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

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