Efficacy of L-ornithine L-aspartate for minimal hepatic encephalopathy in patients with cirrhosis: A meta-analysis of randomized controlled trials

Abstract

Background and study aims: Minimal hepatic encephalopathy (MHE) is an early stage of hepatic encephalopathy (HE) and is highly prevalent. The efficacy of L-ornithine L-aspartate (LOLA) for the treatment of HE is well known but its role in MHE remains uncertain. The objectives of the current study were to evaluate the efficacy of LOLA for the treatment of MHE in patients with cirrhosis.

Methods: The Cochrane Library, PubMed, EMBASE, Web of Science and Ovid databases were searched. Only randomized controlled trials (RCTs) that compared the efficacy of LOLA with placebo or no intervention for the treatment of MHE in patients with cirrhosis were included from inception to January 2023. The primary outcomes were reversal of MHE and development of overt hepatic encephalopathy (OHE).

Results: Overall, six RCTs comprising 292 patients were included. Compared with placebo or no intervention, LOLA was more effective in reversing MHE (RR = 2.264, 95 % CI = 1.528, 3.352, P = 0.000, I² = 0.0 %) and preventing progression of OHE (RR = 0.220, 95 % CI = 0.076, 0.637, P = 0.005, I² = 0.0 %). Based on subgroup analyses, oral LOLA treatment appeared more likely to reverse MHE (RR = 2.648, 95 % CI = 1.593, 4.402, P = 0.000, I² = 0.0 %), intravenous LOLA treatment yielded a similar probability of reversing MHE (RR = 1.669, 95 % CI = 0.904, 3.084, P = 0.102, I² = 0.0 %). LOLA did not show a superior possibility in reducing mortality (RR = 0.422, 95 % CI = 0.064, 2.768, P = 0.368, I² = 0.0 %) and ammonia levels (SMD = 0.044, 95 % CI = -0.290, 0.379, P = 0.795, I² = 0.0 %) compared with placebo or no intervention.

Conclusions: LOLA has significant beneficial effects on reversal of MHE and prevention of OHE in patients with cirrhosis compared with placebo or no intervention.

Keywords: Cirrhosis; Efficacy; L-ornithine L-aspartate; Minimal hepatic encephalopathy; Randomized controlled trials.