.6 days, P =0.001). Conclusions: Combination of lactulose plus rifaximin is more effective than lactulose alone in treatment of HE.