A systematic review and meta-analysis of published literature was conducted to analyse data from various studies showing the beneficial effect of L-ornithine L-aspartate (LOLA) for the prevention of overt hepatic encephalopathy (OHE) in patients with cirrhosis. Six randomized controlled trials involving 384 patients were finally selected for the meta-analysis with the objective to compare effects of oral and parenteral formulations of LOLA against placebo or no intervention. Of these, five were of high quality and had low risk of bias.

The effectiveness of LOLA was studied in four clinical presentations of OHE related to cirrhosis namely progression of MHE to OHE, prevention of the recurrence of OHE (secondary prophylaxis), primary prophylaxis of OHE associated with acute variceal bleeding and prophylaxis of OHE associated with transjugular intrahepatic stent shunt (TIPSS) procedure. In three RCTs, the risk of progression of MHE to OHE declined significantly after LOLA treatment with relative risk of 0.23.

Pooled analysis showed that compared to placebo or the no intervention approach, LOLA was effective in preventing OHE (RR 0.38) in all six trials. LOLA was also effective in the primary prophylaxis of OHE after acute variceal bleeding (RR 0.42) and post-TIPSS (RR 0.30). Blood ammonia levels were decreased considerably in these patients illustrating the ammonia-lowering action of LOLA.

This meta-analysis has for the first time demonstrated the effectiveness of LOLA in preventing OHE in patients with cirrhosis in diverse clinical settings. The authors expressed the hope that “the findings of the present review may stimulate further clinical research into the use of LOLA for primary and secondary OHE prophylaxis as well as trials of the use of LOLA for post-TIPSS OHE prophylaxis for which there remains an important unmet clinical need”.

 Butterworth RF, et al. Metab Brain Dis. 2020 Jan;35(1):75-81. doi: 10.1007/s11011-019-00463-8.