Skip to main content
SpringerLink
Log in

Risk factors for hepatocellular carcinoma in patients with chronic liver disease: a case–control study

  • Original paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

The majority of data on risk factors (RFs) for hepatocellular carcinoma (HCC) comes from studies involving populations without underlying liver disease. It is important to evaluate RFs for HCC in patients with chronic liver disease since HCC rarely occurs in those without underlying liver disease. We conducted a hospital-based case–control study of 259 incident HCC cases and 781 controls by convenience sampling between 02/2001 and 12/2009 from the liver clinic at Stanford University Medical Center. The study population was 41% White, 14% Hispanic, 3% African American, 40% Asian American, and 2% other race/ethnicity. RFs were examined through medical records and an in-person questionnaire. Alcohol and tobacco use was calculated by cumulative grams of alcohol or cumulative pack(s) of cigarette consumed over one’s lifetime. Diabetes mellitus (DM) was defined by random glucose level of ≥200 mg/dL. RFs were evaluated using multivariate logistic regression. Independent predictors of HCC risk, after mutual adjustment and additional control for alcohol use, etiology of liver diseases, and DM, included age >40 (OR = 8.5 [2.6–28.3]), male gender (OR = 3.5 [2.2–5.8]), presence of cirrhosis (OR = 2.8 [1.6–4.9]), Asian ethnicity (OR = 2.8 [1.8–4.6]), AFP > 50 (OR = 4.2 [2.6–6.8]), and cumulative lifetime tobacco use of >11,000 packs (OR = 1.7 [1.0–2.9]). Heavy prolonged cigarette smoking, but not alcohol use, was a significant independent predictor for HCC in patients with underlying liver disease. Besides older age, male gender, presence of cirrhosis, and elevated AFP, Asian ethnicity and heavy cumulative tobacco use are strong independent predictors of HCC.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

RF:

Risk factors

HCC:

Hepatocellular carcinoma

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

DM:

Diabetes mellitus

AFP:

Alpha-fetoprotein

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

MELD:

Model for end-stage liver disease

CTP:

Child-Turcotte-Pugh

References

  1. Parkin DM (2001) Global cancer statistics in the year 2000. Lancet Oncol 2:533–543

    Article  PubMed  CAS  Google Scholar 

  2. Mazzanti R, Gramantieri L, Bolondi L (2008) Hepatocellular carcinoma: epidemiology and clinical aspects. Mol Aspects Med 29:130–143

    Article  PubMed  Google Scholar 

  3. El-Serag HB, Rudolph KL (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132:2557–2576

    Article  PubMed  CAS  Google Scholar 

  4. Nguyen MH, Keeffe EB (2005) General management. Best Pract Res Clin Gastroenterol 19:161–174

    Article  PubMed  Google Scholar 

  5. Kanwal F, El-Serag HB (2009) Hepatocellular cancer care: cost is important but only one factor of disease burden. J Hepatol 50:10–12

    Article  PubMed  Google Scholar 

  6. Donato F, Tagger A, Gelatti U et al (2002) Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol 155:323–331

    Article  PubMed  CAS  Google Scholar 

  7. Di Bisceglie AM, Lyra AC, Schwartz M et al (2003) Hepatitis C-related hepatocellular carcinoma in the United States: influence of ethnic status. Am J Gastroenterol 98:2060–2063

    Article  PubMed  Google Scholar 

  8. Parkin DM (2006) The global health burden of infection-associated cancers in the year 2002. Int J Cancer 118:3030–3044

    Article  PubMed  CAS  Google Scholar 

  9. El-Serag HB (2004) Hepatocellular carcinoma: recent trends in the United States. Gastroenterology 127:S27–S34

    Article  PubMed  Google Scholar 

  10. Gomaa AI, Khan SA, Toledano MB, Waked I, Taylor-Robinson SD (2008) Hepatocellular carcinoma: epidemiology, risk factors and pathogenesis. World J Gastroenterol 14:4300–4308

    Article  PubMed  Google Scholar 

  11. Nguyen MH, Whittemore AS, Garcia RT et al (2004) Role of ethnicity in risk for hepatocellular carcinoma in patients with chronic hepatitis C and cirrhosis. Clin Gastroenterol Hepatol 2:820–824

    Article  PubMed  Google Scholar 

  12. Chin PL, Chu DZ, Clarke KG, Odom-Maryon T, Yen Y, Wagman LD (1999) Ethnic differences in the behavior of hepatocellular carcinoma. Cancer 85:1931–1936

    PubMed  CAS  Google Scholar 

  13. Hassan MM, Hwang LY, Hatten CJ et al (2002) Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus. Hepatology 36:1206–1213

    Article  PubMed  CAS  Google Scholar 

  14. Mukaiya M, Nishi M, Miyake H, Hirata K (1998) Chronic liver diseases for the risk of hepatocellular carcinoma: a case-control study in Japan. Etiologic association of alcohol consumption, cigarette smoking and the development of chronic liver diseases. Hepatogastroenterology 45:2328–2332

    PubMed  CAS  Google Scholar 

  15. Chen ZM, Liu BQ, Boreham J, Wu YP, Chen JS, Peto R (2003) Smoking and liver cancer in China: case-control comparison of 36,000 liver cancer deaths vs. 17,000 cirrhosis deaths. Int J Cancer 107:106–112

    Article  PubMed  CAS  Google Scholar 

  16. Mizoue T, Tokui N, Nishisaka K et al (2000) Prospective study on the relation of cigarette smoking with cancer of the liver and stomach in an endemic region. Int J Epidemiol 29:232–237

    Article  PubMed  CAS  Google Scholar 

  17. Tanaka K, Hirohata T, Takeshita S et al (1992) Hepatitis B virus, cigarette smoking and alcohol consumption in the development of hepatocellular carcinoma: a case-control study in Fukuoka. Jpn Int J Cancer 51:509–514

    Article  CAS  Google Scholar 

  18. La Vecchia C, Negri E, Decarli A, D’Avanzo B, Franceschi S (1988) Risk factors for hepatocellular carcinoma in northern Italy. Int J Cancer 42:872–876

    PubMed  Google Scholar 

  19. Evans AA, Chen G, Ross EA, Shen FM, Lin WY, London WT (2002) Eight-year follow-up of the 90,000-person Haimen City cohort: I. Hepatocellular carcinoma mortality, risk factors, and gender differences. Cancer Epidemiol Biomarkers Prev 11:369–376

    PubMed  Google Scholar 

  20. El-Serag HB, Hampel H, Javadi F (2006) The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. Clin Gastroenterol Hepatol 4:369–380

    Article  PubMed  Google Scholar 

  21. Chang KC, Tsai PS, Hsu MC, Hung SF, Tsai CC, Lu SN (2010) Chronic hepatitis C increased the mortality rates of patients with hepatocellular carcinoma and diabetes mellitus in a triple hepatitis virus endemic community. J Gastroenterol PMID:20054698

  22. Pattullo V, Heathcote J (2009) Hepatitis C and diabetes: one treatment for two diseases? Liver Int PMID:20040049

  23. Patel P, Macerollo A (2010) Diabetes mellitus: diagnosis and screening. Am Fam Physician 81:863–870

    PubMed  Google Scholar 

  24. El-Serag HB (2007) Epidemiology of hepatocellular carcinoma in USA. Hepatol Res 37(Suppl 2):S88–S94

    Article  PubMed  Google Scholar 

  25. Kuper H, Tzonou A, Kaklamani E et al (2000) Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma. Int J Cancer 85:498–502

    Article  PubMed  CAS  Google Scholar 

  26. Zhu K, Moriarty C, Caplan LS, Levine RS (2007) Cigarette smoking and primary liver cancer: a population-based case-control study in US men. Cancer Causes Control 18:315–321

    Article  PubMed  Google Scholar 

  27. Jee SH, Ohrr H, Sull JW, Samet JM (2004) Cigarette smoking, alcohol drinking, hepatitis B, and risk for hepatocellular carcinoma in Korea. J Natl Cancer Inst 96:1851–1856

    Article  PubMed  Google Scholar 

  28. Fujita Y, Shibata A, Ogimoto I et al (2006) The effect of interaction between hepatitis C virus and cigarette smoking on the risk of hepatocellular carcinoma. Br J Cancer 94:737–739

    Article  PubMed  CAS  Google Scholar 

  29. Wang LY, You SL, Lu SN et al (2003) 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 residents in Taiwan. Cancer Causes Control 14:241–250

    Article  PubMed  Google Scholar 

  30. Hassan MM, Spitz MR, Thomas MB et al (2008) 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 123:1883–1891

    Article  PubMed  CAS  Google Scholar 

  31. Wong CR, Garcia RT, Trinh HN et al (2009) Adherence to Screening for Hepatocellular carcinoma among patients with cirrhosis or chronic hepatitis B in a community setting. Dig Dis Sci PMID:19876735

Download references

Conflict of interest

None to disclose.

Author information

Authors and Affiliations

  1. Pacific Health Foundation, San Jose, CA, USA

    Nghi B. Ha & Nghiem B. Ha

  2. University of California San Francisco School of Pharmacy, San Francisco, CA, USA

    Nghi B. Ha

  3. Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA, USA

    Nghiem B. Ha, Aijaz Ahmed, Walid Ayoub, Tami J. Daugherty, Glen A. Lutchman, Gabriel Garcia, Allen D. Cooper, Emmet B. Keeffe & Mindie H. Nguyen

  4. Cancer Prevention Institute of California, Fremont, CA, USA

    Ellen T. Chang

  5. Stanford Cancer Center, Stanford University Medical Center, Stanford, CA, USA

    Ellen T. Chang

  6. Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University Medical Center, 750 Welch Road, Suite 210, Palo Alto, CA, 94304, USA

    Mindie H. Nguyen

Authors
  1. Nghi B. Ha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nghiem B. Ha
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aijaz Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Walid Ayoub
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tami J. Daugherty
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ellen T. Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Glen A. Lutchman
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gabriel Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Allen D. Cooper
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Emmet B. Keeffe
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Mindie H. Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mindie H. Nguyen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ha, N.B., Ha, N.B., Ahmed, A. et al. Risk factors for hepatocellular carcinoma in patients with chronic liver disease: a case–control study. Cancer Causes Control 23, 455–462 (2012). https://doi.org/10.1007/s10552-012-9895-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-012-9895-z

Keywords

Search

Navigation