Skip to main content

Sex and Gender Differences in Gastroenterology and Hepatology

  • Chapter
  • First Online:
Sex and Gender Aspects in Clinical Medicine

Abstract

Sex and gender differences regarding the epidemiology, clinical features, natural history, and response to therapies in hepatology and gastroenterology may be of major relevance for clinical medicine but have not yet been studied in detail so far. The mechanisms of sex or gender differences in these fields and their clinical implications are still unclear.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
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

Institutional subscriptions

References

  1. Reuben A. A sheep in wolf’s clothing. Hepatology. 2003;38:1596-1601.

    Article  PubMed  Google Scholar 

  2. Alvarez F. Autoimmune hepatitis and primary sclerosing cholangitis. Clin Liver Dis. 2006;10:89-107, vi.

    Article  PubMed  Google Scholar 

  3. Sherlock S, Dooley J. Diseases of the Liver and Biliary System. London: Blackwell; 2002.

    Google Scholar 

  4. Nalbandian G, Van de Water J, Gish R, et al. Is there a serological difference between men and women with primary biliary cirrhosis? Am J Gastroenterol. 1999;94:2482-2486.

    Article  PubMed  CAS  Google Scholar 

  5. Myers RP, Shaheen AA, Fong A, et al. Epidemiology and natural history of primary biliary cirrhosis in a Canadian health region: a population-based study. Hepatology. 2009;50:1884-1892.

    Article  PubMed  Google Scholar 

  6. Wiesner RH, Grambsch PM, Dickson ER, et al. Primary sclerosing cholangitis: natural history, prognostic factors and survival analysis. Hepatology. 1989;10:430-436.

    Article  PubMed  CAS  Google Scholar 

  7. Bambha K, Kim WR, Talwalkar J, et al. Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a United States community. Gastroenterology. 2003;125: 1364-1369.

    Article  PubMed  Google Scholar 

  8. Babes VT, Blana D, Duiculescu D, Cepanaru S. Investigations on HBe antigen. Note III. HBe system and sex-dependent clearance of HBsAg subtypes. Virologie. 1981;32:261-268.

    PubMed  CAS  Google Scholar 

  9. Babes VT, Lenkei R, Steiner N, Berca C. Apparently healthy HBsAg carriers: sex-dependent difference in ABO blood group distribution, subtype ratio and antigen titer. Virologie. 1978;29:3-8.

    PubMed  CAS  Google Scholar 

  10. Blumberg BS. Sex differences in response to hepatitis B virus. I. History. Arthritis Rheum. 1979;22:1261-1266.

    Article  PubMed  CAS  Google Scholar 

  11. London WT, Drew JS. Sex differences in response to hepatitis B infection among patients receiving chronic dialysis treatment. Proc Natl Acad Sci USA. 1977;74:2561-2563.

    Article  PubMed  CAS  Google Scholar 

  12. Robinson T, Bullen C, Humphries W, Hornell J, Moyes C. The New Zealand hepatitis B screening programme: screening coverage and prevalence of chronic hepatitis B infection. N Z Med J. 2005;118:U1345.

    PubMed  Google Scholar 

  13. Chu CM, Liaw YF, Sheen IS, Lin DY, Huang MJ. Sex difference in chronic hepatitis B virus infection: an appraisal based on the status of hepatitis B e antigen and antibody. Hepatology. 1983;3:947-950.

    Article  PubMed  CAS  Google Scholar 

  14. Chu CM, Sheen IS, Lin SM, Liaw YF. Sex difference in chronic hepatitis B virus infection: studies of serum HBeAg and alanine aminotransferase levels in 10,431 asymptomatic Chinese HBsAg carriers. Clin Infect Dis. 1993;16:709-713.

    Article  PubMed  CAS  Google Scholar 

  15. Woolf IL, El Sheikh N, Cullens H, et al. Enhanced HBsAb production in pathogenesis of fulminant viral hepatitis type B. Br Med J. 1976;2:669-671.

    Article  PubMed  CAS  Google Scholar 

  16. Wang N, Zheng Y, Yu X, Lin W, Chen Y, Jiang Q. Sex-modified effect of hepatitis B virus infection on mortality from primary liver cancer. Am J Epidemiol. 2009;169:990-995.

    Article  PubMed  Google Scholar 

  17. Hislop TG, Teh C, Low A, et al. Hepatitis B knowledge, testing and vaccination levels in Chinese immigrants to British Columbia, Canada. Can J Public Health. 2007;98: 125-129.

    PubMed  Google Scholar 

  18. Bar-Shany S, Green MS, Slepon R, Shinar E. Ethnic differences in the prevalence of anti-hepatitis C antibodies and hepatitis B surface antigen in Israeli blood donors by age, sex, country of birth and origin. J Viral Hepat. 1995;2:139-144.

    Article  PubMed  CAS  Google Scholar 

  19. Chu CM, Lin SM, Hsieh SY, et al. Etiology of sporadic acute viral hepatitis in Taiwan: the role of hepatitis C virus, hepatitis E virus and GB virus-C/hepatitis G virus in an endemic area of hepatitis A and B. J Med Virol. 1999;58:154-159.

    Article  PubMed  CAS  Google Scholar 

  20. Tang S. Seroepidemiological study on hepatitis C virus infection among blood donors from various regions in China. Zhonghua Liu Xing Bing Xue Za Zhi. 1993;14:271-274.

    PubMed  CAS  Google Scholar 

  21. DuBois DB, Gretch D, dela Rosa C, et al. Quantitation of hepatitis C viral RNA in sera of hemodialysis patients: gender-related differences in viral load. Am J Kidney Dis. 1994;24:795-801.

    PubMed  CAS  Google Scholar 

  22. Kang SY, Goldstein MF, Deren S. Gender differences in health status and care among HIV-infected minority drug users. AIDS Care. 2008;20:1146-1151.

    Article  PubMed  Google Scholar 

  23. Rodriguez-Torres M, Rios-Bedoya CF, Rodriguez-Orengo J, et al. Progression to cirrhosis in Latinos with chronic hepatitis C: differences in Puerto Ricans with and without human immunodeficiency virus coinfection and along gender. J Clin Gastroenterol. 2006;40:358-366.

    Article  PubMed  Google Scholar 

  24. Evans JL, Hahn JA, Page-Shafer K, et al. Gender differences in sexual and injection risk behavior among active young injection drug users in San Francisco (the UFO Study). J Urban Health. 2003;80:137-146.

    Article  PubMed  Google Scholar 

  25. Peters MG, Terrault NA. Alcohol use and hepatitis C. Hepatology. 2002;36:S220-S225.

    Article  PubMed  Google Scholar 

  26. Hassan MM, Spitz MR, Thomas MB, et al. Effect of different types of smoking and synergism with hepatitis C virus on risk of hepatocellular carcinoma in American men and women: case-control study. Int J Cancer. 2008;123:1883-1891.

    Article  PubMed  CAS  Google Scholar 

  27. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557-2576.

    Article  PubMed  CAS  Google Scholar 

  28. Yu MC, Tong MJ, Govindarajan S, Henderson BE. Nonviral risk factors for hepatocellular carcinoma in a low-risk population, the non-Asians of Los Angeles County, California. J Natl Cancer Inst. 1991;83:1820-1826.

    Article  PubMed  CAS  Google Scholar 

  29. Naugler WE, Sakurai T, Kim S, et al. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science. 2007;317:121-124.

    Article  PubMed  CAS  Google Scholar 

  30. Okuda K. Hepatocellular carcinoma. J Hepatol. 2000;32:225-237.

    Article  PubMed  CAS  Google Scholar 

  31. Giannitrapani L, Soresi M, La Spada E, Cervello M, D’Alessandro N, Montalto G. Sex hormones and risk of liver tumor. Ann N Y Acad Sci. 2006;1089:228-236.

    Article  PubMed  CAS  Google Scholar 

  32. Neuberger J, Forman D, Doll R, Williams R. Oral contraceptives and hepatocellular carcinoma. Br Med J (Clin Res Ed). 1986;292:1355-1357.

    Article  CAS  Google Scholar 

  33. Forman D, Vincent TJ, Doll R. Cancer of the liver and the use of oral contraceptives. Br Med J (Clin Res Ed). 1986;292:1357-1361.

    Article  CAS  Google Scholar 

  34. Yu MC, Yuan JM. Environmental factors and risk for hepatocellular carcinoma. Gastroenterology. 2004;127:S72-S78.

    Article  PubMed  CAS  Google Scholar 

  35. Wagtmans MJ, Verspaget HW, Lamers CB, van Hogezand RA. Gender-related differences in the clinical course of Crohn’s disease. Am J Gastroenterol. 2001;96:1541-1546.

    Article  PubMed  CAS  Google Scholar 

  36. Loffler A, Glados M. Data on the epidemiology of Crohn disease in the city of Cologne. Med Klin (Munich). 1993;88:516-519.

    CAS  Google Scholar 

  37. Kildebo S, Nordgaard K, Aronsen O, Breckan R, Burhol PG, Jorde R. The incidence of ulcerative colitis in Northern Norway from 1983 to 1986. The Northern Norwegian Gastroenterology Society. Scand J Gastroenterol. 1990;25: 890-896.

    Article  PubMed  CAS  Google Scholar 

  38. Ashley MJ. Smoking and diseases of the gastrointestinal system: an epidemiological review with special reference to sex differences. Can J Gastroenterol. 1997;11:345-352.

    PubMed  CAS  Google Scholar 

  39. Cosnes J, Nion-Larmurier I, Afchain P, Beaugerie L, Gendre JP. Gender differences in the response of colitis to smoking. Clin Gastroenterol Hepatol. 2004;2:41-48.

    Article  PubMed  Google Scholar 

  40. Brenner H, Hoffmeister M, Arndt V, Haug U. Gender differences in colorectal cancer: implications for age at initiation of screening. Br J Cancer. 2007;96:828-831.

    Article  PubMed  CAS  Google Scholar 

  41. Gao RN, Neutel CI, Wai E. Gender differences in colorectal cancer incidence, mortality, hospitalizations and surgical procedures in Canada. J Public Health (Oxf). 2008;30:194-201.

    Article  Google Scholar 

  42. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics. CA Cancer J Clin. 2010;60:277-300.

    Article  PubMed  Google Scholar 

  43. DeCosse JJ, Ngoi SS, Jacobson JS, Cennerazzo WJ. Gender and colorectal cancer. Eur J Cancer Prev. 1993;2:105-115.

    Article  PubMed  CAS  Google Scholar 

  44. Alley PG, McNee RK. Age and sex differences in right colon cancer. Dis Colon Rectum. 1986;29:227-229.

    Article  PubMed  CAS  Google Scholar 

  45. Vobecky J, Leduc C, Devroede G. Sex differences in the changing anatomic distribution of colorectal carcinoma. Cancer. 1984;54:3065-3069.

    Article  PubMed  CAS  Google Scholar 

  46. dos Santos Silva I, Swerdlow AJ. Sex differences in the risks of hormone-dependent cancers. Am J Epidemiol. 1993;138: 10-28.

    PubMed  CAS  Google Scholar 

  47. Kupfer SS, McCaffrey S, Kim KE. Racial and gender disparities in hereditary colorectal cancer risk assessment: the role of family history. J Cancer Educ. 2006;21:S32-S36.

    Article  PubMed  Google Scholar 

  48. McQueen A, Vernon SW, Meissner HI, Rakowski W. Risk perceptions and worry about cancer: does gender make a difference? J Health Commun. 2008;13:56-79.

    Article  PubMed  Google Scholar 

  49. Boutron-Ruault MC, Senesse P, Faivre J, Chatelain N, Belghiti C, Meance S. Foods as risk factors for colorectal cancer: a case-control study in Burgundy (France). Eur J Cancer Prev. 1999;8:229-235.

    Article  PubMed  CAS  Google Scholar 

  50. Geer EB, Shen W. Gender differences in insulin resistance, body composition, and energy balance. Gend Med. 2009;6(Suppl 1):60-75.

    Article  PubMed  Google Scholar 

  51. Giovannucci E. Modifiable risk factors for colon cancer. Gastroenterol Clin North Am. 2002;31:925-943.

    Article  PubMed  Google Scholar 

  52. Chan AT, Giovannucci EL, Meyerhardt JA, Schernhammer ES, Curhan GC, Fuchs CS. Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer. JAMA. 2005;294:914-923.

    Article  PubMed  CAS  Google Scholar 

  53. Flossmann E, Rothwell PM. Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies. Lancet. 2007;369:1603-1613.

    Article  PubMed  CAS  Google Scholar 

  54. Grodstein F, Newcomb PA, Stampfer MJ. Postmenopausal hormone therapy and the risk of colorectal cancer: a review and meta-analysis. Am J Med. 1999;106:574-582.

    Article  PubMed  CAS  Google Scholar 

  55. Lapierre P, Beland K, Martin C, Alvarez F, Alvarez F. Forkhead box p3+ regulatory T cell underlies male resistance to experimental type 2 autoimmune hepatitis. Hepatology. 2010;51:1789-1798.

    Article  PubMed  CAS  Google Scholar 

  56. Talwalkar JA, Lindor KD. Primary biliary cirrhosis. Lancet. 2003;362:53-61.

    Article  PubMed  CAS  Google Scholar 

  57. Parikh-Patel A, Gold E, Utts J, Gershwin ME. The association between gravidity and primary biliary cirrhosis. Ann Epidemiol. 2002;12:264-272.

    Article  PubMed  Google Scholar 

  58. Tanaka A, Lindor K, Gish R, et al. Fetal microchimerism alone does not contribute to the induction of primary biliary cirrhosis. Hepatology. 1999;30:833-838.

    Article  PubMed  CAS  Google Scholar 

  59. Corpechot C, Barbu V, Chazouilleres O, Poupon R. Fetal microchimerism in primary biliary cirrhosis. J Hepatol. 2000;33:696-700.

    Article  PubMed  CAS  Google Scholar 

  60. Fanning PA, Jonsson JR, Clouston AD, et al. Detection of male DNA in the liver of female patients with primary biliary cirrhosis. J Hepatol. 2000;33:690-695.

    Article  PubMed  CAS  Google Scholar 

  61. Invernizzi P, De Andreis C, Sirchia SM, et al. Blood fetal microchimerism in primary biliary cirrhosis. Clin Exp Immunol. 2000;122:418-422.

    Article  PubMed  CAS  Google Scholar 

  62. Stevens AM, McDonnell WM, Mullarkey ME, Pang JM, Leisenring W, Nelson JL. Liver biopsies from human females contain male hepatocytes in the absence of transplantation. Lab Invest. 2004;84:1603-1609.

    Article  PubMed  Google Scholar 

  63. DeLoia JA, Burk RD, Gearhart JD. Developmental regulation of hepatitis B surface antigen expression in two lines of hepatitis B virus transgenic mice. J Virol. 1989;63:4069-4073.

    PubMed  CAS  Google Scholar 

  64. Alward WL, McMahon BJ, Hall DB, Heyward WL, Francis DP, Bender TR. The long-term serological course of asymptomatic hepatitis B virus carriers and the development of primary hepatocellular carcinoma. J Infect Dis. 1985;151: 604-609.

    Article  PubMed  CAS  Google Scholar 

  65. Zacharakis GH, Koskinas J, Kotsiou S, et al. Natural history of chronic HBV infection: a cohort study with up to 12 years follow-up in North Greece (part of the Interreg I-II/EC-project). J Med Virol. 2005;77:173-179.

    Article  PubMed  CAS  Google Scholar 

  66. Grossman CJ. Interactions between the gonadal steroids and the immune system. Science. 1985;227:257-261.

    Article  PubMed  CAS  Google Scholar 

  67. Lawrence T, Hageman T, Balkwill F. Cancer. Sex, cytokines, and cancer. Science. 2007;317:51-52.

    Article  PubMed  CAS  Google Scholar 

  68. Wang Y, Cui F, Lv Y, et al. HBsAg and HBx knocked into the p21 locus causes hepatocellular carcinoma in mice. Hepatology. 2004;39:318-324.

    Article  PubMed  CAS  Google Scholar 

  69. Rogers AB, Theve EJ, Feng Y, et al. Hepatocellular carcinoma associated with liver-gender disruption in male mice. Cancer Res. 2007;67:11536-11546.

    Article  PubMed  CAS  Google Scholar 

  70. Rossini GP, Baldini GM, Villa E, Manenti F. Characterization of estrogen receptor from human liver. Gastroenterology. 1989;96:1102-1109.

    PubMed  CAS  Google Scholar 

  71. Tamoxifen in treatment of hepatocellular carcinoma: a randomised controlled trial. CLIP Group (Cancer of the Liver Italian Programme). Lancet 1998;352:17-20.

    Google Scholar 

  72. Liu CL, Fan ST, Ng IO, Lo CM, Poon RT, Wong J. Treatment of advanced hepatocellular carcinoma with tamoxifen and the correlation with expression of hormone receptors: a prospective randomized study. Am J Gastroenterol. 2000;95:218-222.

    Article  PubMed  CAS  Google Scholar 

  73. Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020-1022. doi:10.1002/hep. 24199.

    Article  PubMed  Google Scholar 

  74. Yu MW, Chang HC, Chang SC, et al. Role of reproductive factors in hepatocellular carcinoma: impact on hepatitis B- and C-related risk. Hepatology. 2003;38:1393-1400.

    PubMed  Google Scholar 

  75. Yu MW, Yang YC, Yang SY, et al. Hormonal markers and hepatitis B virus-related hepatocellular carcinoma risk: a nested case-control study among men. J Natl Cancer Inst. 2001;93:1644-1651.

    Article  PubMed  CAS  Google Scholar 

  76. Sung YM, Tang NL, Lai PB, Chan PK, Chan FK. Re: Hormonal markers and hepatitis B virus-related ­hepatocellular carcinoma risk: a nested case-control study among men. J Natl Cancer Inst. 2003;95:559-560.

    Article  PubMed  CAS  Google Scholar 

  77. Takemoto N, Iizuka N, Yamada-Okabe H, et al. Sex-based molecular profiling of hepatitis C virus-related hepatocellular carcinoma. Int J Oncol. 2005;26:673-678.

    PubMed  CAS  Google Scholar 

  78. Hammond C, Jeffers L, Carr BI, Simon D. Multiple genetic alterations, 4q28, a new suppressor region, and potential gender differences in human hepatocellular carcinoma. Hepatology. 1999;29:1479-1485.

    Article  PubMed  CAS  Google Scholar 

  79. Gustafsson JA, Eneroth P, Hokfelt T, Mode A, Norstedt G, Skett P. Role of the hypothalamo-pituitary-liver axis in sex differences in susceptibility of the liver to toxic agents. Environ Health Perspect. 1981;38:129-141.

    Article  PubMed  CAS  Google Scholar 

  80. Hernberg S, Kauppinen T, Riala R, Korkala ML, Asikainen U. Increased risk for primary liver cancer among women exposed to solvents. Scand J Work Environ Health. 1988;14:356-365.

    PubMed  CAS  Google Scholar 

  81. D’Amour M, Charbonneau M. Sex-related difference in hepatic glutathione conjugation of hexachlorobenzene in the rat. Toxicol Appl Pharmacol. 1992;112:229-234.

    Article  PubMed  Google Scholar 

  82. Hampe J, Shaw SH, Saiz R, et al. Linkage of inflammatory bowel disease to human chromosome 6p. Am J Hum Genet. 1999;65:1647-1655.

    Article  PubMed  CAS  Google Scholar 

  83. Vermeire S, Satsangi J, Peeters M, et al. Evidence for inflammatory bowel disease of a susceptibility locus on the X chromosome. Gastroenterology. 2001;120:834-840.

    Article  PubMed  CAS  Google Scholar 

  84. Fisher SA, Hampe J, Macpherson AJ, et al. Sex stratification of an inflammatory bowel disease genome search shows male-specific linkage to the HLA region of chromosome 6. Eur J Hum Genet. 2002;10:259-265.

    Article  PubMed  CAS  Google Scholar 

  85. Friedrichs F, Brescianini S, Annese V, et al. Evidence of transmission ratio distortion of DLG5 R30Q variant in general and implication of an association with Crohn disease in men. Hum Genet. 2006;119:305-311.

    Article  PubMed  Google Scholar 

  86. Browning BL, Annese V, Barclay ML, et al. Gender-stratified analysis of DLG5 R30Q in 4707 patients with Crohn disease and 4973 controls from 12 Caucasian cohorts. J Med Genet. 2008;45:36-42.

    Article  PubMed  CAS  Google Scholar 

  87. Biank V, Friedrichs F, Babusukumar U, et al. DLG5 R30Q variant is a female-specific protective factor in pediatric onset Crohn’s disease. Am J Gastroenterol. 2007;102:391-398.

    Article  PubMed  CAS  Google Scholar 

  88. Satsangi J, Welsh KI, Bunce M, et al. Contribution of genes of the major histocompatibility complex to susceptibility and disease phenotype in inflammatory bowel disease. Lancet. 1996;347:1212-1217.

    Article  PubMed  CAS  Google Scholar 

  89. Bouma G, Oudkerk Pool M, Crusius JB, et al. Evidence for genetic heterogeneity in inflammatory bowel disease (IBD); HLA genes in the predisposition to suffer from ulcerative colitis (UC) and Crohn’s disease (CD). Clin Exp Immunol. 1997;109:175-179.

    Article  PubMed  CAS  Google Scholar 

  90. Paganini-Hill A. Estrogen replacement therapy and colorectal cancer risk in elderly women. Dis Colon Rectum. 1999;42:1300-1305.

    Article  PubMed  CAS  Google Scholar 

  91. Calle EE, Miracle-McMahill HL, Thun MJ, Heath CW Jr. Estrogen replacement therapy and risk of fatal colon cancer in a prospective cohort of postmenopausal women. J Natl Cancer Inst. 1995;87:517-523.

    Article  PubMed  CAS  Google Scholar 

  92. Crandall CJ. Estrogen replacement therapy and colon cancer: a clinical review. J Womens Health Gend Based Med. 1999;8:1155-1166.

    Article  PubMed  CAS  Google Scholar 

  93. Foley EF, Jazaeri AA, Shupnik MA, Jazaeri O, Rice LW. Selective loss of estrogen receptor beta in malignant human colon. Cancer Res. 2000;60:245-248.

    PubMed  CAS  Google Scholar 

  94. Campbell-Thompson M, Lynch IJ, Bhardwaj B. Expression of estrogen receptor (ER) subtypes and ERbeta isoforms in colon cancer. Cancer Res. 2001;61:632-640.

    PubMed  CAS  Google Scholar 

  95. Strom A, Hartman J, Foster JS, Kietz S, Wimalasena J, Gustafsson JA. Estrogen receptor beta inhibits 17beta-estradiol-stimulated proliferation of the breast cancer cell line T47D. Proc Natl Acad Sci USA. 2004;101:1566-1571.

    Article  PubMed  CAS  Google Scholar 

  96. Martineti V, Picariello L, Tognarini I, et al. ERbeta is a potent inhibitor of cell proliferation in the HCT8 human colon cancer cell line through regulation of cell cycle components. Endocr Relat Cancer. 2005;12:455-469.

    Article  PubMed  CAS  Google Scholar 

  97. Konstantinopoulos PA, Kominea A, Vandoros G, et al. Oestrogen receptor beta (ERbeta) is abundantly expressed in normal colonic mucosa, but declines in colon adenocarcinoma paralleling the tumour’s dedifferentiation. Eur J Cancer. 2003;39:1251-1258.

    Article  PubMed  CAS  Google Scholar 

  98. Lai JC, Cheng YW, Chiou HL, Wu MF, Chen CY, Lee H. Gender difference in estrogen receptor alpha promoter hypermethylation and its prognostic value in non-small cell lung cancer. Int J Cancer. 2005;117:974-980.

    Article  PubMed  CAS  Google Scholar 

  99. Jacobsen BK, Vollset SE, Kvale G. Do reproductive factors influence colorectal cancer survival? J Clin Epidemiol. 1995;48:1119-1122.

    Article  PubMed  CAS  Google Scholar 

  100. Potter JD, Bostick RM, Grandits GA, et al. Hormone replacement therapy is associated with lower risk of adenomatous polyps of the large bowel: the Minnesota Cancer Prevention Research Unit Case-Control Study. Cancer Epidemiol Biomarkers Prev. 1996;5:779-784.

    PubMed  CAS  Google Scholar 

  101. Chlebowski RT, Wactawski-Wende J, Ritenbaugh C, et al. Estrogen plus progestin and colorectal cancer in postmenopausal women. N Engl J Med. 2004;350:991-1004.

    Article  PubMed  CAS  Google Scholar 

  102. Miyake Y, Iwasaki Y, Sakaguchi K, Shiratori Y. Clinical features of Japanese male patients with type 1 autoimmune hepatitis. Aliment Pharmacol Ther. 2006;24:519-523.

    Article  PubMed  CAS  Google Scholar 

  103. Buchel E, Van Steenbergen W, Nevens F, Fevery J. Improvement of autoimmune hepatitis during pregnancy followed by flare-up after delivery. Am J Gastroenterol. 2002;97:3160-3165.

    Article  PubMed  Google Scholar 

  104. Heneghan MA, Norris SM, O’Grady JG, Harrison PM, McFarlane IG. Management and outcome of pregnancy in autoimmune hepatitis. Gut. 2001;48:97-102.

    Article  PubMed  CAS  Google Scholar 

  105. Kramer A, Sommer D, Hahn EG, Riecken EO. German experimental hepatitis B vaccine–influence of variation of dosage schedule, sex and age differences on immunogenicity in health care workers. Klin Wochenschr. 1986;64:688-694.

    Article  PubMed  CAS  Google Scholar 

  106. Shimizu I, Kohno N, Tamaki K, et al. Female hepatology: favorable role of estrogen in chronic liver disease with hepatitis B virus infection. World J Gastroenterol. 2007;13:4295-4305.

    PubMed  CAS  Google Scholar 

  107. Inoue G, Horiike N, Michitaka K, Onji M. Hepatitis C virus clearance is prominent in women in an endemic area. J Gastroenterol Hepatol. 2000;15:1054-1058.

    Article  PubMed  CAS  Google Scholar 

  108. Bakr I, Rekacewicz C, El Hosseiny M, et al. Higher clearance of hepatitis C virus infection in females compared with males. Gut. 2006;55:1183-1187.

    Article  PubMed  CAS  Google Scholar 

  109. Grebely J, Raffa JD, Lai C, Krajden M, Conway B, Tyndall MW. Factors associated with spontaneous clearance of hepatitis C virus among illicit drug users. Can J Gastroenterol. 2007;21:447-451.

    PubMed  Google Scholar 

  110. Schott E, Witt H, Hinrichsen H, et al. Gender-dependent association of CTLA4 polymorphisms with resolution of hepatitis C virus infection. J Hepatol. 2007;46:372-380.

    Article  PubMed  CAS  Google Scholar 

  111. Barrett S, Goh J, Coughlan B, et al. The natural course of hepatitis C virus infection after 22 years in a unique homogenous cohort: spontaneous viral clearance and chronic HCV infection. Gut. 2001;49:423-430.

    Article  PubMed  CAS  Google Scholar 

  112. Paladino N, Fainboim H, Theiler G, et al. Gender susceptibility to chronic hepatitis C virus infection associated with interleukin 10 promoter polymorphism. J Virol. 2006;80: 9144-9150.

    Article  PubMed  CAS  Google Scholar 

  113. Antiretroviral Therapy Cohort Collaboration. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet. 2008;372:293-299.

    Article  Google Scholar 

  114. Kane SV, Sable K, Hanauer SB. The menstrual cycle and its effect on inflammatory bowel disease and irritable bowel syndrome: a prevalence study. Am J Gastroenterol. 1998;93:1867-1872.

    Article  PubMed  CAS  Google Scholar 

  115. Allison J, Herrinton LJ, Liu L, Yu J, Lowder J. Natural history of severe ulcerative colitis in a community-based health plan. Clin Gastroenterol Hepatol. 2008;6:999-1003.

    Article  PubMed  Google Scholar 

  116. Ferrero S, Ragni N. Inflammatory bowel disease: management issues during pregnancy. Arch Gynecol Obstet. 2004;270:79-85.

    Article  PubMed  CAS  Google Scholar 

  117. Habal FM, Ravindran NC. Management of inflammatory bowel disease in the pregnant patient. World J Gastroenterol. 2008;14:1326-1332.

    Article  PubMed  CAS  Google Scholar 

  118. Cosnes J, Carbonnel F, Carrat F, Beaugerie L, Gendre JP. Oral contraceptive use and the clinical course of Crohn’s disease: a prospective cohort study. Gut. 1999;45:218-222.

    Article  PubMed  CAS  Google Scholar 

  119. Kane SV, Reddy D. Hormonal replacement therapy after menopause is protective of disease activity in women with inflammatory bowel disease. Am J Gastroenterol. 2008;103: 1193-1196.

    Article  PubMed  Google Scholar 

  120. Yu AS, Cheung RC, Keeffe EB. Hepatitis B vaccines. Clin Liver Dis. 2004;8:283-300.

    Article  PubMed  Google Scholar 

  121. Su FH, Chen JD, Cheng SH, Lin CH, Liu YH, Chu FY. Seroprevalence of hepatitis-B infection amongst Taiwanese university students 18 years following the commencement of a national hepatitis-B vaccination program. J Med Virol. 2007;79:138-143.

    Article  PubMed  CAS  Google Scholar 

  122. Garly ML, Jensen H, Martins CL, et al. Hepatitis B vaccination associated with higher female than male mortality in Guinea-bissau: an observational study. Pediatr Infect Dis J. 2004;23:1086-1092.

    PubMed  Google Scholar 

  123. Morrey JD, Korba BE, Sidwell RW. Transgenic mice as a chemotherapeutic model for hepatitis B virus infection. Antivir Ther. 1998;3:59-68.

    PubMed  CAS  Google Scholar 

  124. Sezaki H, Suzuki F, Kawamura Y, et al. Poor response to pegylated interferon and ribavirin in older women infected with hepatitis C virus of genotype 1b in high viral loads. Dig Dis Sci. 2009;54:1317-1324.

    Article  PubMed  CAS  Google Scholar 

  125. Kogure T, Ueno Y, Fukushima K, et al. Pegylated interferon plus ribavirin for genotype Ib chronic hepatitis C in Japan. World J Gastroenterol. 2008;14:7225-4230.

    Article  PubMed  CAS  Google Scholar 

  126. Conjeevaram HS, Fried MW, Jeffers LJ, et al. Peginterferon and ribavirin treatment in African American and Caucasian American patients with hepatitis C genotype 1. Gastroenterology. 2006;131:470-477.

    Article  PubMed  CAS  Google Scholar 

  127. Poynard T, McHutchison J, Davis GL, et al. Impact of interferon alfa-2b and ribavirin on progression of liver fibrosis in patients with chronic hepatitis C. Hepatology. 2000;32:1131-1137.

    Article  PubMed  CAS  Google Scholar 

  128. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.

    Article  PubMed  CAS  Google Scholar 

  129. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.

    Article  PubMed  CAS  Google Scholar 

  130. Hadziyannis SJ, Sette H Jr, Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140:346-355.

    PubMed  CAS  Google Scholar 

  131. Zeuzem S, Diago M, Gane E, et al. Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels. Gastroenterology. 2004;127:1724-1732.

    Article  PubMed  CAS  Google Scholar 

  132. McHutchison JG, Lawitz EJ, Shiffman ML, et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.

    Article  PubMed  CAS  Google Scholar 

  133. Narciso-Schiavon JL, Schiavon Lde L, Carvalho-Filho RJ, et al. Gender influence on treatment of chronic hepatitis C genotype 1. Rev Soc Bras Med Trop. 2010;43:217-223.

    Article  PubMed  Google Scholar 

  134. Northup PG, Pruett TL, Stukenborg GJ, Berg CL. Survival after adult liver transplantation does not correlate with transplant center case volume in the MELD era. Am J Transplant. 2006;6:2455-2462.

    Article  PubMed  CAS  Google Scholar 

  135. Wiesner R, Edwards E, Freeman R, et al. Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology. 2003;124:91-96.

    Article  PubMed  Google Scholar 

  136. Cholongitas E, Shusang V, Marelli L, et al. Review article: renal function assessment in cirrhosis – difficulties and alternative measurements. Aliment Pharmacol Ther. 2007;26:969-978.

    Article  PubMed  CAS  Google Scholar 

  137. Sherman DS, Fish DN, Teitelbaum I. Assessing renal function in cirrhotic patients: problems and pitfalls. Am J Kidney Dis. 2003;41:269-278.

    Article  PubMed  CAS  Google Scholar 

  138. Levey AS, Perrone RD, Madias NE. Serum creatinine and renal function. Annu Rev Med. 1988;39:465-490.

    Article  PubMed  CAS  Google Scholar 

  139. Myers RP, Shaheen AA, Aspinall AI, Quinn RR, Burak KW. Gender, renal function, and outcomes on the liver transplant waiting list: assessment of revised MELD including estimated glomerular filtration rate. J Hepatol. 2011;54(3):462-470.

    Article  PubMed  Google Scholar 

  140. Cholongitas E, Marelli L, Kerry A, et al. Female liver transplant recipients with the same GFR as male recipients have lower MELD scores – a systematic bias. Am J Transplant. 2007;7:685-692.

    Article  PubMed  CAS  Google Scholar 

  141. Huo SC, Huo TI, Lin HC, et al. Is the corrected-creatinine model for end-stage liver disease a feasible strategy to adjust gender difference in organ allocation for liver transplantation? Transplantation. 2007;84:1406-1412.

    Article  PubMed  Google Scholar 

  142. Moylan CA, Brady CW, Johnson JL, Smith AD, Tuttle-Newhall JE, Muir AJ. Disparities in liver transplantation before and after introduction of the MELD score. JAMA. 2008;300:2371-2378.

    Article  PubMed  CAS  Google Scholar 

  143. Axelrod DA, Pomfret EA. Race and sex disparities in liver transplantation: progress toward achieving equal access? JAMA. 2008;300:2425-2426.

    Article  PubMed  CAS  Google Scholar 

  144. Marino IR, Doyle HR, Aldrighetti L, et al. Effect of donor age and sex on the outcome of liver transplantation. Hepatology. 1995;22:1754-1762.

    PubMed  CAS  Google Scholar 

  145. Rustgi VK, Marino G, Halpern MT, Johnson LB, Umana WO, Tolleris C. Role of gender and race mismatch and graft failure in patients undergoing liver transplantation. Liver Transpl. 2002;8:514-518.

    Article  PubMed  Google Scholar 

  146. Zeier M, Dohler B, Opelz G, Ritz E. The effect of donor gender on graft survival. J Am Soc Nephrol. 2002;13:2570-2576.

    Article  PubMed  Google Scholar 

  147. Lehner F, Becker T, Klempnauer J, Borlak J. Gender-incompatible liver transplantation is not a risk factor for patient survival. Liver Int. 2009;29:196-202.

    Article  PubMed  Google Scholar 

  148. Brooks BK, Levy MF, Jennings LW, et al. Influence of donor and recipient gender on the outcome of liver transplantation. Transplantation. 1996;62:1784-1787.

    Article  PubMed  CAS  Google Scholar 

  149. Kane SV, Cohen RD, Aikens JE, Hanauer SB. Prevalence of nonadherence with maintenance mesalamine in quiescent ulcerative colitis. Am J Gastroenterol. 2001;96:2929-2933.

    Article  PubMed  CAS  Google Scholar 

  150. Habal FM, Hui G, Greenberg GR. Oral 5-aminosalicylic acid for inflammatory bowel disease in pregnancy: safety and clinical course. Gastroenterology. 1993;105:1057-1060.

    PubMed  CAS  Google Scholar 

  151. Diav-Citrin O, Park YH, Veerasuntharam G, et al. The safety of mesalamine in human pregnancy: a prospective controlled cohort study. Gastroenterology. 1998;114:23-28.

    Article  PubMed  CAS  Google Scholar 

  152. Toovey S, Hudson E, Hendry WF, Levi AJ. Sulphasalazine and male infertility: reversibility and possible mechanism. Gut. 1981;22:445-451.

    Article  PubMed  CAS  Google Scholar 

  153. Lucey MR, Neuberger JM, Williams R. Primary biliary cirrhosis in men. Gut. 1986;27:1373-1376.

    Article  PubMed  CAS  Google Scholar 

  154. Czaja AJ, Donaldson PT. Gender effects and synergisms with histocompatibility leukocyte antigens in type 1 autoimmune hepatitis. Am J Gastroenterol. 2002;97:2051-2057.

    Article  PubMed  CAS  Google Scholar 

  155. Poynard T, Mathurin P, Lai CL, et al. A comparison of fibrosis progression in chronic liver diseases. J Hepatol. 2003;38:257-265.

    Article  PubMed  CAS  Google Scholar 

  156. Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130:678-686.

    Article  PubMed  Google Scholar 

  157. Zarski JP, Marcellin P, Leroy V, et al. Characteristics of patients with chronic hepatitis B in France: predominant frequency of HBe antigen negative cases. J Hepatol. 2006;45:355-360.

    Article  PubMed  Google Scholar 

  158. Seeff LB. Natural history of chronic hepatitis C. Hepatology. 2002;36:S35-S46.

    Article  PubMed  Google Scholar 

  159. Wright M, Goldin R, Fabre A, et al. Measurement and determinants of the natural history of liver fibrosis in hepatitis C virus infection: a cross sectional and longitudinal study. Gut. 2003;52:574-579.

    Article  PubMed  CAS  Google Scholar 

  160. Bissell DM. Sex and hepatic fibrosis. Hepatology. 1999;29:988-989.

    Article  PubMed  CAS  Google Scholar 

  161. 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;349:825-832.

    Article  PubMed  CAS  Google Scholar 

  162. Tangkijvanich P, Mahachai V, Suwangool P, Poovorawan Y. Gender difference in clinicopathologic features and ­survival of patients with hepatocellular carcinoma. World J Gastroenterol. 2004;10:1547-1550.

    PubMed  Google Scholar 

  163. Ng IO, Ng M, Fan ST. Better survival in women with resected hepatocellular carcinoma is not related to tumor proliferation or expression of hormone receptors. Am J Gastroenterol. 1997;92:1355-1358.

    PubMed  CAS  Google Scholar 

  164. Ng IO, Ng MM, Lai EC, Fan ST. Better survival in female patients with hepatocellular carcinoma. Possible causes from a pathologic approach. Cancer. 1995;75:18-22.

    Article  PubMed  CAS  Google Scholar 

  165. El-Serag HB, Mason AC, Key C. Trends in survival of patients with hepatocellular carcinoma between 1977 and 1996 in the United States. Hepatology. 2001;33:62-65.

    Article  PubMed  CAS  Google Scholar 

  166. Dohmen K, Shigematsu H, Irie K, Ishibashi H. Longer survival in female than male with hepatocellular carcinoma. J Gastroenterol Hepatol. 2003;18:267-272.

    Article  PubMed  Google Scholar 

  167. Bernstein CN, Blanchard JF, Kliewer E, Wajda A. Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer. 2001;91:854-862.

    Article  PubMed  CAS  Google Scholar 

  168. Rutter M, Saunders B, Wilkinson K, et al. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology. 2004;126:451-459.

    Article  PubMed  Google Scholar 

  169. Rakoff-Nahoum S, Medzhitov R. Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88. Science. 2007;317:124-127.

    Article  PubMed  CAS  Google Scholar 

  170. Persson PG, Karlen P, Bernell O, et al. Crohn’s disease and cancer: a population-based cohort study. Gastroenterology. 1994;107:1675-1679.

    PubMed  CAS  Google Scholar 

  171. Ekbom A, Helmick C, Zack M, Adami HO. Increased risk of large-bowel cancer in Crohn’s disease with colonic involvement. Lancet. 1990;336:357-359.

    Article  PubMed  CAS  Google Scholar 

  172. Soderlund S, Granath F, Brostrom O, et al. Inflammatory bowel disease confers a lower risk of colorectal cancer to females than to males. Gastroenterology. 2010;138:1697-1703.

    Article  PubMed  Google Scholar 

Additional References

  1. Bialek SR, Terrault NA. The changing epidemiology and natural history of hepatitis C virus infection. Clin Liver Dis. 2006;10:697-715.

    Article  PubMed  Google Scholar 

  2. Chapman RW. High-dose ursodeoxycholic acid in the treatment of primary sclerosing cholangitis: throwing the urso out with the bathwater? Hepatology. 2009;50:671-673.

    Article  PubMed  CAS  Google Scholar 

  3. Compton CC, Greene FL. The staging of colorectal cancer: 2004 and beyond. CA Cancer J Clin. 2004;54:295-308.

    Article  PubMed  Google Scholar 

  4. Dickson ER, Grambsch PM, Fleming TR, Fisher LD, Langworthy A. Prognosis in primary biliary cirrhosis: model for decision making. Hepatology. 1989;10:1-7.

    Article  PubMed  CAS  Google Scholar 

  5. El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med. 1999;340:745-750.

    Article  PubMed  CAS  Google Scholar 

  6. Harrison LE, Guillem JG, Paty P, Cohen AM. Preoperative carcinoembryonic antigen predicts outcomes in node-negative colon cancer patients: a multivariate analysis of 572 patients. J Am Coll Surg. 1997;185:55-59.

    PubMed  CAS  Google Scholar 

  7. Krawitt EL. Autoimmune hepatitis. N Engl J Med. 1996;334:897-903.

    Article  PubMed  CAS  Google Scholar 

  8. Lee WM. Hepatitis B virus infection. N Engl J Med. 1997;337:1733-1745.

    Article  PubMed  CAS  Google Scholar 

  9. Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ. Primary biliary cirrhosis. Hepatology. 2009;50:291-308.

    Article  PubMed  Google Scholar 

  10. Lok AS. Chronic hepatitis B. N Engl J Med. 2002;346:1682-1683.

    Article  PubMed  Google Scholar 

  11. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2001;34:1225-1241.

    Article  PubMed  CAS  Google Scholar 

  12. Pol S, Lamorthe B, Thi NT, et al. Retrospective analysis of the impact of HIV infection and alcohol use on chronic hepatitis C in a large cohort of drug users. J Hepatol. 1998;28:945-950.

    Article  PubMed  CAS  Google Scholar 

  13. Tong MJ, el-Farra NS, Reikes AR, Co RL. Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med. 1995;332:1463-1466.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Matteo Garcovich .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag London Limited

About this chapter

Cite this chapter

Garcovich, M., Burroughs, A.K. (2012). Sex and Gender Differences in Gastroenterology and Hepatology. In: Oertelt-Prigione, S., Regitz-Zagrosek, V. (eds) Sex and Gender Aspects in Clinical Medicine. Springer, London. https://doi.org/10.1007/978-0-85729-832-4_6

Download citation

  • DOI: https://doi.org/10.1007/978-0-85729-832-4_6

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-0-85729-831-7

  • Online ISBN: 978-0-85729-832-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics