Recent trends in studying of alcohol-induced liver disease
Abstract
The aim of review. To analyze main epidemiologic tendencies of development of alcoholic liver disease, mechanisms of its development, mortality in this population of patients. To discuss an option of new targets for treatment of this disease.
Original positions. Alcohol abuse is the third leading cause of morbidity and mortality in the young age. In the studies it was demonstrated, that there is significant difference in death rate of liver cirrhosis between European countries. Disease risk factors include: amount of taken alcohol, its type, frequency of use, female gender, excessive body weight. Besides damaging effect, in response to admission of alcohol processes of protection and neogenesis of the liver through activation of IL-6, IL-22 receptors, STAT-proteins system are initiated. Mechanism of TNFα action, resulting in apoptosis of hepatocytes through activation of acidic sphingomyelinase is investigated.
Conclusion. Application of acidic sphingomyelinase, influence on Kupffer's cells phenotype, cannabinoids receptors as new targets for treatment of alcoholic liver disease is possible. At treatment of patients with severe alcohol-induced hepatitis corticosteroids considerably increasing 28-day's survival rate are actively applied. To increase efficacy of treatment of acute alcoholic hepatitis the issue of addition to standard treatment by glucocorticosteroids IL-22 is taken into account.
About the Authors
I. I. Komkova
ГБОУ ВПО «Первый Московский государственный медицинский университет им. И.М. Сеченова»
Russian Federation
Russian Federation
M. S. Zharkova
ГБОУ ВПО «Первый Московский государственный медицинский университет им. И.М. Сеченова»
Russian Federation
Russian Federation
M. V. Mayevskaya
ГБОУ ВПО «Первый Московский государственный медицинский университет им. И.М. Сеченова»
Russian Federation
Russian Federation
References
1. Ивашкин В.Т., Буеверов А.О. Рациональная фармакотерапия в гепатологии: Руководство для практических врачей. – М.: Литтерра, 2009.
2. Ивашкин В.Т., Буеверов А.О., Маевская М.В. Дифференцированный подход к лечению алкогольных поражений печени // Клин. перспективы гастроэнтерол. гепатол. – 2005. – № 5. – С. 8–13.
3. Ивашкин В.Т., Маевская М.В. Алкогольно-вирусные заболевания печени. – М.: Литтерра, 2007. – С. 85–118.
4. Маевская М.В., Морозова М.А., Ивашкин В.Т. Алгоритм ведения пациентов с алкогольной болезнью печени. – Рос. журн. гастроэнтерол. гепатол. колопроктол. – 2007. – Т. 17, № 6. – С. 1–10.
5. Becker U, Grønbaek M, Johansen D, Sørensen TI. Lower risk for alcohol-induced cirrhosis in wine drinkers. Hepatology. 2002; Apr;35(4): 868–75.
6. Bellentani S, Saccoccio G, Costa G, et al. Drinking habits as cofactors of risk for alcohol induced liver damage. Gut 1997;41:845–50 doi:10.1136/gut.41.6.845.
7. Bone-Larson CL, Simpson KJ, Colletti LM, et al. The role of chemokines in the immunopathology of the liver. Immunol Rev, 2000; 177: 8–20.
8. Burra P, Senzolo M, Adam R, et al. Liver Transplantation for Alcoholic Liver Disease in Europe: A Study from the ELTR (European Liver Transplant Registry). American Journal of Transplantation, 2010; 10; 1: 138–48.
9. Dey A, Cederbaum AI. Alcohol and oxidative liver injury. Hepatology. 2006; 43(2) Suppl 1: 63–74.
10. Gao B. Cytokines, STATs and liver disease. Cell Mol Immunol. 2005; 2(2): 92–100.
11. García-Ruiz C., Colell A., Mari M., et al. Direct effect of ceramide on the mitochondrial electron transport chain leads to reactive oxygen species. Role of mitochondrial glutathione. J. Biol. Chem. 1997; 272: 11369–77.
12. García-Ruiz C., Colell A., París R., FernándezCheca J.C. Direct interaction of GD3 ganglioside with mitochondria generates reactive oxygen species followed by mitochondrial permeability transition, cytochrome c release and caspase activation. FASEB J. 2000; 14: 847–58.
13. Gordon S. Alternative activation of macrophages. Nat Rev Immunol. 2003; Jan; 3(1):23–35.
14. Hannun YA, Luberto C, Argraves KM. Enzymes of sphingolipid metabolism: from modular to integrative signaling. Biochemistry. 2001; 40: 4893–903.
15. Hart C, Morrison D, Batty G, et al. Effect of body mass index and alcohol consumption on liver disease: analysis of data from two prospective cohort studies. BMJ. 2010; 340: 1240.
16. Hatton J, Burton A, Nash H, et al. Drinking patterns, dependency and life-time drinking history in alcoholrelated liver disease. Addiction. 2009; 104; 4:587–92.
17. Jeong W.I., Osei-Hyiaman D., Park O., et al. Paracrine activation of hepatic CB1 receptors by stellate cellderived endocannabinoids mediates alcoholic fatty liver. Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
18. Julien B., Grenard P., Teixeira-Clerc F., et al. Antifibrogenic role of the cannabinoid receptor CB2 in the liver. Gastroenterology. 2005; 128: 742–55.
19. Ki S.H., Park O., Zheng M., et al. Interleukin-22 treatment ameliorates alcoholic liver injury in a murine model of chronic-binge ethanol feeding: role of signal transducer and activator of transcription 3. Hepatology. 2010; Oct;52(4): 1291–300.
20. Kovalovich K., DeAngelis R.A., Li W., et al. Increased toxin-induced liver injury and fibrosis in interleukin-6deficient mice. Hepatology. 2000; 31: 149.
21. Kroemer G., Reed J.C. Mitochondrial control of cell death. Nat. Med. 2000; 6: 513–9.
22. Liu B. et al. Body mass index and risk of liver cirrhosis in middle aged UK women: prospective study. BMJ. 2010; 340: 912.
23. Lotersztajn S., Teixeira-Clerc F., Julien B., et al. CB2 receptors as new therapeutic targets during liver diseases. Br J Pharmacol. 2008; 153: 286–9.
24. Louvet A., Wartel F., Castel H., et al. Infection in patients with severe alcoholic hepatitis treated with steroids: early response to therapy is the key factor. Gastroenterology. 2009; 137; 2:541–8.
25. Martinez F.O., Sica A., Mantovani A., Locati M. Macrophage activation and polarization. Front Biosci. 2008; 13: 453–61.
26. Mathurin P., O’Grady J., Carithers R., et al. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis: meta-analysis of individual patient data. Gut. 2011; 60: 255–60.
27. Mato J.M., Cámara J., Fernández de Paz J., et al. S-Adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol. 1999; Jun; 30(6):1081–9.
28. McClain C.J., Barve S., Deaciuc I., Hill D.B. Tumor necrosis factor and alcoholic liver disease. Alcohol Clin Exp Res. 1998; 22:248–52.
29. Merrill A.H., Jr, Lingrell S., Wang E., et al. Sphingolipid biosynthesis de novo by rat hepatocytes in culture. Ceramide and sphingomyelin are associated with, but not required for, very low-density lipoprotein secretion. J. Biol. Chem. 1995; 270:13834–41.
30. Nagy L.E. Recent insights into the role of the innate immune system in the development of alcoholic liver disease. Exp Biol Med (Maywood). 2003; 228(8): 882–90.
31. Rehm J., Taylor B. Global burden of disease from alcohol, illicit drugs and tobacco. Drug and Alcohol Review. 2006; 25; 6:503–13.
32. Szabo G. New insights into the molecular mechanisms of alcoholic hepatitis: a potential role for NF-kB activation? J Lab Clin Med. 2000; 135: 367–9.
33. Taub R. 2003. Hepatoprotection via the IL-6/Stat3 pathway. J. Clin. Invest.112:978.
34. Teixeira-Clerc F., Julien B., Grenard P., et al. CB1 cannabinoid receptor antagonism: a novel strategy for the treatment of liver fibrosis. Nature Medicine. 2006; 12:671–6.
35. Tsukamoto H., Lu S.C. Current concepts in the pathogenesis of alcoholic liver injury. FASEB J. 2001; 15(8):1335–49.
36. Zhang X., Tachibana S., Wang H., et al. Interleukin-6 is an important mediator for mitochondrial DNA repair after alcoholic liver injury in mice. Hepatology. 2010; Dec; 52(6):2137 47. doi: 10.1002/hep.23909. Epub 2010 Oct 7.
37. http://www.multiwebcast.com/easl/2010/athens
Review
For citations:
Komkova I.I., Zharkova M.S., Mayevskaya M.V. Recent trends in studying of alcohol-induced liver disease. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2011;21(6):33-41. (In Russ.)
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