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Abstract
Current statistical data show a sharp global increase in alcoholic liver disease (ALD), which is often associated with the onset of alcoholic pancreatitis. According to estimates, Ukraine has one of the highest rates of ALD mortality worldwide; it likely surpasses rates in Europe, the USA, Canada, Brazil, Australia, Indonesia, Africa, and Russia.
The normal course of ALD is well-known and starts with liver steatosis and alcoholic hepatitis, progressing to liver cirrhosis and hepatocellular carcinoma. Alcohol’s toxic effects are not limited to the liver; it has a harmful impact on almost all organs and tissues, including the pancreas, brain, cardiovascular system, reproductive organs, bone tissue, hematopoietic organs, and the stimulation of carcinogenesis. The basic understanding of the pathophysiology of ALD has not changed: the damaging effects of acetaldehyde and other metabolic alterations, such as disturbances in the metabolism of bile acids (BA), including their enterohepatic circulation, are the core of this disorder. One of the most significant nuclear BA receptors, the farnesoid X-receptor (FXR), affects the metabolism of bile acidosis (BA) on two levels: it limits the synthesis of bile acid in the liver and decreases enterohepatic circulation activity while also restoring normal lipid metabolism. Systemic or extrahepatic effects are mediated by FXR, which is expressed not just in the liver but also in the pancreas and a number of other organs and systems. ALD therapy methods are regulated by several international guidelines, namely EASL (2018), AASLD (2019), and ALEH (2019). In addition to conventional therapy, innovative and promising ways to treat using S-adenosine methionine (SAM) are being explored. SAM is a promising medication for the treatment of alcoholic pancreatitis and ALD because of its antagonistic activity on FXR, BSEP, and NTCP, the main proteins and receptors involved in ALD pathophysiology. It also has anti-inflammatory, anti-cholestatic, antitumor, and antidepressant qualities.
References
Abbas D., Ciricillo J. A., Elom H. A., Moon A. M. extrahepatic health effects of alcohol use and alcohol-associated liver disease. Clin. Ther. 2023. Vol. 45, No 12. P. 1201–1211.
American Association for the Study of Liver Diseases; Latin American Association for the Study of the Liver; European Association for the Study of the Liver. A call for unity: The path towards a more precise and patient-centric nomenclature for NAFLD. Ann. Hepatol. 2023. Vol. 28, No 4. P. 101115.
Anderson K., Gayer C. P. The pathophysiology of farnesoid X receptor (FXR) in the GI tract: inflammation, barrier function and innate immunity. Cells. 2021. Vol. 10, No 11. P. 3206.
Arab J. P., Roblero J. P., Altamirano J., Bessone F., Araujo R. C., Higuera-De la Tijera F., Restrepo J. C., Torre A., Urzua A., Simonetto D. A., Abraldes J. G. Alcohol-related liver disease: Clinical practice guidelines by the Latin American Association for the Study of the Liver (ALEH). Ann. Hepatol. 2019. Vol. 18, No 3. P. 518–535.
Cancer Research UK. How does the alcohol cause cancer? 2023. URL: https://blogs.biomedcentral.com/bmcseriesblog/2016/11/30/worrying-gaps-peoples-awareness-alcohol-cancer/ (Last accessed: 06.03.2024).
Chaudhry H., Sohal A., Iqbal H., Roytman M. Alcohol-related hepatitis: A review article. World J. Gastroenterol. 2023. Vol. 29, No 17. P. 2551–2570.
Crabb D. W., Im G. Y., Szabo G., Mellinger J. L., Lucey M. R. Diagnosis and treatment of alcohol-associated liver diseases: 2019 Practice Guidance From the American Association for the Study of Liver Diseases. Hepatology. 2020. Vol. 71, No 1. P. 306–333.
Devarbhavi H., Asrani S. K., Arab J. P., Nartey Y. A., Pose E., Kamath P. S. Global burden of liver disease: 2023 update. J. Hepatol. 2023. Vol. 79, No 2. P. 516–537.
Ding C., Wang Z., Dou X., Yang Q., Ning Y., Kao S., Sang X., Hao M., Wang K., Peng M., Zhang S. Farnesoid X receptor: from structure to function and its pharmacology in liver fibrosis. Aging Dis. 2023.
Dunn W., Shah V. Pathogenesis of alcoholic liver disease. Clin. Liver Dis. 2016. Vol. 20, No 3. P. 445–456.
European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of alcohol-related liver disease. J. Hepatol. 2018. Vol. 69, No 1. P. 154–181.
Gao B., Bataller R. Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology. 2011. Vol. 141, No 5. P. 1572–1585.
Han C. Y. Update on FXR biology: promising therapeutic target? Int. J. Mol. Sci. 2018. Vol. 19, No 7. P. 2069.
Hou Y., Zhai X., Wang X., Wu Y., Wang H., Qin Y., Han J., Meng Y. Research progress on the relationship between bile acid metabolism and type 2 diabetes mellitus. Diabetol. Metab. Syndr. 2023. Vol. 15, No 1. P. 235.
Kasper P., Lang S., Steffen H. M., Demir M. Management of alcoholic hepatitis: A clinical perspective. Liver Int. 2023. Vol. 43, No 10. P. 2078–2095.
Kong X., Li B., Deng Y., Ma X. FXR mediates adenylyl cyclase 8 expression in pancreatic β-cells. J. Diabetes Res. 2019. Vol. 2019. P. 8915818.
Liu Y., Bi T., Liu L., Gao Q., Shen G., Qin L. S-Adenosylmethionine synergistically enhances the antitumor effect of gemcitabine against pancreatic cancer through JAK2/STAT3 pathway. Naunyn. Schmiedebergs. Arch. Pharmacol. 2019. Vol. 392, No 5. P. 615–622.
Lu S. C., Gukovsky I., Lugea A., Reyes C. N., Huang Z. Z., Chen L., Mato J. M., Bottiglieri T., Pandol S. J. Role of S-adenosylmethionine in two experimental models of pancreatitis. FASEB J. 2003. Vol. 17, No 1. P. 56–58.
Mao H. Hepatoprotective effect of S-ademetionine in the treatment of intrahepatic cholestasis through farnesoid X receptor mechanism in rats. J. Biomol. Res. Ther. 2019. Vol. 8. P. 176.
Nath P., Anand A. Extrahepatic manifestations in alcoholic liver disease. J. Clin. Exp. Hepatol. 2022. Vol. 12, No 5. P. 1371–1383.
Noureddin M., Sander-Struckmeier S., Mato J. M. Early treatment efficacy of S-adenosylmethionine in patients with intrahepatic cholestasis: A systematic review. World J. Hepatol. 2020. Vol. 12, No 2. P. 46–63.
Onorato A., Napolitano A., Spoto S., Incorvaia L., Russo A., Santini D., Tonini G., Vincenzi B. S-adenosylmethionine supplementation may reduce cancer-related fatigue: a prospective evaluation using the FACIT-F questionnaire in colon cancer patients undergoing oxaliplatin-based chemotherapy regimens. Chemotherapy. 2021. Vol. 66, No 5–6. P. 161–168.
Peng T. R., Cheng H., Wu T. S-Adenosylmethionine (SAMe) as an adjuvant therapy for patients with depression: An updated systematic review and meta-analysis. Gen. Hosp. Psychiatry. 2024. Vol. 86. P. 118–126.
Popescu I. R., Helleboid-Chapman A., Lucas A., Vandewalle B., Dumont J., Bouchaert E., Derudas B., Kerr-Conte J., Caron S., Pattou F., Staels B. The nuclear receptor FXR is expressed in pancreatic beta-cells and protects human islets from lipotoxicity. FEBS Lett. 2010. Vol. 584, No 13. P. 2845–2851.
Raikhelson K. L., Kondrashina E. Аdеmethionine in the treatment of fatigue in liver diseases: a systematic review. Ter. Arkh. 2019. Vol. 91, No 2. P. 134–142.
Seitz H. K., Moreira B., Neuman M. G. Pathogenesis of alcoholic fatty liver a narrative review. Life (Basel). 2023. Vol. 13, No 8. P. 1662.
Sun F., Wang B. Alcohol and metabolic-associated fatty liver disease. J. Clin. Transl. Hepatol. 2021. Vol. 9, No 5. P. 719–730.
Tran Q. T., Sendler M., Doller J., Wiese M., Bolsmann R., Wilden A., Glaubitz J., Modenbach J. M., Thiel F. G., de Freitas Chama L. L., Weiss F. U. Role of bile acids and bile salts in acute pancreatitis: from the experimental to clinical studies. Pancreas. 2021. Vol. 50, No 1. P. 3–11.
Wan Y. D., Zhu R. X., Pan X. T., Sun T. W. Bile acid supplementation improves murine pancreatitis in association with the gut microbiota. Front. Physiol. 2020. Vol. 11. P. 650.
Way G. W., Jackson K. G., Muscu S. R., Zhou H. Key signaling in alcohol-associated liver disease: the role of bile acids. Cells. 2022. Vol. 11, No 8. P. 1374.
Yan C., Hu W., Tu J., Li J., Liang Q., Han S. Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease. J. Transl. Med. 2023. Vol. 21, No 1. P. 300.
Zhang Y., Ma R., Deng Q., Wang W., Cao C., Yu C., Li S., Shi L., Tian J. S-adenosylmethionine improves cognitive impairment in D-galactose-induced brain aging by inhibiting oxidative stress and neuroinflammation. J. Chem. Neuroanat. 2023. Vol. 128. P. 102232.
Zhou S., You H., Qiu S., Yu D., Bai Y., He J., Cao H., Che Q., Guo J., Su Z. A new perspective on NAFLD: Focusing on the crosstalk between peroxisome proliferator-activated receptor alpha (PPARα) and farnesoid X receptor (FXR). Biomed. Pharmacother. 2022. Vol. 154. P. 113577.