Advertisement

Liver Diseases pp 285-292 | Cite as

Alcoholic Liver Disease

  • Vatsalya VatsalyaEmail author
  • Hamza Zahid Hassan
Chapter

Abstract

Alcoholic liver disease (ALD) is the most widespread form of chronic liver disease that progresses from alcoholic steatosis/fatty liver (AFL) to alcoholic steatohepatitis (ASH). Heavy, and prolonged binge type of alcohol drinking would generally lead to AFL that develops into fibrosis and further manifests as clinically significant conditions namely alcoholic cirrhosis (AC, as a late stage ALD) and infrequently to hepatocellular carcinoma (HCC). Acutely progressed form of ALD is identified as alcoholic hepatitis (AH) that shows rapid development of liver pathology, immune dysregulation and exhibits high mortality as prognosis. Acute-on-chronic liver failure (ACLF - an advanced form of ALD) is observed in patients who exhibit acute decompensation along with underlying AC. ALD patients are often diagnosed at progressed and severe stages and very few studies have characterized early onset of ALD. Diagnosis of ALD requires thorough documentation of chronic heavy alcohol intake, and differential diagnosis to rule out other forms of liver condition. Progression of AFL into different liver conditions involves the interplay of several pathways that could precede/overlap each other at different stages and conditions. Multiple pathological pathways are involved in progression and severity of ALD. Predominant mechanisms involved in the ALD pathology are oxidative stress, dysregulated metabolism of nutritional constituents and malnutrition, genetics and epigenetics factors, ER stress, gut permeability and gut-derived liver toxicity and inflammation. Medical management of severe and progressed form of ALD includes treatment associated with complications, reduction of alcohol withdrawal syndrome, prevention and treatment of infections, nutritional supplementation, and strategies for lowering of alcohol consumption. With no specific treatment approved by the FDA for any stage of ALD, extended abstinence from alcohol has so far been the best interventional strategy to prevent disease progression.

Keywords

Alcohol Alcohol dehydrogenase Alcoholic liver disease Alcoholic cirrhosis Alcoholic hepatitis Epigenetics Genetics Gut-derived liver injury Malnutrition Oxidative stress 

References

  1. 1.
    Singal AK, Bataller R, Ahn J, Kamath PS, Shah VH. ACG Clinical Guideline: alcoholic liver disease. Am J Gastroenterol. 2018;113(2):175.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Vatsalya V, Song M, Schwandt ML, Cave MC, Barve SS, George DT, et al. Effects of sex, drinking history, and omega-3 and omega-6 fatty acids dysregulation on the onset of liver injury in very heavy drinking alcohol-dependent patients. Alcohol Clin Exp Res. 2016;40(10):2085–93.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Seitz HK, Bataller R, Cortez-Pinto H, Gao B, Gual A, Lackner C, et al. Alcoholic liver disease. Nat Rev Dis Primers. 2018;4(1):16.PubMedCrossRefGoogle Scholar
  4. 4.
    Marsano LS, Vatsalya V, Hassan A, McClain CJ. Clinical features, disease modifiers, and natural history of alcoholic liver disease. In: Alcoholic and non-alcoholic fatty liver disease. New York: Springer; 2016. p. 165–82.CrossRefGoogle Scholar
  5. 5.
    Vatsalya V, Bin Liaquat H, Ghosh K, Prakash Mokshagundam S, J McClain C. A review on the sex differences in organ and system pathology with alcohol drinking. Curr Drug Abuse Rev. 2016;9(2):87–92.PubMedCrossRefGoogle Scholar
  6. 6.
    Kharbanda KK, Ronis MJ, Shearn CT, Petersen DR, Zakhari S, Warner DR, et al. Role of nutrition in alcoholic liver disease: summary of the symposium at the ESBRA 2017 congress. Biomolecules. 2018;8(2):16.PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Warner DR, Liu H, Miller ME, Ramsden CE, Gao B, Feldstein AE, et al. Dietary linoleic acid and its oxidized metabolites exacerbate liver injury caused by ethanol via induction of hepatic proinflammatory response in mice. Am J Pathol. 2017;187(10):2232–45.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    McClain C, Vatsalya V, Cave M. Role of zinc in the development/progression of alcoholic liver disease. Curr Treat Options Gastroenterol. 2017;15(2):285–95.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Vatsalya V, Kong M, Cave MC, Liu N, Schwandt ML, George DT, et al. Association of serum zinc with markers of liver injury in very heavy drinking alcohol dependent patients. J Nutr Biochem. 2018;59:49–55.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Vatsalya V, Cave M, Barve S, Ramchandani VA, McClain CJ, editors. Role of serum zinc and polyunsaturated fatty acids in the exacerbation of liver injury in treatment naive HIV-infected alcohol dependent patients. Hepatology. Hoboken, NJ: Wiley; 2017.Google Scholar
  11. 11.
    Moghe A, Ghare S, Lamoreau B, Mohammad M, Barve S, McClain C, et al. Molecular mechanisms of acrolein toxicity: relevance to human disease. Toxicol Sci. 2015;143(2):242–55.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Lu Y, Cederbaum AI. Cytochrome P450s and alcoholic liver disease. Curr Pharm Des. 2018;24(14):1502–17.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Vatsalya V, Kong M, Gobejishvili L, Chen W-Y, Srivastava S, Barve S, et al. Urinary acrolein metabolite levels in severe acute alcoholic hepatitis patients. Am J Physiol Gastrointest Liver Physiol. 2019;316(1):G115–22.PubMedCrossRefGoogle Scholar
  14. 14.
    Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest. 2004;114(2):147–52.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Zeng T, Zhang C-L, Xiao M, Yang R, Xie K-Q. Critical roles of Kupffer cells in the pathogenesis of alcoholic liver disease: from basic science to clinical trials. Front Immunol. 2016;7:538.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Loomba R, Schork N, Chen C-H, Bettencourt R, Bhatt A, Ang B, et al. Heritability of hepatic fibrosis and steatosis based on a prospective twin study. Gastroenterology. 2015;149(7):1784–93.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Stickel F, Hampe J. Genetic determinants of alcoholic liver disease. Gut. 2012;61(1):150–9.PubMedCrossRefGoogle Scholar
  18. 18.
    He L, Deng T, Luo HS. Genetic polymorphism in alcohol dehydrogenase 2 (ADH2) gene and alcoholic liver cirrhosis risk. Int J Clin Exp Med. 2015;8(5):7786–93.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Szabo G. Gut–liver axis in alcoholic liver disease. Gastroenterology. 2015;148(1):30–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Bala S, Marcos M, Gattu A, Catalano D, Szabo G. Acute binge drinking increases serum endotoxin and bacterial DNA levels in healthy individuals. PLoS One. 2014;9(5):e96864.PubMedPubMedCentralCrossRefGoogle Scholar

Further Reading and Additional Resources

  1. Adachi Y, Moore LE, Bradford BU, Gao W, Thurman RG. Antibiotics prevent liver injury in rats following long-term exposure to ethanol. Gastroenterology. 1995;108(1):218–24.PubMedCrossRefGoogle Scholar
  2. Beier JI, Arteel GE, McClain CJ. Advances in alcoholic liver disease. Curr Gastroenterol Rep. 2011;13(1):56–64.  https://doi.org/10.1007/s11894-010-0157-5.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bezkorovainy A. Probiotics: determinants of survival and growth in the gut. Am J Clin Nutr. 2001;73(2 Suppl):399S–405S.PubMedCrossRefGoogle Scholar
  4. Blasbalg TL, Hibbeln JR, Ramsden CE, Majchrzak SF, Rawlings RR. Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the twentieth century. Am J Clin Nutr. 2011;93(5):950–62.  https://doi.org/10.3945/ajcn.110.006643.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Broitman SA, Gottlieb LS, Zamcheck N. Influence of neomycin and ingested endotoxin in the pathogenesis of choline deficiency cirrhosis in the adult rat. J Exp Med. 1964;119:633–42.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest. 2004;114(2):147–52.  https://doi.org/10.1172/jci200422422.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest. 2004;114(2):147–52.  https://doi.org/10.1172/JCI22422.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Cederbaum AI, Lu Y, Wu D. Role of oxidative stress in alcohol-induced liver injury. Arch Toxicol. 2009;83(6):519–48.  https://doi.org/10.1007/s00204-009-0432-0.CrossRefPubMedGoogle Scholar
  9. Chapman RW, Morgan MY, Laulicht M, Hoffbrand AV, Sherlock S. Hepatic iron stores and markers of iron overload in alcoholics and patients with idiopathic hemochromatosis. Dig Dis Sci. 1982;27(10):909–16.PubMedCrossRefGoogle Scholar
  10. Das SK, Vasudevan DM. Alcohol-induced oxidative stress. Life Sci. 2007;81(3):177–87.  https://doi.org/10.1016/j.lfs.2007.05.005.CrossRefPubMedGoogle Scholar
  11. Donohue TM Jr, Tuma DJ, Sorrell MF. Binding of metabolically derived acetaldehyde to hepatic proteins in vitro. Lab Investig. 1983;49(2):226–9.PubMedGoogle Scholar
  12. Fletcher LM, Powell LW. Hemochromatosis and alcoholic liver disease. Alcohol. 2003;30(2):131–6.PubMedCrossRefGoogle Scholar
  13. Fooks LJ, Gibson GR. Probiotics as modulators of the gut flora. Br J Nutr. 2002;88(Suppl 1):S39–49.  https://doi.org/10.1079/BJN2002628.CrossRefPubMedGoogle Scholar
  14. Fu S, Yang L, Li P, Hofmann O, Dicker L, Hide W, et al. Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity. Nature. 2011;473(7348):528–31.  https://doi.org/10.1038/nature09968.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Gabuzda GJ. Hepatic coma: clinical considerations, pathogenesis, and management. Adv Intern Med. 1962;11:11–73.PubMedGoogle Scholar
  16. Gao B, Seki E, Brenner DA, Friedman S, Cohen JI, Nagy L, et al. Innate immunity in alcoholic liver disease. Am J Physiol Gastrointest Liver Physiol. 2011;300(4):G516–25.  https://doi.org/10.1152/ajpgi.00537.2010.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Gustot T, Lemmers A, Moreno C, Nagy N, Quertinmont E, Nicaise C, et al. Differential liver sensitization to toll-like receptor pathways in mice with alcoholic fatty liver. Hepatology. 2006;43(5):989–1000.  https://doi.org/10.1002/hep.21138.CrossRefPubMedGoogle Scholar
  18. He L, Deng T, Luo HS. Genetic polymorphism in alcohol dehydrogenase 2 (ADH2) gene and alcoholic liver cirrhosis risk. Int J Clin Exp Med. 2015;8(5):7786–93.PubMedPubMedCentralGoogle Scholar
  19. Honchel R, Ray MB, Marsano L, Cohen D, Lee E, Shedlofsky S, McClain CJ. Tumor necrosis factor in alcohol enhanced endotoxin liver injury. Alcohol Clin Exp Res. 1992;16(4):665–9.PubMedCrossRefGoogle Scholar
  20. Iimuro Y, Gallucci RM, Luster MI, Kono H, Thurman RG. Antibodies to tumor necrosis factor alfa attenuate hepatic necrosis and inflammation caused by chronic exposure to ethanol in the rat. Hepatology. 1997;26(6):1530–7.  https://doi.org/10.1002/hep.510260621.CrossRefPubMedGoogle Scholar
  21. Ji C. Dissection of endoplasmic reticulum stress signaling in alcoholic and non-alcoholic liver injury. J Gastroenterol Hepatol. 2008;23(Suppl 1):S16–24.  https://doi.org/10.1111/j.1440-1746.2007.05276.x.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Ji C. Mechanisms of alcohol-induced endoplasmic reticulum stress and organ injuries. Biochem Res Int. 2012;  https://doi.org/10.1155/2012/216450.CrossRefGoogle Scholar
  23. Ji C, Kaplowitz N. Betaine decreases hyperhomocysteinemia, endoplasmic reticulum stress, and liver injury in alcohol-fed mice. Gastroenterology. 2003;124(5):1488–99.PubMedCrossRefGoogle Scholar
  24. Keshavarzian A, Choudhary S, Holmes EW, Yong S, Banan A, Jakate S, Fields JZ. Preventing gut leakiness by oats supplementation ameliorates alcohol-induced liver damage in rats. J Pharmacol Exp Ther. 2001;299(2):442–8.PubMedGoogle Scholar
  25. Khoruts A, Stahnke L, McClain CJ, Logan G, Allen JI. Circulating tumor necrosis factor, interleukin-1, and interleukin-6 concentrations in chronic alcoholic patients. Hepatology. 1991;13(2):267–76.PubMedCrossRefGoogle Scholar
  26. Luckey TD, Reyniers JA, Gyorgy P, Forbes M. Germfree animals and liver necrosis. Ann N Y Acad Sci. 1954;57(6):932–5.PubMedCrossRefGoogle Scholar
  27. Madigan MT. Chapter 12: Prokaryotic diversity: the bacteria chapter. In: Martinko JM, editor. Brock biology of microorganisms. 11th ed. Upper Saddle River, NJ: Pearson Prentice Hall; 2006.Google Scholar
  28. Malhi H, Kaufman RJ. Endoplasmic reticulum stress in liver disease. J Hepatol. 2011;54(4):795–809.  https://doi.org/10.1016/j.jhep.2010.11.005.CrossRefPubMedGoogle Scholar
  29. Mandrekar P. Epigenetic regulation in alcoholic liver disease. World J Gastroenterol: WJG. 2011;17(20):2456.PubMedCrossRefGoogle Scholar
  30. McClain CJ, Cohen DA. Increased tumor necrosis factor production by monocytes in alcoholic hepatitis. Hepatology. 1989;9(3):349–51.PubMedCrossRefGoogle Scholar
  31. McClain CJ, Zieve L. Portal-systemic encephalopathy: recognition and variations. In: Davidson CS, editor. Problems in liver diseases. New York: Stratton Intercontinental Medical Book Corp.; 1979. p. 162–72.Google Scholar
  32. McClain CJ, Barve SS, Barve A, Marsano L. Alcoholic liver disease and malnutrition. Alcohol Clin Exp Res. 2011;35(5):815–20.  https://doi.org/10.1111/j.1530-0277.2010.01405.x.CrossRefPubMedPubMedCentralGoogle Scholar
  33. McClain CJ, Song Z, Barve SS, Hill DB, Deaciuc I. Recent advances in alcoholic liver disease. IV. Dysregulated cytokine metabolism in alcoholic liver disease. Am J Physiol Gastrointest Liver Physiol. 2004;287(3):G497–502.  https://doi.org/10.1152/ajpgi.00171.2004.CrossRefPubMedGoogle Scholar
  34. Mendenhall CL, Anderson S, Weesner RE, Goldberg SJ, Crolic KA. Protein-calorie malnutrition associated with alcoholic hepatitis. Veterans Administration Cooperative Study Group on Alcoholic Hepatitis. Am J Med. 1984;76(2):211–22.PubMedCrossRefGoogle Scholar
  35. Mendenhall CL, Moritz TE, Roselle GA, Morgan TR, Nemchausky BA, Tamburro CH, et al. Protein-energy malnutrition in severe alcoholic hepatitis: diagnosis and response to treatment. The VA Cooperative Study Group #275. JPEN J Parenter Enteral Nutr. 1995;19(4):258–65.PubMedCrossRefGoogle Scholar
  36. Mendenhall CL, Tosch T, Weesner RE, Garcia-Pont P, Goldberg SJ, Kiernan T, et al. VA cooperative study on alcoholic hepatitis. II: Prognostic significance of protein-calorie malnutrition. Am J Clin Nutr. 1986;43(2):213–8.PubMedCrossRefGoogle Scholar
  37. Mendenhall C, Roselle GA, Gartside P, Moritz T. Relationship of protein calorie malnutrition to alcoholic liver disease: a reexamination of data from two Veterans Administration Cooperative Studies. Alcohol Clin Exp Res. 1995;19(3):635–41.PubMedCrossRefGoogle Scholar
  38. Nanji AA, French SW. Dietary linoleic acid is required for the development of experimentally induced alcoholic liver injury. Life Sci. 1989;44(3):223–7.PubMedCrossRefGoogle Scholar
  39. Nanji AA, Jokelainen K, Tipoe GL, Rahemtulla A, Dannenberg AJ. Dietary saturated fatty acids reverse inflammatory and fibrotic changes in rat liver despite continued ethanol administration. J Pharmacol Exp Ther. 2001;299(2):638–44.PubMedGoogle Scholar
  40. Nanji AA, Khettry U, Sadrzadeh SM. Lactobacillus feeding reduces endotoxemia and severity of experimental alcoholic liver (disease). Proc Soc Exp Biol Med. 1994;205(3):243–7.PubMedCrossRefGoogle Scholar
  41. Nanji AA, Yang EK, Fogt F, Sadrzadeh SM, Dannenberg AJ. Medium chain triglycerides and vitamin E reduce the severity of established experimental alcoholic liver disease. J Pharmacol Exp Ther. 1996;277(3):1694–700.PubMedGoogle Scholar
  42. Nolan JP. The contribution of gut-derived endotoxins to liver injury. Yale J Biol Med. 1979;52(1):127–33.PubMedPubMedCentralGoogle Scholar
  43. Purohit V, Bode JC, Bode C, Brenner DA, Choudhry MA, Hamilton F, et al. Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: summary of a symposium. Alcohol. 2008;42(5):349–61.  https://doi.org/10.1016/j.alcohol.2008.03.131.CrossRefPubMedPubMedCentralGoogle Scholar
  44. Rutenburg AM, Sonnenblick E, Koven I, Aprahamian HA, Reiner L, Fine J. The role of intestinal bacteria in the development of dietary cirrhosis in rats. J Exp Med. 1957;106(1):1–14.PubMedPubMedCentralCrossRefGoogle Scholar
  45. Sakhuja P. Pathology of alcoholic liver disease, can it be differentiated from nonalcoholic steatohepatitis? World J Gastroenterol. 2014;20(44):16474–9.  https://doi.org/10.3748/wjg.v20.i44.16474.CrossRefPubMedPubMedCentralGoogle Scholar
  46. Setshedi M, Wands JR, Monte SM. Acetaldehyde adducts in alcoholic liver disease. Oxidative Med Cell Longev. 2010;3(3):178–85.  https://doi.org/10.4161/oxim.3.3.12288.CrossRefGoogle Scholar
  47. Siebler J, Galle PR, Weber MM. The gut-liver-axis: endotoxemia, inflammation, insulin resistance, and NASH. J Hepatol. 2008;48(6):1032–4.  https://doi.org/10.1016/j.jhep.2008.03.007.CrossRefPubMedGoogle Scholar
  48. Stickel F, Hampe J. Genetic determinants of alcoholic liver disease. Gut. 2012;61(1):150–9.  https://doi.org/10.1136/gutjnl-2011-301239.CrossRefPubMedGoogle Scholar
  49. Szabo G, Bala S. Alcoholic liver disease and the gut-liver axis. World J Gastroenterol. 2010;16(11):1321–9.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Tsutsumi M, Takada A, Wang JS. Genetic polymorphisms of cytochrome P4502E1 related to the development of the alcoholic liver disease. Gastroenterology. 1994;107(5):1430–5.PubMedCrossRefGoogle Scholar
  51. Warner DR, Liu H, Miller ME, Ramsden CE, Gao B, Feldstein AE, et al. Dietary linoleic acid and its oxidized metabolites exacerbate liver injury caused by ethanol via induction of hepatic proinflammatory response in mice. Am J Pathol. 2017;187(10):2232–45.  https://doi.org/10.1016/j.ajpath.2017.06.008.CrossRefPubMedPubMedCentralGoogle Scholar
  52. Zeng T, Zhang CL, Xiao M, Yang R, Xie KQ. Critical roles of Kupffer cells in the pathogenesis of alcoholic liver disease: from basic science to clinical trials. Front Immunol. 2016;7  https://doi.org/10.3389/fimmu.2016.00538.
  53. Zhao HY, Wang HJ, Lu Z, Xu SZ. Intestinal microflora in patients with liver cirrhosis. Chin J Dig Dis. 2004;5(2):64–7.PubMedCrossRefGoogle Scholar
  54. Zieve L. Pathogenesis of hepatic coma. Arch Intern Med. 1966;118(3):211–23.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Division of Gastroenterology, Hepatology, and Nutrition, Department of MedicineUniversity of LouisvilleLouisvilleUSA
  2. 2.Robley Rex VA Medical CenterLouisvilleUSA

Personalised recommendations