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01-04-2013 | Original Article

Prevalence of Nonalcoholic Steatohepatitis Among Patients with Resectable Intrahepatic Cholangiocarcinoma

Authors: Srinevas K. Reddy, Omar Hyder, J. Wallis Marsh, Georgios C. Sotiropoulos, Andreas Paul, Sorin Alexandrescu, Hugo Marques, Carlo Pulitano, Eduardo Barroso, Luca Aldrighetti, David A. Geller, Christine Sempoux, Vlad Herlea, Irinel Popescu, Robert Anders, Laura Rubbia-Brandt, Jean-Francois Gigot, Giles Mentha, Timothy M. Pawlik

Published in: Journal of Gastrointestinal Surgery | Issue 4/2013

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.

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

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

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.PubMedCrossRef

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.CrossRef

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.PubMedCrossRef

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

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

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

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

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.CrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.CrossRef

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.PubMedCrossRef

25.

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

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.CrossRef

30.

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

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

35.

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

36.

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

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

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.PubMedCrossRef

Title: Prevalence of Nonalcoholic Steatohepatitis Among Patients with Resectable Intrahepatic Cholangiocarcinoma
Authors: Srinevas K. Reddy
Omar Hyder
J. Wallis Marsh
Georgios C. Sotiropoulos
Andreas Paul
Sorin Alexandrescu
Hugo Marques
Carlo Pulitano
Eduardo Barroso
Luca Aldrighetti
David A. Geller
Christine Sempoux
Vlad Herlea
Irinel Popescu
Robert Anders
Laura Rubbia-Brandt
Jean-Francois Gigot
Giles Mentha
Timothy M. Pawlik
Publication date: 01-04-2013
Publisher: Springer US
Published in: Journal of Gastrointestinal Surgery / Issue 4/2013
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-013-2149-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Prevalence of Nonalcoholic Steatohepatitis Among Patients with Resectable Intrahepatic Cholangiocarcinoma

Abstract

Background and Aims

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background and Aims

Methods

Results

Conclusions

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