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Prevalence of Nonalcoholic Steatohepatitis Among Patients with Resectable Intrahepatic Cholangiocarcinoma

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

An Erratum to this article was published on 10 September 2013

Abstract

Background and Aims

The objective of this report was to determine the prevalence of underlying nonalcoholic steatohepatitis in resectable intrahepatic cholangiocarcinoma.

Methods

Demographics, comorbidities, clinicopathologic characteristics, surgical treatments, and outcomes from patients who underwent resection of intrahepatic cholangiocarcinoma at one of eight hepatobiliary centers between 1991 and 2011 were reviewed.

Results

Of 181 patients who underwent resection for intrahepatic cholangiocarcinoma, 31 (17.1 %) had underlying nonalcoholic steatohepatitis. Patients with nonalcoholic steatohepatitis were more likely obese (median body mass index, 30.0 vs. 26.0 kg/m2, p < 0.001) and had higher rates of diabetes mellitus (38.7 vs. 22.0 %, p = 0.05) and the metabolic syndrome (22.6 vs. 10.0 %, p = 0.05) compared with those without nonalcoholic steatohepatitis. Presence and severity of hepatic steatosis, lobular inflammation, and hepatocyte ballooning were more common among nonalcoholic steatohepatitis patients (all p < 0.001). Macrovascular (35.5 vs. 11.3 %, p = 0.01) and any vascular (48.4 vs. 26.7 %, p = 0.02) tumor invasion were more common among patients with nonalcoholic steatohepatitis. There were no differences in recurrence-free (median, 17.0 versus 19.4 months, p = 0.42) or overall (median, 31.5 versus 36.3 months, p = 0.97) survival after surgical resection between patients with and without nonalcoholic steatohepatitis.

Conclusions

Nonalcoholic steatohepatitis affects up to 20 % of patients with resectable intrahepatic cholangiocarcinoma.

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Abbreviations

NASH:

Nonalcoholic steatohepatitis

ICC:

Intrahepatic cholangiocarcinoma

BMI:

Body mass index

AJCC:

American Joint Committee on Cancer

NAFLD:

Nonalcoholic fatty liver disease

HCC:

Hepatocellular carcinoma

NAS:

Nonalcoholic fatty liver disease activity score

References

  1. Hashimoto E, Tokushige K. Prevalence, gender, ethnic variations, and prognosis of NASH. J Gastroenterol 2011;46(Suppl):63–9.

    Article  PubMed  Google Scholar 

  2. Pascale A, Pais R, Ratziu V. An overview of nonalcoholic steatohepatitis: past, present, and future directions. J Gastrointest Liver Dis 2010;19:415–23.

    Google Scholar 

  3. Younossi AM, Stepanova M, Afendy M, Fang Y, Younossi Y, Mir H, et al. Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1998 to 2008. Clin Gastroenterol Hepatol 2011;9:524–30.

    Article  PubMed  Google Scholar 

  4. Michitaka K Nishiguchi S, Aoyagi Y, Hiasa Y, Tokumoto Y, Onji M; Japan Etiology of Liver Cirrhosis Study Group. Etiology of liver cirrhosis in Japan: a nationwide survey. J Gastoenterol 2010;45:86–94.

    Article  Google Scholar 

  5. Bhala N, Angulo P, van der Poorten D, Lee E, Hui JM, Saracco G, et al. The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study. Hepatology 2011;54:1208–16.

    Article  PubMed  Google Scholar 

  6. Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology 2010;51:1820–32.

    Article  PubMed  Google Scholar 

  7. Page JM, Harrison SA. NASH and HCC. Clin Liver Dis 2009;13:631–47.

    Article  PubMed  Google Scholar 

  8. Cohen JC, Horton JD, Hobbs HH. Human fatty liver disease: old questions and new insights. Science 2011;332:1519–23.

    Article  PubMed  CAS  Google Scholar 

  9. Aly EZ, Kleiner DE. Update on fatty liver disease and steatohepatitis. Adv Anat Pathol 2011;18:294–300.

    Article  PubMed  Google Scholar 

  10. Argo CK, Northup PG, Al-Osaimi AMS, Caldwell SH. Systemic review of risk factors for fibrosis progression in non-alcoholic steatohepatitis. J Hepatol 2009;51:371–9.

    Article  PubMed  CAS  Google Scholar 

  11. Reddy SK, Steel JL, Chen HW, DeMateo DJ, Cardinal J, Behari J, et al. Outcomes of curative treatment for hepatocellular caner in nonalcoholic steatohepatitis versus hepatitis C and alcoholic liver disease. Hepatology 2012;55:1809–19.

    Article  PubMed  Google Scholar 

  12. SEER Cancer Statistics Review, 1975–2000. SEER incidence and US mortality rates and trends for the top 15 cancer sites by race/ethnicity. http://seer.cancer.gov/csr/1975_2009_pops09/results_merged/topic_topfifteen.pdf

  13. SEER Cancer Statistics Review, 1975–2000. CSR sections—liver and bile duct. http://seer.cancer.gov/csr/1975_2009_pops2009/results_merged/sect_14_liver_bile.pdf

  14. Hashimoto E, Yatsuji S, Tobari M, Taniai M, Torii N, Tokushige K, Shiratori K. Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. J Gastroenterol 2009;44(Suppl XIX):89–95.

    Article  PubMed  Google Scholar 

  15. Stickel F, Hellerbrand C. Non-alcoholic fatty liver disease as a risk factor for hepatocellular carcinoma: mechanisms and implications. Gut 2010;29:1303–7.

    Article  Google Scholar 

  16. Ascha M, Hanouneh IA, Lopez R, Tamimi TA, Feldstein AF, Zein NN. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology 2010;51:1972–8.

    Article  PubMed  Google Scholar 

  17. Tokushige K, Hasimoto E, Yatsuji S, Tobari M, Taniai M, Torii N, Shiratori K. Prospective study of hepatocellular carcinoma in nonalcoholic steatohepatitis in comparison with hepatocellular carcinoma caused by chronic hepatitis C. J Gastroenterol 2010;45:960–7.

    Article  PubMed  CAS  Google Scholar 

  18. Kawada N, Imanaka K, Kawaguchi T, Tamai C, Ishihara R, Matsunaga T, et al. Hepatocellular carcinoma arising from non-cirrhotic alcoholic steatohepatitis. J Gastroenterol 2009;44:1190–4.

    Article  PubMed  Google Scholar 

  19. Ratziu V, Bonyhay L, Di Martino V, Charlotte F, Cavallaro L, Sayegh-Tainturier MH, et al. Survival, liver failure, and hepatocellular carcinoma in obesity-related cryptogenic cirrhosis. Hepatology 2002;35:1485–93.

    Article  PubMed  Google Scholar 

  20. Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, Carucci P, et al. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 2002; 123:134–40.

    Article  PubMed  Google Scholar 

  21. Yasui K, Hashimoto E, Komorizono Y, Koike K, Arii S, Imai Y, et al. Characteristics of patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma. Clin Gastroenterol Hepatol 2011;9:428–33.

    Article  PubMed  Google Scholar 

  22. Yoshioka Y, Hashimoto E, Yatsuji S, Kaneda H, Taniai M, Tokushige K, Shiratori K. Nonalcoholic steatohepatitis: cirrhosis, hepatocellular carcinoma, and burnt-out NASH. J Gastroenterol 2004;39:1215–8.

    Article  PubMed  Google Scholar 

  23. Welzel TM, Mellemkjaer L, Gloria G, Sakoda LC, Hsing AW, El Ghormli L, et al. Risk factors for intrahepatic cholangiocarcinoma in a low-risk population: A nationwide case–control study. Int J Cancer 2006;120:638–41.

    Article  Google Scholar 

  24. de Jong MC, Nathan H, Sotiropoulos GC, Paul A, Alexandrescu S, Marques H, et al. Intrahepatic cholangiocarcinoma: an international multi-institutional analysis of prognostic factors and lymph node assessment. J Clin Oncol 2011;29:3140–5.

    Article  PubMed  Google Scholar 

  25. Eckel RH, Alberti KGMM, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2010;375:181–3.

    Article  PubMed  Google Scholar 

  26. Alberti KGMM, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009;120:1640–5.

    Article  PubMed  CAS  Google Scholar 

  27. Ascha MS, Hanounch IA, Lopez R, Tamimi TA, Feldstein AF, Zein NN. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology 2010;51:1972–8.

    Article  PubMed  Google Scholar 

  28. Sanyal AJ, Brunt EM, Kleiner DE, Kowdley KV, Chalsani N, Lavine JE, et al. Endpoints and clinical trial design for nonalcoholic steatohepatits. Hepatology 2011;54:344–53.

    Article  PubMed  Google Scholar 

  29. Strasberg SM. Nomenclature of hepatic anatomy and resections: a review of the Brisbane 2000 system. J Hepatobiliary and Pancreat Surg 2005;12:351–5.

    Article  Google Scholar 

  30. Greene FL, Page DL, Fleming ID, Fritz A.. American Joint Committee on Cancer: AJCC Cancer Staging Manual. 6th ed. New York: Springer; 2002.

    Book  Google Scholar 

  31. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41:1313–21.

    Article  PubMed  Google Scholar 

  32. Brunt EM, Kleiner DE, Wilson LA, Belt P, Neuschwander-Tetri BA, NASH Clinical Research Network (CRN). Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology 2011;53:810–20.

    Article  PubMed  CAS  Google Scholar 

  33. Brunt EM, Kleiner DE, Wilson LA, Unalp A, Behling CE, Lavine JE, et al. Portal chronic inflammation in nonalcoholic fatty liver disease (NAFLD): a histologic marker of advanced NAFLD—clinicopathologic correlations from the nonalcoholic steatohepatitis clinical research network. Hepatology 2009;49:809–20.

    Article  PubMed  Google Scholar 

  34. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012;55:2005–23.

    Article  PubMed  Google Scholar 

  35. Kleiner DE, Brunt EM. Nonalcoholic fatty liver disease: pathologic patterns and biopsy evaluation in clinical research. Semin Liver Dis 2012;32:3–13.

    Article  PubMed  CAS  Google Scholar 

  36. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457–81.

    Article  Google Scholar 

  37. Welzel TM, Graubard BI, El-Serag HB, Shaib YH, Hsing AW, Davila JA, McGlynn KA. Risk factors for intra- and extrahepatic cholangiocarcinoma in the United States: a population based case–control study. Clin Gastroenterol Hepatol 2007;5:1221–8.

    Article  PubMed  Google Scholar 

  38. Lefkowitch JH, Morawski JL. Late nonalcoholic fatty liver disease with cirrhosis: a pathologic case of lost or mistaken identity. Semin Liver Dis 2012;32:92–8.

    Article  PubMed  Google Scholar 

  39. Welzel TM, Graubard BI, Zeuzem S, El-Serag HB, Davila JA, McGlynn KA. Metabolic syndrome increases the risk of primary liver cancer in the United States: a study in the SEER-Medicare Database. Hepatology 2011;54:463–71.

    Article  PubMed  Google Scholar 

  40. Reddy SK, Marsh JW, Varley PR, Mock BK, Chopra KB, et al (2012) Underlying steatohepatitis, but not simple hepatic steatosis, increases morbidity after liver resection: a case–control study. Hepatology. doi:10/1002/hep.25935

  41. Paradis V, Zalinski S, Chelbi E, Guedj N, Degos F, Vilgrain V, et al. Hepatocellular carcinoma in patients with metabolic syndrome often develop without significant liver fibrosis: a pathological analysis. Hepatology 2009;49:851–9.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA

    Srinevas K. Reddy

  2. Department of Surgery, Johns Hopkins University School of Medicine, Blalock 688 600 N. Wolfe Street Baltimore, MD, 21287, Baltimore, USA

    Omar Hyder, Robert Anders & Timothy M. Pawlik

  3. Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    J. Wallis Marsh & David A. Geller

  4. Department of Surgery, University Hospital Essen, Essen, Germany

    Georgios C. Sotiropoulos & Andreas Paul

  5. Dan Setlacec Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania

    Sorin Alexandrescu, Vlad Herlea & Irinel Popescu

  6. Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal

    Hugo Marques & Eduardo Barroso

  7. Department of Surgery, Ospedale San Raffaele, Milan, Italy

    Carlo Pulitano & Luca Aldrighetti

  8. Department of Pathology, Cliniques Universitaires Saint-Luc, Brussels, Belgium

    Christine Sempoux

  9. Department of Pathology, Hopitaux Universitaires de Geneve, Geneva, Switzerland

    Laura Rubbia-Brandt, Jean-Francois Gigot & Giles Mentha

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  1. Srinevas K. Reddy
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  2. Omar Hyder
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Correspondence to Timothy M. Pawlik.

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Reddy, S.K., Hyder, O., Marsh, J.W. et al. Prevalence of Nonalcoholic Steatohepatitis Among Patients with Resectable Intrahepatic Cholangiocarcinoma. J Gastrointest Surg 17, 748–755 (2013). https://doi.org/10.1007/s11605-013-2149-x

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  • DOI: https://doi.org/10.1007/s11605-013-2149-x

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