L-Ornithine L-Aspartate for Prevention and Treatment of Hepatic Encephalopathy in Patients with Cirrhosis

Abstract

In cirrhosis, the loss of metabolic capacity of periportal and perivenous hepatocytes coupled with the development of portal-systemic shunting frequently results in severe hyperammonemia. Molecular Imaging and Spectroscopic techniques reveal increases in the cerebral metabolic rate for ammonia and increased brain glutamine as a function of the severity of hepatic encephalopathy [HE]. L-Ornithine L-Aspartate [LOLA] is effective for the lowering of blood, muscle and brain ammonia and does so via three independent mechanisms namely [i] the stimulation of ammonia removal via the urea cycle in residual hepatocytes, [ii] prevention of hepatocellular damage due to the production of antioxidants [glutathione, glutamine] and [iii] the prevention of muscle wasting [sarcopenia] thus protecting the ammonia-detoxification pathway via muscle glutamine synthesis. Results of RCTs, systematic reviews and meta-analyses provide evidence for the efficacy of LOLA for the prevention and treatment of HE in all its forms [MHE, OHE, episodic HE, post-TIPSS HE] and for primary, secondary and post-TIPSS prophylaxis. Keywords: L-ornithine L-aspartate; LOLA; Hepatic encephalopathy; Cirrhosis; Treatment; Prevention; Prophylaxis; Ammonia; Hepatoprotection; Sarcopenia; Combination therapy