Advertisement

Wiener Medizinische Wochenschrift

, Volume 156, Issue 19–20, pp 523–526 | Cite as

Liver, Alcohol and Gender

  • Christian MüllerEmail author
Themenschwerpunkt

Summary

Gender differences in alcohol-induced liver injury have been well described. Females develop alcoholic liver injury more rapidly and have a lower alcohol toxic threshold than men. The mechanism for this difference is poorly characterized, differences in first-pass metabolism in the stomach, or elimination rate, or alcohol distribution volume in the body have been suggested. In addition, estrogen has a major influence on the susceptibility of Kupffer cells to gut-derived LPS resulting in increased proinflammatory cytokine production, which could be a major contributing factor to the increased risk of women to alcohol-induced liver disease.

Keywords

Alcohol consumption Females Alcoholic liver disease Gender 

Geschlechterspezifische Besonderheiten des Einflusses von Alkohol auf die Leber

Zusammenfassung

Geschlechtsspezifische Unterschiede in der Empfindlichkeit gegenüber alkohol-induzierten Leberschädigungen sind wohl bekannt. Frauen entwickeln alkoholische Lebererkrankungen schneller als Männer und weisen einen niedrigeren alkohol-toxischen Schwellenwert auf. Die pathophysiologischen Ursachen für diese Unterschiede sind jedoch nur unzureichend charakterisiert und liegen in einem unterschiedlichen first-pass-Metabolismus des Alkohols im Magen, unterschiedlicher Alkohol-Eliminationsrate und unterschiedlichem Alkohol-Verteilvolumen im Körper. Zusätzlich scheint der hormonelle Einfluss von Östrogen eine wesentliche Rolle zu spielen: Östrogen steigerte die Empfindlichkeit der Kupferzellen in der Leber gegenüber Lipopolysaccharid (LPS), das aus dem Darm über das Pfortadersystem zur Leber transportiert wird, und damit die Produktion von proinflammatorischen Zytokinen. Diese Mechanismen werden heute als die ursächlich wahrscheinlichsten für die erhöhte Empfindlichkeit der Leber von Frauen gegenüber den schädlichen Einflüssen des Alkohols angesehen.

Schlüsselwörter

Alkoholkonsum Frauen Alkoholinduzierte Leberkrankung Gender 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ashley MJ, Olin JS, le Riche WH, Kornaczewski A, Schmidt W, Rankin JG (1977) Morbidity in alcoholics: evidence for accelerated development of physiological disease in woman. Arch Intern Med 137: 883–887PubMedCrossRefGoogle Scholar
  2. Krasner N, Davis M, Portmann B, Williams R (1977) Changing pattern of alcoholic liver disease in Great Britain: Relation to sex and signs of autoimmunity. BMJ 1: 1497–1500PubMedGoogle Scholar
  3. Morgan MY, Sherlock S (1977) Sex-related differences among 100 patients with alcoholic liver disease. BMJ 1: 939–941PubMedGoogle Scholar
  4. Saunders JB, Davis M, Williams R (1981) Do women develop alcoholic liver disease more readily than men? BMJ 282: 1140–1143PubMedGoogle Scholar
  5. Norton R, Batey R, Dwyer T, MacMahon S (1987) Alcohol consumption and the risk of alcohol related cirrhosis in women. BMJ 295: 80–82PubMedGoogle Scholar
  6. Adachi Y, Bradford GU, Gao W, Bojes H, Thurman RG (1994) Inactivation of Kupffer cells prevents early alcohol-induced liver injury. Hepatology 20: 453–560PubMedCrossRefGoogle Scholar
  7. Ikejma K, Enomoto N, Iimuro Y, Ikejima A, Fang D, Xu J, Forman DT, Brenner DA, Thurman RG (1998) Estrogen increases sensitivity of hepatic Kupffer cells to endotoxin. Am J Physiol 274: G669–G676Google Scholar
  8. Wilsnack SC, Wilsnack RW (2002) International gender and alcohol research: recent findings and future directions. Alcohol Res Health 26: 245–250PubMedGoogle Scholar
  9. Hoffmeister H, Schelp FP, Mensink GBM, Dietz E, Böhning D (1999) The relationship between alcohol consumption, health indicators and mortality in the German population. Int J Epidemiol 28: 1066–1072PubMedCrossRefGoogle Scholar
  10. Bellentani S, Tiribelli C, Saccoccio G, Sodde M, Fratti N, De Martin C, Cristianini G (1994) Prevalence of chronic liver disease in the general population of northern Italy: the Dionysos study. Hepatology 20: 1442–1449PubMedCrossRefGoogle Scholar
  11. Wilsnack RW, Vogeltanz ND, Wilsnack SC, Harris TR, Ahlstrom S, Bondy S, Csemy L, Ferrence R, Ferris J, Fleming J, Graham K, Greenfield T, Guyon L, Haavio-Mannila E, Kellner F, Knibbe R, Kubicka L, Loukomskaia M, Mustonen H, Nadeau L, Narusk A, Neve R, Rahav G, Spak F, Teichman M, Trocki K, Webster I, Weiss S (2000) Gender differences in alcohol consumption and adverse drinking consequences: cross-cultural patterns. Addiction 95: 251–265PubMedCrossRefGoogle Scholar
  12. Becker U, Dies A, Sorensen TIA, Gronbaeck M, Borch-Johnsen K, Müller CF, Schnohr P, Jensen G (1996) Prediction of risk of liver disease by alcohol intake, sex, and age: a prospective population study. Hepatology 23: 1025–1029PubMedCrossRefGoogle Scholar
  13. Rehm J, Rehn N, Room R, Monteiro M, Gmel G, Jernigan D, Frick U (2003) The global distribution of average volume of alcohol consumption and patterns of drinking. Eur Addict Res 9: 147–156PubMedCrossRefGoogle Scholar
  14. Mandayam S, Jamal MM, Morgan TR (2004) Epidemiology of alcoholic liver disease. Sem Liv Dis 24: 217–232CrossRefGoogle Scholar
  15. Lelbach WK (1975) Quantitative aspects of drinking in alcoholic liver cirrhosis. In: Khanna HM, Israel Y, Kalant H (eds) Alcoholic liver pathology. Adiction research foundation of Ontario, Toronto, pp 1–18Google Scholar
  16. Tuyns AJ, Pequignot G (1984) Greater risk of ascitic cirrhosis in females in relation to alcohol consumption. Int J Epidemiol 13: 53–57PubMedGoogle Scholar
  17. Coates RA, Halliday ML, Rankin JG, Feinman SV, Fisher MM (1986) Risk of fatty infiltration or cirrhosis of the liver in relation to ethanol consumption: a case-control study. Clin Invest Med 9: 26–32PubMedGoogle Scholar
  18. Mann RE, Smart RG, Govoni R (2003) The epidemiology of alcoholic liver disease. Alc Res Health 27: 209–219Google Scholar
  19. Frezza M, Di Padova C, Pozzato G, Terpin M, Baraona E, Lieber CS (1990) High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. N Engl J Med 322: 95–99PubMedCrossRefGoogle Scholar
  20. Kwo PY, Ramchandani VA, O'Connor S, Amann D, Carr LG, Sandrasegaran K, Kopecky KK, Li TK (1998) Gender differences in alcohol metabolism: relationship to liver volume and effect of adjusting for body mass. Gastroenterlogy 115: 1552–1557CrossRefGoogle Scholar
  21. Ammon E, Schafer C, Hofmann U, Klotz U (1996) Disposition and first-pass metabolism of ethanol in humans: is it gastric or hepatic and does it depend on gender? Clin Pharmacol Ther 59: 503–513PubMedCrossRefGoogle Scholar
  22. Marshall AW, Kingstone D, Boss M, Morgan MY (1983) Ethanol elimination in males and females: relationship to menstrual cycle and body composition. Hepatology 3: 701–706PubMedCrossRefGoogle Scholar
  23. Mishra L, Sharma S, Potter JJ, Mezey E (1989) More rapid elimination of alcohol in women as compared to their male siblings. Alcohol Clin Exp Res 13: 752–754PubMedCrossRefGoogle Scholar
  24. Li TK, Beard JD, Orr WE, Kwo PY, Ramchandani VA, Thomasson HR (2000) Variation in ethanol pharmakinetics and perceived gender and ethnic differences in alcohol elimination. Alcohol Clin Exp Res 24: 415–416PubMedCrossRefGoogle Scholar
  25. Schenker S (1997) Medical consequences of alcohol abuse: is gender a factor? Alcohol Clin Exp Res 21: 179–181PubMedCrossRefGoogle Scholar
  26. Norton R, Batey R, Dwyer T, MacMahon S (1987) Alcohol consumption and the risk of alcohol related cirrhosis in women. BMJ 295: 80–82PubMedCrossRefGoogle Scholar
  27. Yin M, Ikejima K, Wheeler MD, Bradford BU, Seabra V, Forman DT, Sato N, Thurman RG (2000) Estrogen is involved in early alcohol-induced liver injury in a rat enteral feeding model. Hepatology 31: 117–123PubMedCrossRefGoogle Scholar
  28. Enomoto N, Yamashina S, Schemmer P, Rivera CA, Bradford BU, Enomoto A, Brenner DA, Thurman DG (1999) Estriol sensitizes rat Kupffer cells via gut-derived endotoxin. Am J Physiol Gastrointest Liver Physiol 277: G671–G677Google Scholar
  29. Colantoni A, Idilman R, De Maria N, La Paglia N, Belmonte J, Wezeman F, Emanuele N, Van Thiel DH, Kovacs EJ, Emanuele MA (2003) Hepatic apoptosis and proliferation in male and female rats fed alcohol: Role of Cytokines Alcoholism. Clin Exp Res 27: 1184–1189CrossRefGoogle Scholar
  30. Järvelainen HA, Lukkari TA, Heinaro S, Sippel H, Lindros KO (2001) The antiestrogen toremifene protects against alcoholic liver injury in female rats. J Hepatol 35: 46–52PubMedCrossRefGoogle Scholar
  31. Chrostek L, Jelski W, Szmitkowski M, Puchalski Z (2003) Gender-related differences in hepatic activity of alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in humans. J Clin Lab Anal 17: 93–96PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Department of Internal Medicine IVMedical University of ViennaViennaAustria

Personalised recommendations