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

Excerpt

The principal objective of this dedicated Supplement to the journal focuses on the demystification of the concept of hepatic encephalopathy (HE) in cirrhosis. Particular attention is paid to the definition of HE, its subtypes in relation to the nature and severity of liver impairment, the scales used for assessment of HE grades, and approaches to diagnosis. The effects of HE in cirrhosis on quality-of-life issues for the patients and their families and caregivers are given particular prominence. An update on the pathology and pathobiology of HE in cirrhosis follows in which the roles of exposure of the brain to gut-derived toxins (ammonia, manganese), inflammation and enhanced central inhibitory neurotransmission are described. The following manuscript in the Supplement deals with the pharmacokinetics/pharmacodynamics of l-ornithine l-aspartate (LOLA), following its discovery as an effective ammonia-lowering agent some 50 years ago. Details relating to LOLA’s mechanisms of action and a critical review of the evidence from clinical trials and meta-analyses in support of the efficacy of LOLA for the treatment of HE in cirrhosis is included together with preliminary evidence of efficacy in non-alcoholic fatty liver disease (NAFLD). …