L-ornithine L-aspartate (LOLA) is a combination of natural amino acids, and recent systematic reviews have acclaimed the positive impact of LOLA on the cognitive health and mental state of hepatic encephalopathy patients. Moreover, it assists in lowering the blood ammonia levels and plays a vital role in the prevention and management of overt hepatic encephalopathy (OHE). Though multiple studies have evaluated the role of LOLA, in both oral and intravenous form, for treatment and prophylaxis for hepatic encephalopathy, the evidence is still scarce and is of low quality.

In this double-blind placebo-controlled randomized control trial (RCT), the efficacy of intravenous LOLA in higher grades (III, IV) of overt hepatic encephalopathy (OHE) is evaluated. A group of 140 patients with OHE was randomized to either a combination of rifaximin, lactulose, and LOLA (n=70) or rifaximin, lactulose, and placebo (n=70). LOLA was administered as an intravenous infusion at a dose of 30 g daily over 24 h for five days.

After five days of treatment, the preliminary results in terms of reversal of OHE, improvement in OHE conditions, and mental health grade of the under-trial patients, were evaluated. The secondary outcomes were assessed based on ammonia levels in the blood and serum cytokine levels for the similar time frame. Other health parameters and recovery aspects were also analyzed, which include death related to liver disease or other causes, rate of recovery from OHE, length of hospital stay, and mortality. The results obtained in the initial evaluation were 88.57% in the LOLA group and 68.57% in patients in the placebo group. Amongst secondary outcome measures, there were significant reductions in ammonia blood levels, Interleukin 6 (IL-6), and Tumor necrosis factor (TNF)-alpha in the LOLA group. In addition, faster recovery and lower mortality rates were also observed in the LOLA group compared to the placebo group.

This study demonstrated that a combination of all three drugs (lactulose, rifaximin, and LOLA) has an additive effect in the reversal of OHE. The response rate reported with the combination of rifaximin, lactulose, and LOLA was 90%. Thus, it can be concluded that the combination of LOLA with lactulose and rifaximin is more effective than lactulose and rifaximin compositions in the prevention and treatment of hepatic encephalopathy, improving grades of HE, faster recovery time from encephalopathy, and imparts a beneficial effect on mortality, and serious adverse events.

Keywords: LOLA; Rifaximin; overt hepatic encephalopathy; mortality.

Source -Jain A, Sharma BC, Mahajan B, Srivastava S, Kumar A, Sachdeva S, et al. L-ornithine L-aspartate in acute treatment of severe hepatic encephalopathy: A double-blind randomized controlled trial. Hepatology. 2021 Nov 25. https:// doi.org/10.1002/hep.32255. Epub ahead of print. PMID: 34822189.