L-Ornithine L-Aspartate for the Prevention and Treatment of Liver Cirrhosis and its Complications

This chapter documents, in an evidence-based manner, current knowledge on the importance of L-ornithine L-aspartate (LOLA) for the prevention and treatment of cirrhosis and its complications. Electronic and manual searches of established databases using appropriate keywords revealed a wealth of pertinent data, including three high-quality recently published systematic reviews, each with meta-analysis detailing the results of randomized controlled trials (RCTs) on the efficacy of LOLA. Results confirmed that LOLA significantly lowered circulating ammonia with concomitant improvements of mental state in patients with minimal hepatic encephalopathy (MHE), overt hepatic encephalopathy (OHE), and episodic OHE where, in all cases, intravenous and oral formulations of LOLA functioned effectively. Combination therapy with LOLA, lactulose, and rifaximin led to more rapid improvement of OHE grade, rapid recovery of mental state, and decreased mortality compared to the lactulose/rifaximin combination alone. LOLA is also effective for the treatment of muscle wasting (sarcopenia) in cirrhosis. Improvements in liver function tests and MELD scores also occur following treatment with LOLA consistent with a hepatoprotective property where possible mechanisms include LOLA-induced synthesis of the antioxidant glutathione and of nitric oxide leading to improved hepatic microcirculation. A new dimension for LOLA in relation to cirrhosis is heralded by results of RCTs demonstrating its efficacy for the prevention of OHE resulting from a range of presentations, including OHE associated with variceal bleeding (primary prophylaxis), prevention of repeat episodes of OHE (secondary prophylaxis), post-TIPSS OHE prophylaxis as well as prevention of the deterioration of MHE to OHE in cirrhosis.