A PEER-REVIEWED JOURNAL OF RESEARCH AND CLINICAL MEDICINEISSN 1727-2378 (Print)         ISSN 2713-2994 (Online)
Ru
En

Pathogenesis of Alcoholic Liver Disease: Current Insights

05 june 2015

Objective of the Review: To take a look at current insights into the pathogenesis of alcoholic liver disease (ALD).

Key Points: Based on the clinical and morphological features, the following three forms (stages) of liver damage can be identified: alcoholic steatosis, steatohepatitis and cirrhosis. Alcoholic steatosis is triggered by alcohol and results from enhanced lipogenesis caused by the activation of lipogenic gene expression and the inhibition of fatty acid oxidation. When inflammation develops, it leads to alcoholic steatohepatitis; ethanol metabolic products, endotoxins, ethanol-induced hypoxia, autophagy and other factors are important contributors. Fibrosis related to ALD is mediated by the activation of TLR4 receptors that is induced by bacterial lipopolysaccharides, the activation of hepatic stellate cells caused by acetaldehyde and the "profibrotic" effects of ethanol.

The authors also discuss the mechanisms and conditions required for the transformation of alcoholic liver cirrhosis into hepatocellular carcinoma.

Conclusion: In addition to ethanol, there are a number of other factors that contribute to the development of ALD, such as genetic, immune and epigenetic factors. The role of epigenetic factors should be further clarified.

I. G. Bakulin — Moscow Clinical Scientific and Practical Center at the Moscow Department of Healthcare. E-mail: igbakulin@yandex.ru

N. V. Shalikiani — Moscow Clinical Scientific and Practical Center at the Moscow Department of Healthcare. E-mail: nino_shalikiani@yahoo.com

 

Доктор.ру
5 June 07:47
REFERENCES
  1. Хомерики С. Г., Хомерики Н. М. Алкогольная болезнь печени: механизмы развития, морфологические проявления, дифференциальная диагностика и патогенетические подходы к терапии // Consilium Medicum. Гастроэнтерология. 2012. № 1. С. 27–34.
  2. Banerjee A., Apte U. M., Smith R., Ramaiah S. K. Higher neutrophil infiltration mediated by osteopontin is a likely contributing factor to the increased susceptibility of females to alcoholic liver disease // J. Pathol. 2006. Vol. 208. N 4. P. 473–485.
  3. Ding W. X., Manley S., Ni H. M. The emerging role of autophagy in alcoholic liver disease // Exp. Biol. Med. (Maywood). 2011. Vol. 236. N 5. P. 546–556.
  4. Donohue T. M. Jr. Alcohol-induced steatosis in liver cells // World J. Gastroenterol. 2007. Vol. 13. N 37. P. 4974–4978.
  5. Ely M., Hardy R., Longford N. T., Wadsworth M. E. Gender differences in the relationship between alcohol consumption and drink problems are largely accounted for by body water // Alcohol. Alcohol. 1999. Vol. 34. N 6. P. 894–902.
  6. Feldstein A. E., Gores G. J. Apoptosis in alcoholic and nonalcoholic steatohepatitis // Front. Biosci. 2005. N 10. P. 3093–3099.
  7. French S. W. The role of hypoxia in the pathogenesis of alcoholic liver disease // Hepatol. Res. 2004. Vol. 29. N 2. P. 69–74.
  8. Gao B., Bataller R. Alcoholic liver disease: pathogenesis and new therapeutic targets // Gastroenterology. 2011. Vol. 141. N 5. P. 1572–1585.
  9. Goist K. C. Jr., Sutker P. B. Acute alcohol intoxication and body composition in women and men // Pharmacol. Biochem. Behav. 1985. Vol. 22. N 5. P. 811–814.
  10. Gramenzi A., Caputo F., Biselli M., Kuria F. et al. Review article: alcoholic liver disease — pathophysiological aspects and risk factors // Aliment. Pharmacol. Ther. 2006. Vol. 24. N 8. P. 1151–1161.
  11. Halsted C. H. Nutrition and alcoholic liver disease // Semin. Liver Dis. 2004. Vol. 24. N 3. P. 289–304.
  12. Jagavelu K., Routray C., Shergill U., O'Hara S. P. et al. Endothelial cell toll-like receptor 4 regulates fibrosis-associated angiogenesis in the liver // Hepatology. 2010. Vol. 52. N 2. P. 590–601.
  13. Jeong W. I., Park O., Gao B. Abrogation of the antifibrotic effects of natural killer cells/interferon-gamma contributes to alcohol acceleration of liver fibrosis // Gastroenterology. 2008. Vol. 134. N 1. P. 248–258.
  14. Machida K., Tsukamoto H., Mkrtchyan H., Duan L. et al. Toll-like receptor 4 mediates synergism between alcohol and HCV in hepatic oncogenesis involving stem cell marker Nanog // Proc. Natl. Acad. Sci. USA. 2009. Vol. 106. N 5. P. 1548–1553.
  15. McMullen M. R., Pritchard M. T., Wang Q., Millward C. A. et al. Early growth response-1 transcription factor is essential for ethanol-induced fatty liver injury in mice // Gastroenterology. 2005. Vol. 128. N 7. P. 2066–2076.
  16. Mello T., Ceni E., Surrenti C., Galli A. Alcohol induced hepatic fibrosis: role of acetaldehyde // Mol. Aspects Med. 2008. Vol. 29. N 1–2. P. 17–21.
  17. Michalopoulos G. K. Liver regeneration // J. Cell. Physiol. 2007. Vol. 213. N 2. P. 286–300.
  18. Naveau S., Giraud V., Borotto E., Aubert A. et al. Excess weight risk factor for alcoholic liver disease // Hepatology. 1997. Vol. 25. N 1. P. 108–111.
  19. Purohit V., Brenner D. A. Mechanisms of alcohol-induced hepatic fibrosis: a summary of the Ron Thurman Symposium // Hepatology. 2006. Vol. 43. N 4. P. 872–878.
  20. Rao R. Endotoxemia and gut barrier dysfunction in alcoholic liver disease // Hepatology. 2009. Vol. 50. N 2. P. 638–644.
  21. Rouault T. A. Hepatic iron overload in alcoholic liver disease: why does it occur and what is its role in pathogenesis? // Alcohol. 2003. Vol. 30. N 2. P. 103–106.
  22. Saso K., Moehren G., Higashi K., Hoek J. B. Differential inhibition of epidermal growth factor signaling pathways in rat hepatocytes by long-term ethanol treatment // Gastroenterology. 1997. Vol. 112. N 6. P. 2073–2088.
  23. Saso K., Moehren G., Higashi K., Hoek J. B. Differential inhibition of epidermal growth factor signaling pathways in rat hepatocytes by long-term ethanol treatment // Gastroenterology. 1997. Vol. 112. N 6. P. 2073–2088.

Похожие статьи

News

1 October 10:52
A New Issue of Doctor.Ru Internal Medicine, Vol. 21, No. 6 (2022), Published

Find original articles and reviews covering various aspects of сardiology, gastroenterology, internal medicine and the interview with Professor Alexey Nikolaevich Kalyagin

7 July 17:16
A New Issue of Doctor.Ru Neurology Psychiatry, Vol. 21, No. 4 (2022), Published

Find original articles and reviews covering various aspects of neurology, psychiatry and the interview with Professor Alexander Vitalievich Amelin

12 May 11:25
A New Issue of Doctor.Ru Pediatrics, Vol. 21 No. 3 (2022), Published

See the original papers, reviews and clinical cases in headings Pulmonology, Rheumatology, Endocrinology, Neurology, Cross-disciplinary approach and Interview with with an Honoured Scientist of the Sakha (Yakutia) Republic Professor Maria Vasilievna Khandy

4 May 10:02
A New Issue of Doctor.Ru Internal Medicine, Vol. 21, No. 2 (2022), Published

Find original articles and reviews covering various aspects of gastroenterology, internal medicine, rheumatology, endocrinology, special section of postgraduate training and the interview with Professor Dmitry Alexeevich Sychev

18 March 00:00
A New Issue of Doctor.Ru Gynecology, Vol. 21 No. 1 (2022), Published

Find original articles and reviews covering various aspects of obstetrics, perinatology and gynecology, and the interview with Feldberg Dov, MD

All news