l-Ornithine l-Aspartate (LOLA) for Hepatic Encephalopathy in Cirrhosis: Results of Randomized Controlled Trials and Meta-Analyses

Abstract

This manuscript represents an appraisal of the evidence in support of l-ornithine-l-aspartate (LOLA) for the management and treatment of hepatic encephalopathy (HE) in cirrhosis. Meta-analyses of randomized controlled trials (RCTs) conducted over the last two decades generally reveal evidence of benefit of LOLA in a range of clinical presentations. This included improvement of mental state grade in overt HE (OHE) assessed by West Haven criteria as well as in minimal HE (MHE) assessed by psychometric testing where the oral formulation of LOLA was determined to be particularly effective. However, concerns over study quality were noted in one meta-analysis. Nevertheless, the concomitant lowering of fasting blood ammonia was reported in all RCTs using this endpoint. Network meta-analyses showed that LOLA appears to be comparable (or superior) in efficacy to non-absorbable disaccharides or probiotics. Emerging evidence from single RCTs show efficacy of LOLA for the treatment of post-transjugular intrahepatic portosystemic shunt (TIPSS) HE as well as for secondary HE prophylaxis. These findings provide support for the use of LOLA in the treatment of HE and future trials should focus on the use of LOLA for prophylaxis.

Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update

“…Few recent meta-analysis showed a positive role of LOLA in reduction of ammonia as well as improvement in encephalopathy. Hence, LOLA can be considered as a potentially beneficial therapy for ACLF patients with HE and/ or hyperammonemia [119]. However, a large prospective study would be needed.…”

l-Ornithine l-Aspartate (LOLA) for the Treatment of Hepatic Encephalopathy in Cirrhosis: Novel Insights and Translation to the Clinic

“…Emerging evidence from RCTs shows efficacy of LOLA for the treatment of post-TIPSS HE as well as for primary and secondary prophylaxis. If confirmed in larger analyses, these findings could provide a considerable basis of support for the use of LOLA in the prevention of HE in cirrhosis [5].…”

Safety and efficacy of hydroxyurea and eflornithine against most blood parasites Babesia and Theileria

“…DFMO inhibits ornithine decarboxylase, the primary enzyme required for polyamines putrescine and spermidine synthesis, which is needed for cell multiplication and differentiation and it enters trypanosomes through the amino acid transporter AAT6 [23]. Notably, DFMO also has anabolic, wound-healing, and immuno-enhancing effects as well as improves liver function and helps in the detoxification of harmful substances [24,25].…”