Advertisement

Synergistic effect of oral corticosteroids use on risk of hepatocellular carcinoma in high risk populations

  • Shih-Wei Lai
    Affiliations
    College of Medicine, China Medical University, Taichung, Taiwan

    Department of Family Medicine, Taiwan
    Search for articles by this author
  • Cheng-Li Lin
    Affiliations
    College of Medicine, China Medical University, Taichung, Taiwan

    Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
    Search for articles by this author
  • Kuan-Fu Liao
    Correspondence
    Corresponding author at: Department of Internal Medicine, Taichung Tzu Chi General Hospital, No.66, Sec. 1, Fongsing Road, Tanzi District, Taichung City 427, Taiwan.
    Affiliations
    College of Medicine, Tzu Chi University, Hualien, Taiwan

    Department of Internal Medicine, Taichung Tzu Chi General Hospital, Taichung, Taiwan
    Search for articles by this author
Published:March 16, 2018DOI:https://doi.org/10.1016/j.ejim.2018.03.006

      Highlights

      • Many risk factors of hepatocellular carcinoma have been well established.
      • Synergistic effect of oral corticosteroids and risk factors on risk of hepatocellular carcinoma.
      • Long-term use of oral corticosteroids is more likely to develop hepatocellular carcinoma.

      Abstract

      Objective

      Little evidence is available on the relationship between oral corticosteroids use and hepatocellular carcinoma. The objective of this study was to investigate whether oral corticosteroids use correlates with the risk of hepatocellular carcinoma in high risk populations in Taiwan.

      Methods

      Using representative claims database established from the Taiwan National Health Insurance Program with a population coverage rate of 99.6%, we identified 102,182 subjects aged 20–84 years with newly diagnosed hepatocellular carcinoma in 2000–2011 as the cases and 102,182 randomly selected subjects aged 20–84 years without hepatocellular carcinoma as the matched controls.

      Results

      In subjects with any one of comorbidities including alcohol-related disease, chronic liver disease, and diabetes mellitus, the adjusted OR of hepatocellular carcinoma was 29.9 (95% CI 28.7, 31.1) for subjects with never use of oral corticosteroids, and the adjusted OR would increase to 33.7 (95% CI 32.3, 35.3) for those with ever use of oral corticosteroids. The adjusted OR of hepatocellular carcinoma was 1.03 for subjects with increasing cumulative duration of oral corticosteroids use for every one year (95% CI 1.01, 1.06), with a duration-dependent effect. The largest OR occurred in subjects with ever use of oral corticosteroids and concurrently comorbid with alcohol-related disease, chronic liver disease, and diabetes mellitus (adjusted OR 122.7, 95% CI 108.5, 138.8).

      Conclusion

      There is a synergistic effect between oral corticosteroids use and the traditional risk factors on the risk of hepatocellular carcinoma. People with risk factors for hepatocellular carcinoma should receive regular ultrasound surveillance, particularly when they currently use oral corticosteroids.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • WJB J.
        • Buttgereit F.
        Adverse events of glucocorticoids during treatment of rheumatoid arthritis: lessons from cohort and registry studies.
        Rheumatology. 2016; 55: ii3-ii5
        • Mapel D.W.
        • Roberts M.H.
        Management of asthma and chronic obstructive pulmonary disease with combination inhaled corticosteroids and long-acting beta-agonists: a review of comparative effectiveness research.
        Drugs. 2014; 74: 737-755
        • Green C.
        • Colquitt J.L.
        • Kirby J.
        • Davidson P.
        • Payne E.
        Clinical and cost-effectiveness of once-daily versus more frequent use of same potency topical corticosteroids for atopic eczema: a systematic review and economic evaluation.
        Health Technol Assess. 2004; 8: 1-120
        • Spies C.M.
        • Strehl C.
        • van der Goes M.C.
        • Bijlsma J.W.
        • Buttgereit F.
        Glucocorticoids.
        Best Pract Res Clin Rheumatol. 2011; 25: 891-900
        • Shalapour S.
        • Karin M.
        Immunity, inflammation, and cancer: an eternal fight between good and evil.
        J Clin Invest. 2015; 125: 3347-3355
        • Trinchieri G.
        Cancer immunity: lessons from infectious diseases.
        J Infect Dis. 2015; 212: S67-73
        • Dietrich K.
        • Schned A.
        • Fortuny J.
        • Heaney J.
        • Marsit C.
        • Kelsey K.T.
        • et al.
        Glucocorticoid therapy and risk of bladder cancer.
        Br J Cancer. 2009; 101: 1316-1320
        • Sorensen G.V.
        • Cronin-Fenton D.P.
        • Sorensen H.T.
        • Ulrichsen S.P.
        • Pedersen L.
        • Lash T.L.
        Use of glucocorticoids and risk of breast cancer: a Danish population-based case-control study.
        Breast Cancer Res. 2012; 14: R21
        • Ostenfeld E.B.
        • Erichsen R.
        • Thorlacius-Ussing O.
        • Riis A.H.
        • Sorensen H.T.
        Use of systemic glucocorticoids and the risk of colorectal cancer.
        Aliment Pharmacol Ther. 2013; 37: 146-152
        • Ministry of Health and Welfare Taiwan
        Statistics of causes of death.
        http://www.mohw.gov.tw/EN/Ministry/Index.aspx
        Date: 2016
        Date accessed: November 1, 2017
        • Lai S.W.
        • Lin C.L.
        • Liao K.F.
        Nation-based case-control study investigating the relationship between oral corticosteroids use and pulmonary tuberculosis.
        Eur J Intern Med. 2017; 43: 53-57
        • Lai S.W.
        • Lin C.L.
        • Liao K.F.
        Use of oral corticosteroids and risk of hip fracture in the elderly in a case-control study.
        Front Pharmacol. 2017; 8: 625
        • Lai S.W.
        • Lin C.L.
        • Liao K.F.
        Glaucoma may be a non-memory manifestation of Alzheimer's disease in older people.
        Int Psychogeriatr. 2017; 29: 1535-1541
        • Hsu F.G.
        • Sheu M.J.
        • Lin C.L.
        • Hsieh Y.W.
        • Lai S.W.
        Use of zolpidem and risk of acute pyelonephritis in women: a population-based case-control study in Taiwan.
        J Clin Pharmacol. 2017; 57: 376-381
        • Hung S.C.
        • Lin C.H.
        • Hung H.C.
        • Lin C.L.
        • Lai S.W.
        Use of selective serotonin reuptake inhibitors and risk of hip fracture in the elderly: a case-control study in Taiwan.
        J Am Med Dir Assoc. 2017; 18: 350-354
        • Lai S.W.
        • Lin C.L.
        • Liao K.F.
        Population-based cohort study investigating the association between weight loss and pyogenic liver abscesses.
        Biomed. 2017; 7: 38-43
        • Yang M.D.
        • Lin K.C.
        • Lu M.C.
        • Jeng L.B.
        • Hsiao C.L.
        • Yueh T.C.
        • et al.
        Contribution of matrix metalloproteinases-1 genotypes to gastric cancer susceptibility in Taiwan.
        BioMed-Taiwan. 2017; 7: 18-24
        • Yang J.S.
        • Lu C.C.
        • Kuo S.C.
        • Hsu Y.M.
        • Tsai S.C.
        • Chen S.Y.
        • et al.
        Autophagy and its link to type II diabetes mellitus.
        BioMed-Taiwan. 2017; 7: 1-12
        • Chang W.S.
        • Liu L.C.
        • Hsiao C.L.
        • Su C.H.
        • Wang H.C.
        • Ji H.X.
        • et al.
        The contributions of the tissue inhibitor of metalloproteinase-1 genotypes to triple negative breast cancer risk.
        BioMed-Taiwan. 2016; 6: 23-28
        • Chang L.C.
        • Yu Y.L.
        Dietary components as epigenetic-regulating agents against cancer.
        BioMed-Taiwan. 2016; 6: 9-16
        • Ministry of Health and Welfare Taiwan
        Taiwan Health and Welfare Report.
        http://www.mohw.gov.tw
        Date: 2016
        Date accessed: November 1, 2017
        • Lai S.W.
        • Chen P.C.
        • Liao K.F.
        • Muo C.H.
        • Lin C.C.
        • Sung F.C.
        Risk of hepatocellular carcinoma in diabetic patients and risk reduction associated with anti-diabetic therapy: a population-based cohort study.
        Am J Gastroenterol. 2012; 107: 46-52
        • Tsai T.Y.
        • Livneh H.
        • Hung T.H.
        • Lin I.H.
        • Lu M.C.
        • Yeh C.C.
        Associations between prescribed Chinese herbal medicine and risk of hepatocellular carcinoma in patients with chronic hepatitis B: a nationwide population-based cohort study.
        BMJ Open. 2017; 7e014571
        • Lai S.W.
        • Lin C.L.
        • Liao K.F.
        • Chen W.C.
        No association between depression and risk of hepatocellular carcinoma in older people in Taiwan.
        ISRN Psychiatry. 2013; 2013901987
        • Lai S.W.
        • Liao K.F.
        • Lai H.C.
        • Muo C.H.
        • Sung F.C.
        • Chen P.C.
        Statin use and risk of hepatocellular carcinoma.
        Eur J Epidemiol. 2013; 28: 485-492
        • Cheng K.C.
        • Liao K.F.
        • Lin C.L.
        • Lai S.W.
        Correlation of proton pump inhibitors with pulmonary tuberculosis: a case-control study in Taiwan.
        Front Pharmacol. 2017; 8: 481
        • Lai S.W.
        • Lin C.L.
        • Liao K.F.
        Use of methimazole and risk of acute pancreatitis: a case-control study in Taiwan.
        Indian J Pharm. 2016; 48: 192-195
        • Liao K.F.
        • Lin C.L.
        • Lai S.W.
        Nationwide case-control study examining the association between tamoxifen use and Alzheimer's disease in aged women with breast cancer in Taiwan.
        Front Pharmacol. 2017; 8: 612
        • Lai S.W.
        • Lin C.L.
        • Liao K.F.
        Tamoxifen use correlates with increased risk of the first episode of ischemic cerebrovascular disease in older women with breast cancer: a case-control study in Taiwan.
        Front Pharmacol. 2017; 8: 742
        • Lai S.W.
        • Lin C.L.
        • Liao K.F.
        Zolpidem administration and risk of hepatocellular carcinoma: a case-control study in Taiwan.
        Front Pharmacol. 2017; 8: 767
        • Kao J.H.
        Hepatitis B virus genotypes and hepatocellular carcinoma in Taiwan.
        Intervirology. 2003; 46: 400-407
        • Lee C.M.
        • Hung C.H.
        • Lu S.N.
        • Wang J.H.
        • Tung H.D.
        • Huang W.S.
        • et al.
        Viral etiology of hepatocellular carcinoma and HCV genotypes in Taiwan.
        Intervirology. 2006; 49: 76-81
        • Chen D.S.
        Hepatocellular carcinoma in Taiwan.
        Hepatol Res. 2007; 37: S101-5
        • Wang L.Y.
        • You S.L.
        • Lu S.N.
        • Ho H.C.
        • Wu M.H.
        • Sun C.A.
        • et al.
        Risk of hepatocellular carcinoma and habits of alcohol drinking, betel quid chewing and cigarette smoking: a cohort of 2416 HBsAg-seropositive and 9421 HBsAg-seronegative male people in Taiwan.
        Cancer Causes Control. 2003; 14: 241-250
        • Loomba R.
        • Yang H.I.
        • Su J.
        • Brenner D.
        • Barrett-Connor E.
        • Iloeje U.
        • et al.
        Synergism between obesity and alcohol in increasing the risk of hepatocellular carcinoma: a prospective cohort study.
        Am J Epidemiol. 2013; 177: 333-342
        • Soresi M.
        • La Spada E.
        • Giannitrapani L.
        • Campagna E.
        • Di Gesaro V.
        • Grana W.
        • et al.
        Hepatocellular carcinoma: comparison of two different periods at the same center.
        Eur J Intern Med. 2010; 21: 127-130
        • Keith B.D.
        Systematic review of the clinical effect of glucocorticoids on nonhematologic malignancy.
        BMC Cancer. 2008; 8: 84
        • Juan J.
        • Feld J.J.
        Hepatitis B virus and hepatitis C virus treatment and management in patients receiving immune-modifying agents.
        Curr Opin Rheumatol. 2014; 26: 395-403
        • Huang Y.T.
        • Jen C.L.
        • Yang H.I.
        • Lee M.H.
        • Su J.
        • Lu S.N.
        • et al.
        Lifetime risk and sex difference of hepatocellular carcinoma among patients with chronic hepatitis B and C.
        J Clin Oncol. 2011; 29: 3643-3650
        • Li C.I.
        • Chen H.J.
        • Lai H.C.
        • Liu C.S.
        • Lin W.Y.
        • Li T.C.
        • et al.
        Hyperglycemia and chronic liver diseases on risk of hepatocellular carcinoma in Chinese patients with type 2 diabetes—National cohort of Taiwan Diabetes Study.
        Int J Cancer. 2015; 136: 2668-2679
        • Wami W.M.
        • Buntinx F.
        • Bartholomeeusen S.
        • Goderis G.
        • Mathieu C.
        • Aerts M.
        Influence of chronic comorbidity and medication on the efficacy of treatment in patients with diabetes in general practice.
        Br J Gen Pract. 2013; 63: e267-73
        • Woods C.P.
        • Hazlehurst J.M.
        • Tomlinson J.W.
        Glucocorticoids and non-alcoholic fatty liver disease.
        J Steroid Biochem Mol Biol. 2015; 154: 94-103
        • Ma C.
        • Zhang Q.
        • Greten T.F.
        Nonalcoholic fatty liver disease promotes hepatocellular carcinoma through direct and indirect effects on hepatocytes.
        FEBS J. 2018; 285: 752-762
        • El-Serag H.B.
        Hepatocellular carcinoma.
        N Engl J Med. 2011; 365: 1118-1127
        • Kudo M.
        Early detection and curative treatment of early-stage hepatocellular carcinoma.
        Clin Gastroenterol Hepatol. 2005; 3: S144-8
        • Omata M.
        • Cheng A.L.
        • Kokudo N.
        • Kudo M.
        • Lee J.M.
        • Jia J.
        • et al.
        Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update.
        Hepatol Int. 2017; 11: 317-370
        • Soresi M.
        • Terranova A.
        • Licata A.
        • Serruto A.
        • Montalto G.
        • Brancatelli G.
        • et al.
        Surveillance program for diagnosis of HCC in liver cirrhosis: role of ultrasound Echo patterns.
        Biomed Res Int. 2017; 20174932759