Skip to main content
SpringerLink
Log in
Book cover

Alcoholic and Non-Alcoholic Fatty Liver Disease pp 1–20Cite as

Epidemiology and Risk Factors for Alcoholic Liver Disease

  • Chapter

Abstract

Development of liver damage and cirrhosis (ALD) related to alcohol consumption is complex. Studies have reported a threshold of drinking 20–30 g daily for women compared to 40–50 g daily for men. However, the absolute risk of ALD related to heavy drinking is relatively low, ranging from 6 to 15 %, so the majority of drinkers do not develop significant damage. Consuming more than 50 g of alcohol daily can accelerate progression of chronic hepatitis C and genetic hemochromatosis. Prior studies eliminated generalized malnutrition, chronic hepatitis B infection, and the type of alcoholic beverage consumed as risk factors. Obesity is an important risk factor for ALD in heavy drinkers and substantial evidence suggests genetic risks for liver damage in heavy drinkers as well as a genetic risk for drinking heavily (alcohol use disorders). A single-nucleotide polymorphism in PNPLA3 (G allele) is the most important genetic factor associated with an increase in the risk of alcoholic cirrhosis. Risk factors for obesity are also genetically determined, leading to a complex model for understanding the risk of developing ALD. Individual risk factors for ALD are potentially quantifiable within a population and will identify those populations at higher or lower risk for disease related to alcohol consumption. Careful studies of the patterns and levels of consumption of alcoholic beverages in genetically well-characterized populations are needed to understand the complex interaction between genes and the environment in the development of liver injury due to alcohol. Once these results are obtained, sound advice about the risk associated with consumption of alcoholic beverages can be provided to individuals.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Hopewell S, Clarke M, Moher D, Wager E, Middleton P, Altman DG, Schulz KF. CONSORT for reporting randomized controlled trials in journal and conference abstracts: explanation and elaboration. PloS Med. 2008;5, e20.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (Strobe) statement: guidelines for reporting observational studies. Ann Intern Med. 2007;147:573–7.

    Article  Google Scholar 

  3. Oleckno W. Epidemiology: concepts and methods. Long Grove, IL: Waveland Press; 2008.

    Google Scholar 

  4. Rehm J, Samokhvalov AV, Shield KD. Global burden of alcoholic liver diseases. J Hepatol. 2013;59:160–8.

    Article  PubMed  Google Scholar 

  5. World Health Organization. 2014. Global status report on alcohol and health-2014 ed. Geneva, Switzerland: Who Press. http://apps.who.int/iris/bitstream/10665/112736/1/9789240692763_eng.pdf?ua=1. Accessed April 15, 2015.

  6. Bosetti C, Levi F, Lucchini F, Zatonski WA, Negri E, La Vecchia C. Worldwide mortality from cirrhosis: an update to 2002. J Hepatol. 2007;46:827–39.

    Article  PubMed  Google Scholar 

  7. Single E, Robson L, Rehm J, Xie X. Morbidity and mortality attributable to alcohol, tobacco, and illicit drug use in Canada. Am J Public Health. 1999;89:385–90.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Klatskin G. Alcohol and its relation to liver damage. Gastroenterology. 1961;41:443–51.

    CAS  PubMed  Google Scholar 

  9. Baraona E, Lieber CS. Effects of ethanol on lipid metabolism. J Lipid Res. 1979;20:289–315.

    CAS  PubMed  Google Scholar 

  10. Lieber CS, Spritz N. Effects of prolonged ethanol intake in man: role of dietary adipose, and endogenously synthesized fatty acids in the pathogenesis of the alcoholic fatty liver. J Clin Invest. 1966;45:1400–11.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Rubin E, Lieber CS. Alcohol-induced hepatic injury in nonalcoholic volunteers. N Engl J Med. 1968;278:869–76.

    Article  CAS  PubMed  Google Scholar 

  12. Lieber CS, Rubin E. Alcoholic fatty liver in man on a high protein and low fat diet. Am J Med. 1968;44:200–6.

    Article  CAS  PubMed  Google Scholar 

  13. Huetter ML, Fuchs M, Hanle MM, Mason RA, Akinli AS, Imhof A, Kratzer W, Lorenz R, Group ES. Prevalence of risk factors for liver disease in a random population sample in southern Germany. Z Gastroenterol. 2014, 52, 558–63.

    Google Scholar 

  14. Dunn W, Zeng Z, O’neil M, Zhao J, Whitener M, Yu-Jui Wan Y, Mitchell EK, Handler M, Weinman SA. The interaction of rs738409, obesity, and alcohol: a population-based autopsy study. Am J Gastroenterol. 2012;107:1668–74.

    Article  CAS  PubMed  Google Scholar 

  15. Lelbach WK. Cirrhosis in the alcoholic and its relation to the volume of alcohol abuse. Ann N Y Acad Sci. 1975;252:85–105.

    Article  CAS  PubMed  Google Scholar 

  16. Naveau S, Giraud V, Borotto E, Aubert A, Capron F, Chaput JC. Excess weight risk factor for alcoholic liver disease. Hepatology. 1997;25:108–11.

    Article  CAS  PubMed  Google Scholar 

  17. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40:1387–95.

    Article  PubMed  Google Scholar 

  18. Lazo M, Hernaez R, Eberhardt MS, Bonekamp S, Kamel I, Guallar E, Koteish A, Brancati FL, Clark JM. Prevalence of nonalcoholic fatty liver disease in the United States: the Third National Health and Nutrition Examination Survey, 1988-1994. Am J Epidemiol. 2013;178:38–45.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Bellentani S, Tiribelli C. The spectrum of liver disease in the general population: lesson from the Dionysos study. J Hepatol. 2001;35:531–7.

    Article  CAS  PubMed  Google Scholar 

  20. Dunn W, Sanyal AJ, Brunt EM, Unalp-Arida A, Donohue M, Mccullough AJ, Schwimmer JB. Modest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with non-alcoholic fatty liver disease (Nafld). J Hepatol. 2012;57:384–91.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Gunji T, Sato H, Iijima K, Fujibayashi K, Okumura M, Sasabe N, Matsuhashi N. Modest alcohol consumption has an inverse association with liver fat content. Hepatogastroenterology. 2012;59:2552–6.

    CAS  PubMed  Google Scholar 

  22. Moriya A, Iwasaki Y, Ohguchi S, Kayashima E, Mitsumune T, Taniguchi H, Ando M, Yamamoto K. Roles of alcohol consumption in fatty liver: a longitudinal study. J Hepatol. 2015;62(4):921–7.

    Article  CAS  PubMed  Google Scholar 

  23. Howard AA, Arnsten JH, Gourevitch MN. Effect of alcohol consumption on diabetes mellitus: a systematic review. Ann Intern Med. 2004;140:211–9.

    Article  PubMed  Google Scholar 

  24. Rubin E, Lieber CS. Malnutrition and liver disease–an overemphasized relationship. Am J Med. 1968;45:1–6.

    Article  CAS  PubMed  Google Scholar 

  25. Hashimoto Y, Hamaguchi M, Kojima T, Ohshima Y, Ohbora A, Kato T, Nakamura N, Fukui M. The modest alcohol consumption reduces the incidence of fatty liver in men; a population-based large-scale cohort study. J Gastroenterol Hepatol. 2014;30(3):546–52.

    Article  Google Scholar 

  26. Sookoian S, Castano GO, Pirola CJ. Modest alcohol consumption decreases the risk of non-alcoholic fatty liver disease: a meta-analysis of 43 175 individuals. Gut. 2014;63:530–2.

    Article  PubMed  Google Scholar 

  27. Mitchell MC, Herlong HF. Alcohol and nutrition: caloric value, bioenergetics, and relationship to liver damage. Annu Rev Nutr. 1986;6:457–74.

    Article  CAS  PubMed  Google Scholar 

  28. Ramstedt M. Per capita alcohol consumption and liver cirrhosis mortality in 14 European countries. Addiction. 2001;96 Suppl 1:S19–33.

    Article  PubMed  Google Scholar 

  29. Ramstedt M. Alcohol consumption and liver cirrhosis mortality with and without mention of alcohol–the case of Canada. Addiction. 2003;98:1267–76.

    Article  PubMed  Google Scholar 

  30. Becker U, Gronbaek M, Johansen D, Sorensen TI. Lower risk for alcohol-induced cirrhosis in wine drinkers. Hepatology. 2002;35:868–75.

    Article  PubMed  Google Scholar 

  31. Bellentani S, Saccoccio G, Costa G, Tiribelli C, Manenti F, Sodde M, Saveria Croce L, Sasso F, Pozzato G, Cristianini G, Brandi G. Drinking habits as cofactors of risk for alcohol induced liver damage. The Dionysos Study Group. Gut. 1997;41:845–50.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Lu XL, Luo JY, Tao M, Gen Y, Zhao P, Zhao HL, Zhang XD, Dong N. Risk factors for alcoholic liver disease in China. World J Gastroenterol. 2004;10:2423–6.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Fan JG. Epidemiology of alcoholic and nonalcoholic fatty liver disease in China. J Gastroenterol Hepatol. 2013;28 Suppl 1:11–7.

    Article  PubMed  Google Scholar 

  34. Goh GB, Chow WC, Wang R, Yuan JM, Koh WP. Coffee, alcohol and other beverages in relation to cirrhosis mortality: the Singapore Chinese Health Study. Hepatology. 2014;60:661–9.

    Article  PubMed Central  PubMed  Google Scholar 

  35. Becker U, Deis A, Sorensen TI, Gronbaek M, Borch-Johnsen K, Muller CF, Schnohr P, Jensen G. Prediction of risk of liver disease by alcohol intake, sex, and age: a prospective population study. Hepatology. 1996;23:1025–9.

    Article  CAS  PubMed  Google Scholar 

  36. Rehm J, Taylor B, Mohapatra S, Irving H, Baliunas D, Patra J, Roerecke M. Alcohol as a risk factor for liver cirrhosis: a systematic review and meta-analysis. Drug Alcohol Rev. 2010;29:437–45.

    Article  PubMed  Google Scholar 

  37. Mezey E, Kolman CJ, Diehl AM, Mitchell MC, Herlong HF. Alcohol and dietary intake in the development of chronic pancreatitis and liver disease in alcoholism. Am J Clin Nutr. 1988;48:148–51.

    CAS  PubMed  Google Scholar 

  38. Stinson FS, Grant BF, Dufour MC. The critical dimension of ethnicity in liver cirrhosis mortality statistics. Alcohol Clin Exp Res. 2001;25:1181–7.

    Article  CAS  PubMed  Google Scholar 

  39. Corrao G, Ferrari P, Zambon A, Torchio P, Arico S, Decarli A. Trends of liver cirrhosis mortality in Europe, 1970-1989: age-period-cohort analysis and changing alcohol consumption. Int J Epidemiol. 1997;26:100–9.

    Article  CAS  PubMed  Google Scholar 

  40. Barrio E, Tome S, Rodriguez I, Gude F, Sanchez-Leira J, Perez-Becerra E, Gonzalez-Quintela A. Liver disease in heavy drinkers with and without alcohol withdrawal syndrome. Alcohol Clin Exp Res. 2004;28:131–6.

    Article  CAS  PubMed  Google Scholar 

  41. Rotily M, Durbec JP, Berthezene P, Sarles H. Diet and alcohol in liver cirrhosis: a case-control study. Eur J Clin Nutr. 1990;44:595–603.

    CAS  PubMed  Google Scholar 

  42. Mishra L, Sharma S, Potter JJ, Mezey E. More rapid elimination of alcohol in women as compared to their male siblings. Alcohol Clin Exp Res. 1989;13:752–4.

    Article  CAS  PubMed  Google Scholar 

  43. Nanji AA, French SW. Relationship between pork consumption and cirrhosis. Lancet. 1985;1:681–3.

    Article  CAS  PubMed  Google Scholar 

  44. Mcclain CJ, Antonow DR, Cohen DA, Shedlofsky SI. Zinc metabolism in alcoholic liver disease. Alcohol Clin Exp Res. 1986;10:582–9.

    Article  CAS  PubMed  Google Scholar 

  45. Zhong W, Mcclain CJ, Cave M, Kang YJ, Zhou Z. The role of zinc deficiency in alcohol-induced intestinal barrier dysfunction. Am J Physiol Gastrointest Liver Physiol. 2010;298:G625–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Leo MA, Lieber CS. Alcohol, vitamin A, and beta-carotene: adverse interactions, including hepatotoxicity and carcinogenicity. Am J Clin Nutr. 1999;69:1071–85.

    CAS  PubMed  Google Scholar 

  47. Corrao G, Torchio P, Zambon A, D’amicis A, Lepore AR, Di Orio F. Alcohol consumption and micronutrient intake as risk factors for liver cirrhosis: a case-control study. The Provincial Group for the study of Chronic Liver Disease. Ann Epidemiol. 1998;8:154–9.

    Article  CAS  PubMed  Google Scholar 

  48. Berzigotti A, Garcia-Tsao G, Bosch J, Grace ND, Burroughs AK, Morillas R, Escorsell A, Garcia-Pagan JC, Patch D, Matloff DS, Groszmann RJ. Obesity is an independent risk factor for clinical decompensation in patients with cirrhosis. Hepatology. 2011;54:555–61.

    Article  PubMed Central  PubMed  Google Scholar 

  49. Hart CL, Morrison DS, Batty GD, Mitchell RJ, Davey Smith G. Effect of body mass index and alcohol consumption on liver disease: analysis of data from two prospective cohort studies. BMJ. 2010;340:c1240.

    Article  PubMed Central  PubMed  Google Scholar 

  50. Naveau S, Dobrin AS, Balian A, Njike-Nakseu M, Nohra P, Asnacios A, Prevot S, Perlemuter G. Body fat distribution and risk factors for fibrosis in patients with alcoholic liver disease. Alcohol Clin Exp Res. 2013;37:332–8.

    Article  CAS  PubMed  Google Scholar 

  51. Liu B, Balkwill A, Reeves G, Beral V. Body mass index and risk of liver cirrhosis in middle aged Uk women: prospective study. BMJ. 2010;340:c912.

    Article  PubMed Central  PubMed  Google Scholar 

  52. Ruhl CE, Everhart JE. Joint effects of body weight and alcohol on elevated serum alanine aminotransferase in the United States population. Clin Gastroenterol Hepatol. 2005;3:1260–8.

    Article  CAS  PubMed  Google Scholar 

  53. Ekstedt M, Franzen LE, Holmqvist M, Bendtsen P, Mathiesen UL, Bodemar G, Kechagias S. Alcohol consumption is associated with progression of hepatic fibrosis in non-alcoholic fatty liver disease. Scand J Gastroenterol. 2009;44:366–74.

    Article  CAS  PubMed  Google Scholar 

  54. Lesage GD, Baldus WP, Fairbanks VF, Baggenstoss AH, Mccall JT, Moore SB, Taswell HF, Gordon H. Hemochromatosis: genetic or alcohol-induced? Gastroenterology. 1983;84:1471–7.

    CAS  PubMed  Google Scholar 

  55. Rouault TA. Hepatic iron overload in alcoholic liver disease: why does it occur and what is its role in pathogenesis? Alcohol. 2003;30:103–6.

    Article  CAS  PubMed  Google Scholar 

  56. Tavill AS, Qadri AM. Alcohol and iron. Semin Liver Dis. 2004;24:317–25.

    Article  CAS  PubMed  Google Scholar 

  57. 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;27:909–16.

    Article  CAS  PubMed  Google Scholar 

  58. Irving MG, Halliday JW, Powell LW. Association between alcoholism and increased hepatic iron stores. Alcohol Clin Exp Res. 1988;12:7–13.

    Article  CAS  PubMed  Google Scholar 

  59. Ganne-Carrie N, Christidis C, Chastang C, Ziol M, Chapel F, Imbert-Bismut F, Trinchet JC, Guettier C, Beaugrand M. Liver iron is predictive of death in alcoholic cirrhosis: a multivariate study of 229 consecutive patients with alcoholic and/or hepatitis C virus cirrhosis: a prospective follow up study. Gut. 2000;46:277–82.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  60. Fletcher LM, Dixon JL, Purdie DM, Powell LW, Crawford DH. Excess alcohol greatly increases the prevalence of cirrhosis in hereditary hemochromatosis. Gastroenterology. 2002;122:281–9.

    Article  PubMed  Google Scholar 

  61. Adams PC, Agnew S. Alcoholism in hereditary hemochromatosis revisited: prevalence and clinical consequences among homozygous siblings. Hepatology. 1996;23:724–7.

    Article  CAS  PubMed  Google Scholar 

  62. De Feo TM, Fargion S, Duca L, Cesana BM, Boncinelli L, Lozza P, Cappellini MD, Fiorelli G. Non-transferrin-bound iron in alcohol abusers. Alcohol Clin Exp Res. 2001;25:1494–9.

    Article  PubMed  Google Scholar 

  63. Potter BJ, Chapman RW, Nunes RM, Sorrentino D, Sherlock S. Transferrin metabolism in alcoholic liver disease. Hepatology. 1985;5:714–21.

    Article  CAS  PubMed  Google Scholar 

  64. Whitfield JB, Zhu G, Heath AC, Powell L, Martin NG. Effects of alcohol consumption on indices of iron stores and of iron stores on alcohol intake markers. Alcohol Clin Exp Res. 2001;25:1037–45.

    Article  CAS  PubMed  Google Scholar 

  65. Bhattacharya R, Shuhart MC. Hepatitis C and alcohol: interactions, outcomes, and implications. J Clin Gastroenterol. 2003;36:242–52.

    Article  PubMed  Google Scholar 

  66. Harris DR, Gonin R, Alter HJ, Wright EC, Buskell ZJ, Hollinger FB, Seeff LB. The relationship of acute transfusion-associated hepatitis to the development of cirrhosis in the presence of alcohol abuse. Ann Intern Med. 2001;134:120–4.

    Article  CAS  PubMed  Google Scholar 

  67. Ostapowicz G, Watson KJ, Locarnini SA, Desmond PV. Role of alcohol in the progression of liver disease caused by hepatitis C virus infection. Hepatology. 1998;27:1730–5.

    Article  CAS  PubMed  Google Scholar 

  68. Pessione F, Degos F, Marcellin P, Duchatelle V, Njapoum C, Martinot-Peignoux M, Degott C, Valla D, Erlinger S, Rueff B. Effect of alcohol consumption on serum hepatitis C virus RNA and histological lesions in chronic hepatitis C. Hepatology. 1998;27:1717–22.

    Article  CAS  PubMed  Google Scholar 

  69. Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The Obsvirc, Metavir, Clinivir, and Dosvirc groups. Lancet. 1997;349:825–32.

    Article  CAS  PubMed  Google Scholar 

  70. Wiley TE, Mccarthy M, Breidi L, Mccarthy M, Layden TJ. Impact of alcohol on the histological and clinical progression of hepatitis C infection. Hepatology. 1998;28:805–9.

    Article  CAS  PubMed  Google Scholar 

  71. Corrao G, Arico S. Independent and combined action of hepatitis C virus infection and alcohol consumption on the risk of symptomatic liver cirrhosis. Hepatology. 1998;27:914–9.

    Article  CAS  PubMed  Google Scholar 

  72. Mueller S, Millonig G, Seitz HK. Alcoholic liver disease and hepatitis C: a frequently underestimated combination. World J Gastroenterol. 2009;15:3462–71.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  73. Hutchinson SJ, Bird SM, Goldberg DJ. Influence of alcohol on the progression of hepatitis C virus infection: a meta-analysis. Clin Gastroenterol Hepatol. 2005;3:1150–9.

    Article  PubMed  Google Scholar 

  74. American Association for the Study of Liver Diseases and the Infectious Diseases Society of America. 2014. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org/. Accessed April 16, 2015.

  75. Westin J, Lagging LM, Spak F, Aires N, Svensson E, Lindh M, Dhillon AP, Norkrans G, Wejstal R. Moderate alcohol intake increases fibrosis progression in untreated patients with hepatitis C virus infection. J Viral Hepat. 2002;9:235–41.

    Article  PubMed  Google Scholar 

  76. Cheung O, Sterling RK, Salvatori J, Williams K, Hubbard S, Luketic VA, Stravitz TR, Sanyal AJ, Contos MJ, Mills S, Shiffman ML. Mild alcohol consumption is not associated with increased fibrosis in patients with chronic hepatitis C. J Clin Gastroenterol. 2011;45:76–82.

    Article  PubMed  Google Scholar 

  77. Monto A, Patel K, Bostrom A, Pianko S, Pockros P, Mchutchison JG, Wright TL. Risks of a range of alcohol intake on hepatitis C-related fibrosis. Hepatology. 2004;39:826–34.

    Article  PubMed  Google Scholar 

  78. Hrubec Z, Omenn GS. Evidence of genetic predisposition to alcoholic cirrhosis and psychosis: twin concordances for alcoholism and its biological end points by zygosity among male veterans. Alcohol Clin Exp Res. 1981;5:207–15.

    Article  CAS  PubMed  Google Scholar 

  79. Stickel F, Hampe J. Genetic determinants of alcoholic liver disease. Gut. 2012;61:150–9.

    Article  CAS  PubMed  Google Scholar 

  80. Bosron WF, Li TK. Genetic polymorphism of human liver alcohol and aldehyde dehydrogenases, and their relationship to alcohol metabolism and alcoholism. Hepatology. 1986;6:502–10.

    Article  CAS  PubMed  Google Scholar 

  81. Ramchandani VA, Bosron WF, Li TK. Research advances in ethanol metabolism. Pathol Biol (Paris). 2001;49:676–82.

    Article  CAS  Google Scholar 

  82. Thomasson HR, Crabb DW, Edenberg HJ, Li TK, Hwu HG, Chen CC, Yeh EK, Yin SJ. Low frequency of the Adh2*2 allele among Atayal natives of Taiwan with alcohol use disorders. Alcohol Clin Exp Res. 1994;18:640–3.

    Article  CAS  PubMed  Google Scholar 

  83. Borras E, Coutelle C, Rosell A, Fernandez-Muixi F, Broch M, Crosas B, Hjelmqvist L, Lorenzo A, Gutierrez C, Santos M, Szczepanek M, Heilig M, Quattrocchi P, Farres J, Vidal F, Richart C, Mach T, Bogdal J, Jornvall H, Seitz HK, Couzigou P, Pares X. Genetic polymorphism of alcohol dehydrogenase in europeans: the Adh2*2 allele decreases the risk for alcoholism and is associated with Adh3*1. Hepatology. 2000;31:984–9.

    Article  CAS  PubMed  Google Scholar 

  84. Vidal F, Lorenzo A, Auguet T, Olona M, Broch M, Gutierrez C, Aguilar C, Estupina P, Santos M, Richart C. Genetic polymorphisms of Adh2, Adh3, Cyp4502E1 Dra-I and Pst-I, and Aldh2 in Spanish men: lack of association with alcoholism and alcoholic liver disease. J Hepatol. 2004;41:744–50.

    Article  CAS  PubMed  Google Scholar 

  85. Zintzaras E, Stefanidis I, Santos M, Vidal F. Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease? Hepatology. 2006;43:352–61.

    Article  CAS  PubMed  Google Scholar 

  86. Chao YC, Liou SR, Chung YY, Tang HS, Hsu CT, Li TK, Yin SJ. Polymorphism of alcohol and aldehyde dehydrogenase genes and alcoholic cirrhosis in Chinese patients. Hepatology. 1994;19:360–6.

    Article  CAS  PubMed  Google Scholar 

  87. Chao YC, Young TH, Tang HS, Hsu CT. Alcoholism and alcoholic organ damage and genetic polymorphisms of alcohol metabolizing enzymes in Chinese patients. Hepatology. 1997;25:112–7.

    Article  CAS  PubMed  Google Scholar 

  88. Cichoz-Lach H, Partycka J, Nesina I, Celinski K, Slomka M, Wojcierowski J. Alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphism in alcohol liver cirrhosis and alcohol chronic pancreatitis among Polish individuals. Scand J Gastroenterol. 2007;42:493–8.

    Article  CAS  PubMed  Google Scholar 

  89. Tanaka F, Shiratori Y, Yokosuka O, Imazeki F, Tsukada Y, Omata M. Polymorphism of alcohol-metabolizing genes affects drinking behavior and alcoholic liver disease in Japanese men. Alcohol Clin Exp Res. 1997;21:596–601.

    Article  CAS  PubMed  Google Scholar 

  90. Tsutsumi M, Takada A, Wang JS. Genetic polymorphisms of cytochrome P4502E1 related to the development of alcoholic liver disease. Gastroenterology. 1994;107:1430–5.

    Article  CAS  PubMed  Google Scholar 

  91. Carr LG, Hartleroad JY, Liang Y, Mendenhall C, Moritz T, Thomasson H. Polymorphism at the P450iie1 locus is not associated with alcoholic liver disease in Caucasian men. Alcohol Clin Exp Res. 1995;19:182–4.

    Article  CAS  PubMed  Google Scholar 

  92. Iwahashi K, Matsuo Y, Suwaki H, Nakamura K, Ichikawa Y. Cyp2E1 and Aldh2 genotypes and alcohol dependence in Japanese. Alcohol Clin Exp Res. 1995;19:564–6.

    Article  CAS  PubMed  Google Scholar 

  93. Zeng T, Guo FF, Zhang CL, Song FY, Zhao XL, Xie KQ. Roles of cytochrome P4502E1 gene polymorphisms and the risks of alcoholic liver disease: a meta-analysis. PloS One. 2013;8, e54188.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  94. Degoul F, Sutton A, Mansouri A, Cepanec C, Degott C, Fromenty B, Beaugrand M, Valla D, Pessayre D. Homozygosity for alanine in the mitochondrial targeting sequence of superoxide dismutase and risk for severe alcoholic liver disease. Gastroenterology. 2001;120:1468–74.

    Article  CAS  PubMed  Google Scholar 

  95. Martins A, Cortez-Pinto H, Machado M, Goncalves MS, Soren S, Marques-Vidal P, De Moura MC, Camilo ME. Are genetic polymorphisms of tumour necrosis factor alpha, interleukin-10, Cd14 endotoxin receptor or manganese superoxide dismutase associated with alcoholic liver disease? Eur J Gastroenterol Hepatol. 2005;17:1099–104.

    Article  CAS  PubMed  Google Scholar 

  96. Stewart SF, Leathart JB, Chen Y, Daly AK, Rolla R, Vay D, Mottaran E, Vidali M, Albano E, Day CP. Valine-alanine manganese superoxide dismutase polymorphism is not associated with alcohol-induced oxidative stress or liver fibrosis. Hepatology. 2002;36:1355–60.

    Article  CAS  PubMed  Google Scholar 

  97. Campos J, Gonzalez-Quintela A, Quinteiro C, Gude F, Perez LF, Torre JA, Vidal C. The -159C/T polymorphism in the promoter region of the Cd14 gene is associated with advanced liver disease and higher serum levels of acute-phase proteins in heavy drinkers. Alcohol Clin Exp Res. 2005;29:1206–13.

    Article  CAS  PubMed  Google Scholar 

  98. Jarvelainen HA, Orpana A, Perola M, Savolainen VT, Karhunen PJ, Lindros KO. Promoter polymorphism of the Cd14 endotoxin receptor gene as a risk factor for alcoholic liver disease. Hepatology. 2001;33:1148–53.

    Article  CAS  PubMed  Google Scholar 

  99. Meiler C, Muhlbauer M, Johann M, Hartmann A, Schnabl B, Wodarz N, Schmitz G, Scholmerich J, Hellerbrand C. Different effects of a Cd14 gene polymorphism on disease outcome in patients with alcoholic liver disease and chronic hepatitis C infection. World J Gastroenterol. 2005;11:6031–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  100. Petrasek J, Hubacek JA, Stickel F, Sperl J, Berg T, Ruf E, Wichmann HE, Pfeufer A, Meitinger T, Trunecka P, Spicak J, Jirsa M. Do common genetic variants in endotoxin signaling pathway contribute to predisposition to alcoholic liver cirrhosis? Clin Chem Lab Med. 2009;47:398–404.

    Article  CAS  PubMed  Google Scholar 

  101. Zeng T, Zhang CL, Han XY, Zhao S, Xie KQ. Association between Cd14-159C > T polymorphisms and the risk for alcoholic liver disease: a meta-analysis. Eur J Gastroenterol Hepatol. 2013;25:1183–9.

    CAS  PubMed  Google Scholar 

  102. Bathgate AJ, Pravica V, Perrey C, Hayes PC, Hutchinson IV. Polymorphisms in tumour necrosis factor alpha, interleukin-10 and transforming growth factor beta1 genes and end-stage liver disease. Eur J Gastroenterol Hepatol. 2000;12:1329–33.

    Article  CAS  PubMed  Google Scholar 

  103. Grove J, Daly AK, Bassendine MF, Gilvarry E, Day CP. Interleukin 10 promoter region polymorphisms and susceptibility to advanced alcoholic liver disease. Gut. 2000;46:540–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  104. Marcos M, Pastor I, Gonzalez-Sarmiento R, Laso FJ. Interleukin-10 gene polymorphism is associated with alcoholism but not with alcoholic liver disease. Alcohol Alcohol. 2008;43:523–8.

    Article  CAS  PubMed  Google Scholar 

  105. Grove J, Daly AK, Bassendine MF, Day CP. Association of a tumor necrosis factor promoter polymorphism with susceptibility to alcoholic steatohepatitis. Hepatology. 1997;26:143–6.

    Article  CAS  PubMed  Google Scholar 

  106. Marcos M, Gomez-Munuera M, Pastor I, Gonzalez-Sarmiento R, Laso FJ. Tumor necrosis factor polymorphisms and alcoholic liver disease: a huge review and meta-analysis. Am J Epidemiol. 2009;170:948–56.

    Article  PubMed  Google Scholar 

  107. 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;13:267–76.

    Article  CAS  PubMed  Google Scholar 

  108. Takamatsu M, Yamauchi M, Maezawa Y, Saito S, Maeyama S, Uchikoshi T. Genetic polymorphisms of interleukin-1beta in association with the development of alcoholic liver disease in Japanese patients. Am J Gastroenterol. 2000;95:1305–11.

    CAS  PubMed  Google Scholar 

  109. Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, Boerwinkle E, Cohen JC, Hobbs HH. Genetic variation in Pnpla3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40:1461–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  110. Yuan X, Waterworth D, Perry JR, Lim N, Song K, Chambers JC, Zhang W, Vollenweider P, Stirnadel H, Johnson T, Bergmann S, Beckmann ND, Li Y, Ferrucci L, Melzer D, Hernandez D, Singleton A, Scott J, Elliott P, Waeber G, Cardon L, Frayling TM, Kooner JS, Mooser V. Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes. Am J Hum Genet. 2008;83:520–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  111. Kozlitina J, Smagris E, Stender S, Nordestgaard BG, Zhou HH, Tybjaerg-Hansen A, Vogt TF, Hobbs HH, Cohen JC. Exome-wide association study identifies a Tm6sf2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2014;46:352–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  112. He S, Mcphaul C, Li JZ, Garuti R, Kinch L, Grishin NV, Cohen JC, Hobbs HH. A sequence variation (I148M) in Pnpla3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis. J Biol Chem. 2010;285:6706–15.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  113. Pingitore P, Pirazzi C, Mancina RM, Motta BM, Indiveri C, Pujia A, Montalcini T, Hedfalk K, Romeo S. Recombinant Pnpla3 protein shows triglyceride hydrolase activity and its I148M mutation results in loss of function. Biochim Biophys Acta. 2014;1841:574–80.

    Article  CAS  PubMed  Google Scholar 

  114. Winberg ME, Motlagh MK, Stenkula KG, Holm C, Jones HA. Adiponutrin: a multimeric plasma protein. Biochem Biophys Res Commun. 2014;446:1114–9.

    Article  CAS  PubMed  Google Scholar 

  115. Tian C, Stokowski RP, Kershenobich D, Ballinger DG, Hinds DA. Variant in Pnpla3 is associated with alcoholic liver disease. Nat Genet. 2010;42:21–3.

    Article  CAS  PubMed  Google Scholar 

  116. Stickel F, Buch S, Lau K, Meyer Zu Schwabedissen H, Berg T, Ridinger M, Rietschel M, Schafmayer C, Braun F, Hinrichsen H, Gunther R, Arlt A, Seeger M, Muller S, Seitz HK, Soyka M, Lerch M, Lammert F, Sarrazin C, Kubitz R, Haussinger D, Hellerbrand C, Broring D, Schreiber S, Kiefer F, Spanagel R, Mann K, Datz C, Krawczak M, Wodarz N, Volzke H, Hampe J. Genetic variation in the Pnpla3 gene is associated with alcoholic liver injury in caucasians. Hepatology. 2011;53:86–95.

    Article  CAS  PubMed  Google Scholar 

  117. Trepo E, Gustot T, Degre D, Lemmers A, Verset L, Demetter P, Ouziel R, Quertinmont E, Vercruysse V, Amininejad L, Deltenre P, Le Moine O, Deviere J, Franchimont D, Moreno C. Common polymorphism in the Pnpla3/adiponutrin gene confers higher risk of cirrhosis and liver damage in alcoholic liver disease. J Hepatol. 2011;55:906–12.

    Article  CAS  PubMed  Google Scholar 

  118. Chamorro AJ, Torres JL, Miron-Canelo JA, Gonzalez-Sarmiento R, Laso FJ, Marcos M. Systematic review with meta-analysis: the I148M variant of patatin-like phospholipase domain-containing 3 gene (Pnpla3) is significantly associated with alcoholic liver cirrhosis. Aliment Pharmacol Ther. 2014;40:571–81.

    Article  CAS  PubMed  Google Scholar 

  119. Rose G. Sick individuals and sick populations. Int J Epidemiol. 2001;30:427–32. discussion 433–4.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of General Internal Medicine, Johns Hopkins Hospital, 2024 East Monument Street, Suite 2-600, Baltimore, MD, 21205, USA

    Mariana Lazo M.D., Ph.D., Sc.M.

  2. Department of Internal Medicine, U.T. Southwestern Medical Center, 5323 Harry Hines Boulevard, Room G5.240, Dallas, Texas, 75390, USA

    Mack C. Mitchell M.D.

Authors
  1. Mariana Lazo M.D., Ph.D., Sc.M.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mack C. Mitchell M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mack C. Mitchell M.D. .

Editor information

Editors and Affiliations

  1. Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA

    Naga Chalasani

  2. Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Gyongyi Szabo

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Lazo, M., Mitchell, M.C. (2016). Epidemiology and Risk Factors for Alcoholic Liver Disease. In: Chalasani, N., Szabo, G. (eds) Alcoholic and Non-Alcoholic Fatty Liver Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-20538-0_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-20538-0_1

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-20537-3

  • Online ISBN: 978-3-319-20538-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation