Secondary Prophylaxis of Hepatic Encephalopathy in Cirrhosis: A Double Blind Randomized Controlled Trial of l-Ornithine l-Aspartate Vs Placebo

Abstract

Background and Aim: Hepatic encephalopathy is associated with a poor prognosis. l-Ornithine l-aspartate has been useful in treatment of hepatic encephalopathy. There is no study on the prevention of recurrence of encephalopathy with l-ornithine l-aspartate. Methods: We conducted a double blind randomized controlled trial at a tertiary center OPD clinic. Consecutive cirrhotic patients who recovered from HE were randomized to receive LOLA (6 g thrice daily) or similar amount of placebo by computer based random numbers for 6 months. Patients were assessed by number connection tests or figure connection tests (if illiterate), digit symbol test, serial dotting test, line tracing test, critical flicker frequency test, arterial ammonia and Sickness impact profile scores at inclusion. Primary end point was development of overt HE. Results: Of 306 patients, 150 patients were enrolled. HE recurred in 9/73 (12.3%) and in 20/72 (27.7%) patients receiving LOLA and placebo respectively, P = 0.02 and hazard ratio = 0.389 (95% CI = 0.174–0.870). Mortality was similar in both groups (6.8% vs 13.8% P = 0.18). At 6 months follow up, there was significant change in the PHES (2.53 ± 2.18 vs −0.01 ± 1.92, P < 0.001), ammonia (−23.58 ± 14.8 vs 1.41 ± 13.34 μmol/L P < 0.001) and CFF (5.85 ± 4.82 vs 0.58 ± 4.53 P < 0.001) in patients treated with LOLA compared to placebo. The health related quality of life also improved in LOLA group compared to placebo (−7.89 ± 5.52 vs −0.95 ± 4.25 P = 0.001). On multivariate analysis only MELD score predicted the recurrence of overt HE with odds ratio 2.21 (95% CI: 1.526–3.204 P < 0.001). Conclusions: LOLA is effective in the secondary prophylaxis of HE and is associated with significant improvements in PHES, ammonia and CFF scores and HRQOL (Figure 1 and Table 1).Table 1Delta Change in Parameters in LOLA and Placebo Groups at 3 Months and 6 Months Compared to Baseline.ΔChangeLOLAPlaceboΔPHES 31.28 ± 1.670.30 ± 1.97<0.001ΔPHES 62.53 ± 2.18−0.01 ± 1.92<0.001ΔCFF 33.28 ± 3.650.39 ± 3.59<0.001ΔCFF 65.85 ± 4.820.59 ± 4.53<0.001ΔNH3 3−12.92 ± 9.04−0.66 ± 10.72<0.001ΔNH3 6−23.58 ± 14.81.41 ± 13.34<0.001ΔSIP 3−4.56 ± 3.27−0.74 ± 3.21<0.001ΔSIP 6−7.89 ± 5.52−0.95 vs 4.25<0.001Abbreviations: CTP: Child Turcotte Pugh score; MELD: model for end stage liver disease; PHES: pychometric hepatic encephalopathy scores; CFF: critical flicker frequency. Δ = Delta = change in value of parameters from baseline; 3 is at 3 months and 6 is at 6 months follow up; − value denotes decrease from the baseline and + value denotes increase from baseline. Open table in a new tab Abbreviations: CTP: Child Turcotte Pugh score; MELD: model for end stage liver disease; PHES: pychometric hepatic encephalopathy scores; CFF: critical flicker frequency. Δ = Delta = change in value of parameters from baseline; 3 is at 3 months and 6 is at 6 months follow up; − value denotes decrease from the baseline and + value denotes increase from baseline. The authors have none to declare.