Liver «under control»: effective use of diagnostic capabilities in clinical practice | Ukrainian Medical Journal

Сhronic liver disease (CLD) is one of the major problems of the health care system in the world. In the early stages of the disease, it is not characterized by pronounced clinical symptoms, which leads to delays in seeking medical care. Therefore, it is important to identify groups at increased risk of developing CLD and refer such patients to additional examinations with the aim of early diagnosis. However liver tests in patients with CLD may be within the normal range, which causes new challenges in diagnosis. The violation in the metabolic function of the liver was already noted at the stage of steatosis, leading to a lowering of ammonium excretion and the development of hyperammonemia in the early stages of CLD and the progression of the disease. Early detection of hyperammonemia can prevent the progression of CLD and become a new therapeutic target. Original L-ornithine-L-aspartate detoxifies ammonium and reduces the severity of hyperammonemia, which is characterized by the decrease in contractility and deactivation of the liver stellate cells, the increase in endothelial NO-synthase activity, oxide nitrogen production and suppressing the development of liver fibrosis.

References

1. Cheemerla S., Balakrishnan M. (2021) Global epidemiology of chronic liver disease. Clin. Liver Dis. (Hoboken), 17(5): 365–370. DOI: 10.1002/cld.1061.
2. Björkström K., Franzén S., Eliasson B. et al. (2016) Risk factors for severe liver disease in patients with type 2 diabetes. Clin. Gastroenterol. Hepatol., 17(13): 2769–2775.
3. Pimpin L., Cortez-Pinto H., Negro F. et al. (2018) Burden of liver disease in Europe: epidemiology and analysis of risk factors to identify prevention policies. J. Hepatol., 69(3): 718–735.
4. Sotoudehmanesh R., Sotoudeh M., Ali-Asgari A. et al. (2006) Silent liver diseases in autopsies from forensic medicine of Tehran. Arch. Iran Med., 9(4): 324–328.
5. Raszeja-Wyszomirska J., Lawniczak M., Marlicz W. et al. (2008) Non-alcoholic fatty liver disease — new view. Pol. Merkur Lekarski, 24(144): 568–571.
6. Lala V., Zubair M., Minter D.A. (2022) Liver Function Tests.
7. Шерлок Ш., Дули Д. (2002) Заболевания печени и желчных путей. Практическое руководство. (пер. с англ.). ГЭОТАР-Медиа, Москва, 864 с.
8. Вялов С.С. (2012) Алгоритмы диагностики. МЕДпресс-информ, Москва, 127 c.
9. Chalasani N., Younossi Z., Lavine J.E. et al. (2012) The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology, 55(6): 2005–2023. doi: 10.1002/hep.25762.
10. Підгірний Я.М. (2018) Гостра печінкова дисфункція і вагітність. Мед. неотл. сост., 3: 7–13.
11. Sharma A., Nagalli S. (2023) Chronic Liver Disease.
12. European Association for the Study of the Liver (2021) EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis. J. Hepatol., 75(3): 659–689. doi: 10.1016/j.jhep.2021.05.025.
13. Налапко К.К., Гетьманенко О.А., Купершмидт В.Р. та ін. (2012) Синдром эндогенной интоксикации и его гепатотропная коррекция в клинической практике. Укр. журн. екстрем. мед. імені Г.О. Можаєва, 13(2): 28–33.
14. Balcar L., Krawanja J., Scheiner B. et al. (2023) Impact of ammonia levels on outcome in clinically stable outpatients with advanced chronic liver disease. JHEP Rep., 5(4): 100682.
15. Kjærgaard K., Mikkelsen A.C.D., Wernberg C.W. et al. (2021) Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease-Current Knowledge, Mechanisms and Perspectives. J. Clin. Med., 10(4): 673. DOI: 10.3390/jcm10040673.
16. Kimelberg H.K. (2005) Astrocytic swelling in cerebral ischemia as a possible cause of injury and target for therapy. Glia, 50: 389–397.
17. De Chiara F., Habiesion A., Davies N. et al. (2017) Early increase in ammonia is a feature of Non-Alcogolic Fatty Liver Disease and the ammonia lovering drug, Ornithine Phenylacetate (OP-OCR002) prevents progression of fibrosis in a rodent model. J. Clin. Exp. Hepatol., 7(1): S73–S74. DOI: 10.1016/j.jceh.2017.01.099.
18. clinicaltrials.gov/ct2/show/NCT01847651.
19. Zafiris O., Kircheis G., Rood H.A. et al. (2004). Neural mechanism underlying impaired visual judgement in the dysmetabolic brain: an fMRI study. Neuroimage, 22(2): 541–552.
20. Butterworth R.F. (2019) l-Ornithine l-aspartate: multimodal therapeutic agent for hyperammonemia and hepatic encephalopathy in cirrhosis. J. Pharmacol. Pharm. Res., 2(3): 1–7.
21. De Chiara F., Thomsen K.L., Habtesion A. et al. (2020) Ammonia Scavenging Prevents Progression of Fibrosis in Experimental Nonalcoholic Fatty Liver Disease. Hepatology, 71(3): 874–892.
22. Panasiuk A. (2014) Encefalopatia wątrobowa. In: Forum Medycyny Rodzinnej, 8(2): 64–75.
23. Gutiérrez-de-Juan V., López de Davalillo S., Fernández-Ramos D. et al. (2017) A morphological method for ammonia detection in liver. PLoS One, 12: e0173914.
24. Stauch S., Kircheis G., Adler G. et al. (1998) Oral L-ornithine-L-aspartate therapy of chronic hepatic encephalopathy: results of a placebo-controlled double-blind study. J. Hepatol., 28(5): 856–864.
25. Kircheis G., Wettstein M., vom Dahl S., Häussinger D. (2002) Clinical efficacy of L-ornithine-L-aspartate in the management of hepatic encephalopathy. Metab. Brain Dis., 17(4): 453–462.
26. Bai M., He C., Yin Z. et al. (2014) Randomised clinical trial: L-ornithine-L-aspartate reduces significantly the increase of venous ammonia concentration after TIPSS. Aliment. Pharmacol. Ther., 40(1): 63–71. DOI: 10.1111/apt.12795.
27. Geng X.-X., Huang R.-G., Lin J.-M. et al. (2016) Transient Elastography in Clinical Detection of Liver Cirrhosis: A Sys-tematic Review and Meta-analysis. Saudi J. Gastroenterol., 22(4): 294–303. doi: 10.4103/1319-3767.187603.
28. Sporea I., Popescu A., Sirli R. (2008) Why, who and how should perform liver biopsy in chronic liver diseases. World J. Gastroenterol., 14(21): 3396–3402.