Gender differences in hepatocellular cancer: disparities in nonalcoholic fatty liver disease/steatohepatitis and liver transplantation

Eric M. Wu , Linda L. Wong , Brenda Y. Hernandez , Jun-Fang Ji , Wei Jia , Sandi A. Kwee , Sumodh Kalathil

Hepatoma Research ›› 2018, Vol. 4 : 66

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Hepatoma Research ›› 2018, Vol. 4:66 DOI: 10.20517/2394-5079.2018.87
Original Article
Original Article

Gender differences in hepatocellular cancer: disparities in nonalcoholic fatty liver disease/steatohepatitis and liver transplantation

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Abstract

Aim: Worldwide, hepatocellular cancer (HCC) is the fourth leading cause of cancer death and occurs 3 times more commonly in males than females. Current surveillance practices do not fully address gender differences in HCC.

Methods: Clinical characteristics and survival were compared between males and females using a prospectively collected database of HCC patients.

Results: In a cohort of 1206 patients, 307 (25%) were female who presented with older age, more non-alcoholic fatty liver disease/steatohepatitis (NAFLD/NASH), family history of HCC, and hypertension. Males (75%) were more likely to use alcohol and cigarettes. Females were more likely to undergo HCC surveillance, have smaller tumor size at diagnosis, and less vascular involvement. Males who met Milan criteria were more likely to undergo liver transplant than women who met the criteria. Median/mean survival was similar between the genders. Multivariate analysis showed that NAFLD/NASH was predictive of mortality for both males and females, age and smoking were predictive of mortality for males, and transplant was predictive of survival for males.

Conclusion: Gender differences in HCC appear related to both behavioral risk factors and biologic factors. Older females with HCC have more NAFLD/NASH and may be overlooked by current surveillance guidelines. These gender disparities may lend support to future studies of gender-based HCC screening.

Keywords

Hepatocellular carcinoma / non-alcoholic fatty liver disease / non-alcoholic steatohepatitis / gender / transplant

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Eric M. Wu, Linda L. Wong, Brenda Y. Hernandez, Jun-Fang Ji, Wei Jia, Sandi A. Kwee, Sumodh Kalathil. Gender differences in hepatocellular cancer: disparities in nonalcoholic fatty liver disease/steatohepatitis and liver transplantation. Hepatoma Research, 2018, 4: 66 DOI:10.20517/2394-5079.2018.87

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References

[1]

Bray F,Soerjomataram I,Torre LA.Glocal cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin2018;

[2]

Ryerson AB,Altekruse SF,Jemal A.Annual report to the nation on the status of cancer, 1975-2012, featuring the increasing incidence of liver cancer.Cancer2016;122:1312-37 PMCID:PMC4840031

[3]

Khan FZ,Wong RJ.Advances in hepatocellular carcinoma: nonalcoholic steatohepatitis-related hepatocellular carcinoma.World J Hepatol2015;7:2155-61 PMCID:PMC4550870

[4]

Kolly P.Surveillance for hepatocellular carcinoma in patients with NASH.Diagnostics (Basel)2016;

[5]

Altekruse SF,Cucinelli JE.Changing hepatocellular carcinoma incidence and liver cancer mortality rates in the United States.Am J Gastroenterol2014;109:542-53 PMCID:PMC4148914

[6]

Bosch FX,Díaz M.Primary liver cancer: worldwide incidence and trends.Gastroenterology2004;127:S5-16

[7]

National Center for Health Statistics (US). Health, United States, 2016: with chartbook on long-term trends in health. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28910066. [Last accessed on 11 Oct 2018]

[8]

Kautzky-Willer A,Pacini G.Sex and gender differences in risk, pathophysiology and complications of type 2 diabetes mellitus.Endocr Rev2016;37:278-316 PMCID:PMC4890267

[9]

Hashimoto E.Prevalence, gender, ethnic variations, and prognosis of NASH.J Gastroenterol2011;46:63-9

[10]

Gan L,Farrell GC.Mechanisms and implications of age-related changes in the liver: nonalcoholic fatty liver disease in the elderly.Curr Gerontol Geriatr Res2011;2011:831536 PMCID:PMC3171768

[11]

Iyer JK,Kaul A,Kaul R.Estrogen receptor expression in chronic hepatitis C and hepatocellular carcinoma pathogenesis.World J Gastroenterol2017;23:6802-16 PMCID:PMC5645614

[12]

Bruix J.Management of hepatocellular carcinoma: an update.Hepatology2011;53:1020-2 PMCID:PMC3084991

[13]

Bruix J,Committee Practice Guidelines.Management of hepatocellular carcinoma.Hepatology2005;42:1208-36

[14]

Edge S,Compton CC,Greene F.AJCC cancer staging manual.7th ed.2009;New YorkSpringer191-9

[15]

Klein SL.Sex influences immune responses to viruses, and efficacy of prophylaxis and treatments for viral diseases.Bioessays2012;34:1050-9 PMCID:PMC4120666

[16]

White DL,Kuzniarek J,Ramsey DJ.Higher serum testosterone is associated with increased risk of advanced hepatitis C-related liver disease in males.Hepatology2012;55:759-68 PMCID:PMC3399504

[17]

Naugler WE,Kim S,Kim K.Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production.Science2007;317:121-4

[18]

Di Martino V,Myers RP,Paradis V.Progression of liver fibrosis in women infected with hepatitis C: long-term benefit of estrogen exposure.Hepatology2004;40:1426-33

[19]

Liu WC.Molecular mechanisms of gender disparity in hepatitis B virus-associated hepatocellular carcinoma.World J Gastroenterol2014;20:6252-61 PMCID:PMC4033463

[20]

Cho LY,Ko KP,Shin A.Coinfection of hepatitis B and C viruses and risk of hepatocellular carcinoma: systematic review and meta-analysis.Int J Cancer2011;128:176-84

[21]

Purohit V,Kwon OS.Roles of alcohol and tobacco exposure in the development of hepatocellular carcinoma.Life Sci2013;92:10 PMCID:PMC3822918

[22]

Makarova-Rusher OV,McNeel TS,Duffy AG.Population attributable fractions of risk factors for hepatocellular carcinoma in the United States.Cancer2016;122:1757-65 PMCID:PMC5548177

[23]

Younossi Z,Marietti M,Henry L.Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention.Nat Rev Gastroenterol Hepatol2018;15:11-20

[24]

Setiawan VW,Lipworth L,Shepherd J.Sex and ethnic differences in the association of obesity with risk of hepatocellular carcinoma.Clin Gastroenterol Hepatol2016;14:309-16 PMCID:PMC4718778

[25]

Yang JD,Pang H,Smith AD.Gender and menopause impact severity of fibrosis among patients with nonalcoholic steatohepatitis.Hepatology2014;59:1406-14 PMCID:PMC3966932

[26]

Ballestri S,Baldelli E,Romagnoli D.NAFLD as a sexual dimorphic disease: role of gender and reproductive status in the development and progression of nonalcoholic fatty liver disease and inherent cardiovascular risk.Adv Ther2017;34:1291-1326 PMCID:PMC5487879

[27]

Singal AG,Tiro J.Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis.PLoS Med2014;11:e1001624 PMCID:PMC3972088

[28]

Singal AG,Rakoski MO,Su GL.Patient involvement in healthcare is associated with higher rates of surveillance for hepatocellular carcinoma.J Clin Gastroenterol2011;45:727-32

[29]

Davila JA,Richardson PA,McGlynn KA.Use of surveillance for hepatocellular carcinoma among patients with cirrhosis in the United States.Hepatology2010;52:132-41 PMCID:PMC3835698

[30]

Palmer LB,Sandler RS.Surveillance for hepatocellular carcinoma in a medicaid cirrhotic population.J Clin Gastroenterol2013;47:713-8 PMCID:PMC3745802

[31]

Ahmed Mohammed HA,Giama NH,Ali HM.Factors influencing surveillance for hepatocellular carcinoma in patients with liver cirrhosis.Liver Cancer2017;6:126-36 PMCID:PMC5340216

[32]

Farinati F,Giacomin A,Del Poggio P.Is female sex a significant favorable prognostic factor in hepatocellular carcinoma?.Eur J Gastroenterol Hepatol2009;21:1212-8

[33]

Simon TG,Chong DQ,Ma Y.Diabetes, metabolic comorbidities, and risk of hepatocellular carcinoma: results from two prospective cohort studies.Hepatology2018;67:1797-1806

[34]

Moylan CA,Johnson JL,Tuttle-Newhall JE.Disparities in liver transplantation before and after introduction of the MELD score.JAMA2008;300:2371-8 PMCID:PMC3640479

[35]

Bryce CL,Arnold RM,Farrell MH.Sociodemographic difference in early access to liver transplant services.Am J Transplant2009;9:2092-101 PMCID:PMC2880404

[36]

Oloruntoba OO.Gender-based disparities in access to and outcomes of liver transplantation.World J Hepatol2015;7:460-7 PMCID:PMC4381169

[37]

Allen AM,Larson JJ,Kim WR.Reduced access to liver transpaltnation in women: role of height, MELD exception scores, and renal function underestimation.Transplantation2018;102:1710-6

[38]

Cholongitas E,Kerry A,Nair D.Female liver transplant recipients with the same GFR as male recipients have lower MELD scores--a systematic bias.Am J Transplant2007;7:685-92

[39]

Lai JC,Vittinghoff E.Height contributes to the gender difference in wait-list mortality under the MELD-based liver allocation system.Am J Transplant2010;10:2658-64 PMCID:PMC3059496

[40]

Yang D,Usher J,Chaudhari P.Impact of sex on the survival of patients with hepatocellular carcinoma: a surveillance, epidemiology, and end results analysis.Cancer2014;120:3707-16

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