Prospects for the treatment of different phenotypes of nonalcoholic fatty liver disease complicated by hyperammonemia and sarcopenia: clinical study results

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Background: This study examined the effect of lowering ammonia levels on sarcopenia severity in patients receiving pharmacotherapy for different nonalcoholic fatty liver disease (NAFLD) phenotypes.

Materials and methods: Moreover, it identified the optimal treatment strategy for managing these comorbid conditions. This single-center, prospective, observational clinical study included 30 adult patients diagnosed with different forms of NAFLD (i.e., steatosis, steatohepatitis, fibrosis, and cirrhosis) who had elevated blood ammonia levels and exhibited signs of sarcopenia. The participants were divided into two groups, which included 15 patients each. Group 1 received standard treatment plus L-ornithine-L-aspartate (9 g/day orally), whereas group 2 received standard treatment alone. The treatment course lasted 4 weeks.

Results: The addition of L-ornithine-L-aspartate to standard therapy significantly reduced ammonia levels and improved sarcopenia markers in patients with NAFLD. The study confirmed previous evidence on the role of L-ornithine-L-aspartate in reducing hyperammonemia and hepatic encephalopathy in patients with NAFLD. Moreover, the findings showed sarcopenia regression in patients with NAFLD, including those without cirrhosis, following L-ornithine-L-aspartate intake for 4 weeks at a dose of 9 g/day.

Conclusions: Thus, ammonia-lowering agents, such as L-ornithine-L-aspartate, show promise. However, large-scale clinical trials are required to confirm their effectiveness in improving muscle strength loss and hyperammonemia. Further analysis of the relationship between NAFLD, sarcopenia, and hyperammonemia may lead to the development of personalized therapeutic strategies integrating pharmacologic treatments with lifestyle modifications. Addressing these issues through early diagnosis, targeted therapy, and interdisciplinary approaches is crucial for improving patient outcomes.

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作者简介

Michail E. Statsenko

Volgograd State Medical University

Email: naclo@mail.ru
ORCID iD: 0000-0002-3306-0312
SPIN 代码: 3646-5743

MD, Dr. Sci. (Medicine), Professor

俄罗斯联邦, Volgograd

Roman G. Myazin

Volgograd State Medical University

编辑信件的主要联系方式.
Email: naclo@mail.ru
ORCID iD: 0000-0002-2375-517X
SPIN 代码: 4804-3951

MD, Cand. Sci. (Medicine)

俄罗斯联邦, Volgograd

参考

  1. Ivashkin VT, Mayevskaya MV, Zharkova MS, et al. Clinical practice guidelines of the russian scientific liver society, Russian gastroenterological association, russian association of endocrinologists, Russian association of gerontologists and geriatricians and national society for preventive cardiology on diagnosis and treatment of non-alcoholic liver disease. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2022;32(4):104–140. EDN: EXTLXM doi: 10.22416/1382-4376-2022-32-4-104-140
  2. Lazebnik LB, Golovanova EV, Turkina SV, et al. Non-alcoholic fatty liver disease in adults: clinic, treatment. Guidelines for therapists, third version. Experimental and clinical gastroenterology. 2021;1(1):4–52. EDN: KJLOJV doi: 10.31146/1682-8658-ecg-185-1-4-52
  3. Angulo P, Kleiner DE, Dam-Larsen S, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149(2):389–397e.10. doi: 10.1053/j.gastro.2015.04.043
  4. Gómez A, Romero-Gómez M, Ampuero J. Glutaminolysis-ammonia-urea cycle axis, non-alcoholic fatty liver disease. progression and development of novel therapies. J Clin Transl Hepatol. 2022;10(2):356–362. EDN: RJTHZO doi: 10.14218/JCTH.2021.00247
  5. Ivashkin VT, Drapkina OM, Maev IV, et al. Prevalence of non-alcoholic fatty liver disease in out patients of the Russian Federation: DIREG 2 study results. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2015;25(6):31–41. EDN: VOXFQP
  6. Zykina EY, Simonova ZG. Hyperammonemia in patients with stable angina pectoris and nonalcoholic fatty liver disease at the steatosis stage. Experimental and clinical gastroenterology. 2023;(8):57–65. EDN: LAUZAW doi: 10.31146/1682-8658-ecg-216-8-57-65
  7. Lazebnik LB, Golovanova EV, Alekseenko SA, et al. Russian consensus «Hyperammonemia in adults» (Version 2021). Experimental and clinical gastroenterology. 2021;(3):97–118. EDN: IXZDGZ doi: 10.31146/1682-8658-ecg-187-3-97-118
  8. Nadinskaya MYu, Mayevskaya MV, Bakulin I.G, et al. Diagnostic and prognostic value of hyperammonemia in patients with liver cirrhosis, hepatic encephalopathy, and sarcopenia (experts’ agreement). Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2024;34(1): 85–100. EDN: NTMBCP doi: 10.22416/1382-4376-2024-34-1-85-10
  9. Manickam R, Duszka K, Wahli W. PPARs and microbiota in skeletal muscle health and wasting. Int J Mol Sci. 2020;21(21):8056. EDN: UORSRU doi: 10.3390/ijms21218056
  10. Gale CR, Martyn CN, Cooper C, et al. Grip strength, body composition, and mortality. In J Epidemiol. 2007;36(1):228–235. EDN: IQBWBL doi: 10.1093/ije/dyl224
  11. Yang YJ, Kim DJ. An Overview of the molecular mechanisms contributing to musculoskeletal disorders in chronic liver disease: osteoporosis, sarcopenia, and osteoporotic sarcopenia. Int J Mol Sci. 2021;22(5):2604. EDN: DYYRPC doi: 10.3390/ijms22052604
  12. Axelrod CL, Dantas WS, Kirwan JP. Sarcopenic obesity: emerging mechanisms and therapeutic potential. Metabolism. 2023;146:155639. EDN: LAEBMZ doi: 10.1016/j.metabol.2023.155639
  13. Cruz-Jeentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis. report of the European Working Group on sarcopenia in older people. Age Ageing. 2010;39(4):412–423. EDN: NZQOZL doi: 10.1093/ageing/afq034
  14. Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16–31. EDN: OIPUXJ doi: 10.1093/ageing/afy169
  15. De Sire R, Rizzatti G, Ingravalle F, et al. Skeletal muscle-gut axis: Emerging mechanisms of sarcopenia for intestinal and extra intestinal diseases. Minerva Gastroenterol. Dietol. 2018;64(4): 351–362. doi: 10.23736/S1121-421X.18.02511-4
  16. Malmstrom TK, Morley JE. SARC-F: a simple questionnaire to rapidly diagnose sarcopenia. JAMDA. 2013;14(8):531–532. doi: 10.1016/j.jamda.2013.05.018
  17. Lim S, Kim JH, Yoon JW, et al. Sarcopenic obesity: prevalence and association with metabolic syndrome in the Korean longitudinal study on health and aging (KLoSHA). Diabetes Care. 2010;33(7): 1652–1654. doi: 10.2337/dc10-0107
  18. Dasarathy S, Merli M. Sarcopenia from mechanism to diagnosis and treatment in liver disease. J. Hepatol. 2016;65(6):1232–1244. EDN: YWEEKF doi: 10.1016/j.jhep.2016.07.040
  19. Myazin RG. Sarcopenia and non-alcoholic fatty liver disease. Experimental and clinical gastroenterology. 2024;222(2):120–130. EDN: NPLWSY doi: 10.31146/1682-8658-ecg-222-2-120-130
  20. Abenavoli L, Statsenko M, Scarlata GGM, et al. Sarcopenia and metabolic dysfunction-associated steatotic liver disease: a narrative review. Livers. 2024;4(4):495–506. EDN: MQMTDE doi: 10.3390/livers4040035

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1. JATS XML
2. Fig. 1. Measuring handgrip strength

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3. Fig. 2. Severity of sarcopenia (SARC-F questionnaire)

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4. Fig. 3. Ammonia level in capillary blood

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