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Older Age and Disease Duration Are Highly Associated with Hepatocellular Carcinoma in Patients with Autoimmune Hepatitis

  • Lara Dakhoul
  • Keaton R. Jones
  • Samer Gawrieh
  • Marwan Ghabril
  • Chelsey McShane
  • Raj Vuppalanchi
  • Eduardo Vilar-Gomez
  • Lauren Nephew
  • Naga ChalasaniEmail author
  • Craig LammertEmail author
Original Article

Abstract

Background

Hepatocellular carcinoma (HCC) is rare in patients with autoimmune hepatitis (AIH). However, the overall burden of AIH cirrhosis in causing HCC and patients’ risk factors are not well understood.

Aims

To characterize the proportion of HCC linked to AIH at a large academic health center, and to identify variables associated with HCC in patients with AIH in a case–control study design.

Methods

Over a 14.5-year period, medical records of all patients with HCC were reviewed. Cases are AIH patients identified from the cohort, and controls are patients with AIH without HCC. Three controls were randomly chosen from the Genetic Repository of Autoimmune Liver Disease and Coexisting Exposures database for each eligible case.

Results

Out of 1250 eligible patients, 20 were linked to AIH (1.6%). Their median age was 64 years, 40% men and 100% Caucasian. Ten percent of AIH patients did not have evidence of cirrhosis at HCC diagnosis. The proportion of HCCs due to AIH decreased during the time intervals of the study. Compared to controls, cases were more likely men (40.0% vs. 18%, p = 0.049), with longer AIH duration (median 16 years vs. 5 years, p = 0.004). Prolonged AIH duration (OR 1.68, p = 0.006) and older age (OR 1.15, p = 0.049) were risk factors for HCC.

Conclusions

AIH is a rare cause (1.6%) for HCC in Midwestern USA with a decreasing trend over 14.5 years. Ten percent of AIH-HCC patients did not have cirrhosis at time of HCC diagnosis. Patients with prolonged duration of the disease and older age are at high risk to develop HCC.

Keywords

Liver cancer Autoimmune liver disease Older age Disease duration 

Abbreviations

AIH

Autoimmune hepatitis

HCC

Hepatocellular carcinoma

GRACE

Genetic Repository of Autoimmune Liver Disease and Coexisting Exposures

ANA

Antinuclear antibodies

ASMA

Anti-smooth muscle antibodies

SD

Standard deviation

IQR

Interquartile range

NAFLD

Nonalcoholic fatty liver disease

BMI

Body mass index

MELD

Model for End-Stage Liver Disease

UDCA

Ursodeoxycholic acid

APRI

AST-to-platelet ratio index

AFP

Alpha-fetoprotein

BCLC

Barcelona Clinic Liver Cancer

Notes

Compliance with ethical standards

Conflict of interest

Authors declare no conflicts of interest relevant for this paper.

References

  1. 1.
    van Gerven NM, Verwer BJ, Witte BI, et al. Epidemiology and clinical characteristics of autoimmune hepatitis in the Netherlands. Scand J Gastroenterol. 2014;49:1245–1254.CrossRefGoogle Scholar
  2. 2.
    Heneghan MA, Yeoman AD, Verma S, Smith AD, Longhi MS. Autoimmune hepatitis. Lancet. 2013;382:1433–1444.CrossRefGoogle Scholar
  3. 3.
    Gronbaek L, Vilstrup H, Jepsen P. Autoimmune hepatitis in Denmark: incidence, prevalence, prognosis, and causes of death. A nationwide registry-based cohort study. J Hepatol. 2014;60:612–617.CrossRefGoogle Scholar
  4. 4.
    Tansel A, Katz LH, El-Serag HB, et al. Incidence and determinants of hepatocellular carcinoma in autoimmune hepatitis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2017;15:1207–1217.CrossRefGoogle Scholar
  5. 5.
    Schramm C, Lohse AW. Autoimmune hepatitis on the rise. J Hepatol. 2014;60:478–479.CrossRefGoogle Scholar
  6. 6.
    Montano-Loza AJ, Carpenter HA, Czaja AJ. Predictive factors for hepatocellular carcinoma in type 1 autoimmune hepatitis. Am J Gastroenterol. 2008;103:1944–1951.CrossRefGoogle Scholar
  7. 7.
    Mittal S, El-Serag HB, Sada YH, et al. Hepatocellular carcinoma in the absence of cirrhosis in United States veterans is associated with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2016;14:124–131.e121.CrossRefGoogle Scholar
  8. 8.
    Lammert C, Comerford M, Love J, Bailey JR. Investigation gone viral: application of the social mediasphere in research. Gastroenterology. 2015;149:839–843.CrossRefGoogle Scholar
  9. 9.
    Macaron C, Hanouneh I, Lopez R, Zein NN. S1883 incidence and risk factors of hepatocellular carcinoma in patients with primary biliary cirrhosis and autoimmune hepatitis [Abstract]. Gastroenterology. 2010;138:S-809.CrossRefGoogle Scholar
  10. 10.
    Watanabe T, Soga K, Hirono H, et al. Features of hepatocellular carcinoma in cases with autoimmune hepatitis and primary biliary cirrhosis. World J Gastroenterol. 2009;15:231–239.CrossRefGoogle Scholar
  11. 11.
    Tateishi R, Okanoue T, Fujiwara N, et al. Clinical characteristics, treatment, and prognosis of non-B, non-C hepatocellular carcinoma: a large retrospective multicenter cohort study. J Gastroenterol. 2015;50:350–360.CrossRefGoogle Scholar
  12. 12.
    Park SZ, Nagorney DM, Czaja AJ. Hepatocellular carcinoma in autoimmune hepatitis. Dig Dis Sci. 2000;45:1944–1948.CrossRefGoogle Scholar
  13. 13.
    Teufel A, Weinmann A, Centner C, et al. Hepatocellular carcinoma in patients with autoimmune hepatitis. World J Gastroenterol. 2009;15:578–582.CrossRefGoogle Scholar
  14. 14.
    Lamers MM, van Oijen MG, Pronk M, Drenth JP. Treatment options for autoimmune hepatitis: a systematic review of randomized controlled trials. J Hepatol. 2010;53:191–198.CrossRefGoogle Scholar
  15. 15.
    van Meer S, van Erpecum KJ, Sprengers D, et al. Hepatocellular carcinoma in cirrhotic versus noncirrhotic livers: results from a large cohort in the Netherlands. Eur J Gastroenterol Hepatol. 2016;28:352–359.CrossRefGoogle Scholar
  16. 16.
    Arora A, Sharma P, Tyagi P, et al. Hepatitis B virus infection can cause hepatocellular carcinoma in less advanced liver cirrhosis: a comparative study of 142 patients from North India. J Clin Exp Hepatol. 2013;3:288–295.CrossRefGoogle Scholar
  17. 17.
    Alexander J, Torbenson M, Wu TT, Yeh MM. Non-alcoholic fatty liver disease contributes to hepatocarcinogenesis in non-cirrhotic liver: a clinical and pathological study. J Gastroenterol Hepatol. 2013;28:848–854.CrossRefGoogle Scholar
  18. 18.
    Perumpail RB, Wong RJ, Ahmed A, Harrison SA. Hepatocellular carcinoma in the setting of non-cirrhotic nonalcoholic fatty liver disease and the metabolic syndrome: US experience. Dig Dis Sci. 2015;60:3142–3148.CrossRefGoogle Scholar
  19. 19.
    Danielsson Borssén Å, Lindgren S, Bergquist A, Almer S, Sangfelt P, Werner M. 927 risk for hepatocellular carcinoma in autoimmune hepatitis—is there an indication for surveillance? [Abstract]. J Hepatol. 2013;58:S382–S383.CrossRefGoogle Scholar
  20. 20.
    Wang KK, Czaja AJ. Hepatocellular carcinoma in corticosteroid-treated severe autoimmune chronic active hepatitis. Hepatology. 1988;8:1679–1683.CrossRefGoogle Scholar
  21. 21.
    Wong RJ, Gish R, Frederick T, Bzowej N, Frenette C. Development of hepatocellular carcinoma in autoimmune hepatitis patients: a case series. Dig Dis Sci. 2011;56:578–585.CrossRefGoogle Scholar
  22. 22.
    Floreani A, Niro G, Rosa Rizzotto E, et al. Type I autoimmune hepatitis: clinical course and outcome in an Italian multicentre study. Aliment Pharmacol Ther. 2006;24:1051–1057.CrossRefGoogle Scholar
  23. 23.
    Czaja AJ, Carpenter HA. Distinctive clinical phenotype and treatment outcome of type 1 autoimmune hepatitis in the elderly. Hepatology. 2006;43:532–538.CrossRefGoogle Scholar
  24. 24.
    Yeoman AD, Al-Chalabi T, Karani JB, et al. Evaluation of risk factors in the development of hepatocellular carcinoma in autoimmune hepatitis: implications for follow-up and screening. Hepatology. 2008;48:863–870.CrossRefGoogle Scholar
  25. 25.
    Migita K, Watanabe Y, Jiuchi Y, et al. Hepatocellular carcinoma and survival in patients with autoimmune hepatitis (Japanese National Hospital Organization-autoimmune hepatitis prospective study). Liver Int. 2012;32:837–844.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Lara Dakhoul
    • 1
  • Keaton R. Jones
    • 1
  • Samer Gawrieh
    • 1
  • Marwan Ghabril
    • 1
  • Chelsey McShane
    • 2
  • Raj Vuppalanchi
    • 1
  • Eduardo Vilar-Gomez
    • 1
  • Lauren Nephew
    • 1
  • Naga Chalasani
    • 1
    Email author
  • Craig Lammert
    • 1
    Email author
  1. 1.Division of Gastroenterology and HepatologyIndiana University School of MedicineIndianapolisUSA
  2. 2.Department of Internal MedicineIndiana University School of MedicineIndianapolisUSA

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