Clinical significance of hyperammonemia in non-alcoholic fatty liver disease

The review discusses the clinical significance of hyperammonemia and hyperammonihistia (tissue ammonia accumulation) in non-alcoholic (metabolic dysfunction-associated) fatty liver disease. Elevated blood and tissue ammonia levels can be observed already at pre-cirrhotic stages (in 40–78% of patients) and are not only a consequence but also a factor of disease progression, making it an independent pathogenetic target. Hyperammonemia exacerbates hepatocellular injury (through impairment of autophagy and epigenetic suppression of enzymes of the ornithine cycle), contributes to the development of sarcopenia, fatigue, cognitive and other neuropsychiatric impairments, and worsens the course of comorbid conditions. Key non-pharmacological approaches include the Mediterranean diet with adequate protein intake and regular physical activity combining aerobic and resistance exercise. From a pathogenetic pharmacotherapy perspective, the use of L-ornithine L-aspartate (LOLA) is justified, as it activates the urea cycle in the liver and the glutamine pathway in skeletal muscle. By reducing intracellular ammonia concentrations, LOLA helps alleviate mitochondrial dysfunction, restore autophagic processes, and slow the activation of hepatic stellate cells, which may in turn slow down the progression of steatosis, inflammation, and fibrosis. Course administration of LOLA at doses of 9–12 g per day for at least 12 weeks has been shown to reduce ammonia levels, decrease steatosis, improve cognitive function, enhance exercise tolerance, and improve patients’ quality of life. The experts emphasize that the decision to initiate therapy may be based on clinical manifestations (hepatogenic weakness, cognitive impairment, sarcopenia), even in the absence of routine monitoring of blood ammonia levels. The review was conducted in a narrative fashion without the use of systematic methodology. A targeted search of Russianand English-language publications was carried out using PubMed, eLIBRARY.RU, the Cochrane Library, and other databases.