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Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Treatment and survival of non-alcoholic steatohepatitis associated hepatocellular carcinoma

Authors: Arndt Weinmann, Yvonne Alt, Sandra Koch, Carina Nelles, Christoph Düber, Hauke Lang, Gerd Otto, Tim Zimmermann, Jens U Marquardt, Peter R Galle, Marcus A Wörns, Jörn M Schattenberg

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

The incidence of non-alcoholic steatohepatitis (NASH) is increasing worldwide and a poorly defined subset of patients develops end-stage liver disease and hepatocellular carcinoma (HCC). Differences in the biological behaviour, tumour characteristics, associated risk factors, treatment outcomes and overall survival of patients with NASH-HCC remain poorly defined. The aim of this study was to determine and analyze these differences in a large clinical cohort to guide treatment decisions.

Methods

1119 patients with HCC treated in an 11 year period at the University Medical Centre of the Johannes Gutenberg University Mainz were retrospectively analyzed.

Results

Patients with NASH-HCC (n = 45) were older (67.6 vs. 65 years), had an increased frequency of the metabolic syndrome and complications with a higher incidence of obesity (31.1% vs. 14.7%), type II diabetes mellitus (66.7% vs. 37.85%), a higher rate of myocardial infarction (13.3% vs. 4.8%) and apoplectic stroke (8.9% vs. 2.1%) (all p < 0.05). Interestingly, liver function was preserved to a higher extent and MELD scores were significantly lower in NASH-HCC. Nonetheless, resection or orthotopic liver transplantation was performed only in 17.8% and 4.4% of NASH-HCC respectively. Overall survival was lower compared to HCC of other aetiologies. Independent of the underlying aetiology BMI exhibited a positive correlation with overall survival.

Conclusion

Despite retained liver function, patients with NASH-associated HCC showed a decreased overall survival. With regards to the expected increasing prevalence of NASH, it will be necessary to improve screening and surveillance strategies to identify HCC in NASH early and improve survival.
Literature
1.
go back to reference Baffy G, Brunt EM, Caldwell SH. Hepatocellular carcinoma in non-alcoholic fatty liver disease: an emerging menace. J Hepatol. 2012;56(6):1384–91.CrossRefPubMed Baffy G, Brunt EM, Caldwell SH. Hepatocellular carcinoma in non-alcoholic fatty liver disease: an emerging menace. J Hepatol. 2012;56(6):1384–91.CrossRefPubMed
2.
go back to reference El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132(7):2557–76.CrossRefPubMed El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132(7):2557–76.CrossRefPubMed
3.
go back to reference White DL, Kanwal F, El-Serag HB. Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. Clin Gastroenterol Hepatol. 2012;10(12):1342–1359.e1342.CrossRefPubMedPubMedCentral White DL, Kanwal F, El-Serag HB. Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. Clin Gastroenterol Hepatol. 2012;10(12):1342–1359.e1342.CrossRefPubMedPubMedCentral
4.
go back to reference Fabbrini E, Sullivan S, Klein S. Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology. 2010;51(2):679–89.CrossRefPubMedPubMedCentral Fabbrini E, Sullivan S, Klein S. Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology. 2010;51(2):679–89.CrossRefPubMedPubMedCentral
5.
go back to reference Schattenberg JM, Schuppan D. Nonalcoholic steatohepatitis: the therapeutic challenge of a global epidemic. Curr Opin Lipidol. 2011;22(6):479–88.CrossRefPubMed Schattenberg JM, Schuppan D. Nonalcoholic steatohepatitis: the therapeutic challenge of a global epidemic. Curr Opin Lipidol. 2011;22(6):479–88.CrossRefPubMed
6.
go back to reference Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011;34(3):274–85.CrossRefPubMed Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011;34(3):274–85.CrossRefPubMed
7.
go back to reference Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology. 2010;51(5):1820–32.CrossRefPubMed Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology. 2010;51(5):1820–32.CrossRefPubMed
8.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.CrossRefPubMed
9.
go back to reference Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19(3):329–38.CrossRefPubMed Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19(3):329–38.CrossRefPubMed
10.
go back to reference Worns MA, Koch S, Niederle IM, Marquardt JU, Nguyen-Tat M, Gamstatter T, et al. The impact of patient and tumour baseline characteristics on the overall survival of patients with advanced hepatocellular carcinoma treated with sorafenib. Dig Liver Dis. 2013;45(5):408–13.CrossRefPubMed Worns MA, Koch S, Niederle IM, Marquardt JU, Nguyen-Tat M, Gamstatter T, et al. The impact of patient and tumour baseline characteristics on the overall survival of patients with advanced hepatocellular carcinoma treated with sorafenib. Dig Liver Dis. 2013;45(5):408–13.CrossRefPubMed
11.
go back to reference Worns MA, Galle PR. HCC therapies-lessons learned. Nat Rev Gastroenterol Hepatol. 2014;11(7):447–52.CrossRefPubMed Worns MA, Galle PR. HCC therapies-lessons learned. Nat Rev Gastroenterol Hepatol. 2014;11(7):447–52.CrossRefPubMed
12.
13.
go back to reference Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–4.CrossRefPubMed Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–4.CrossRefPubMed
14.
go back to reference Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, 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(16):1640–5.CrossRefPubMed Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, 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(16):1640–5.CrossRefPubMed
15.
go back to reference Ascha MS, 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(6):1972–8.CrossRefPubMed Ascha MS, 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(6):1972–8.CrossRefPubMed
16.
go back to reference Kawada N, Imanaka K, Kawaguchi T, Tamai C, Ishihara R, Matsunaga T, et al. Hepatocellular carcinoma arising from non-cirrhotic nonalcoholic steatohepatitis. J Gastroenterol. 2009;44(12):1190–4.CrossRefPubMed Kawada N, Imanaka K, Kawaguchi T, Tamai C, Ishihara R, Matsunaga T, et al. Hepatocellular carcinoma arising from non-cirrhotic nonalcoholic steatohepatitis. J Gastroenterol. 2009;44(12):1190–4.CrossRefPubMed
17.
go back to reference Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005;129(1):113–21.CrossRefPubMed Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005;129(1):113–21.CrossRefPubMed
18.
go back to reference Yatsuji S, Hashimoto E, Tobari M, Taniai M, Tokushige K, Shiratori K. Clinical features and outcomes of cirrhosis due to non-alcoholic steatohepatitis compared with cirrhosis caused by chronic hepatitis C. J Gastroenterol Hepatol. 2009;24(2):248–54.CrossRefPubMed Yatsuji S, Hashimoto E, Tobari M, Taniai M, Tokushige K, Shiratori K. Clinical features and outcomes of cirrhosis due to non-alcoholic steatohepatitis compared with cirrhosis caused by chronic hepatitis C. J Gastroenterol Hepatol. 2009;24(2):248–54.CrossRefPubMed
19.
go back to reference Schutte K, Kipper M, Kahl S, Bornschein J, Gotze T, Adolf D, et al. Clinical characteristics and time trends in etiology of hepatocellular cancer in Germany. Digestion. 2013;87(3):147–59.CrossRefPubMed Schutte K, Kipper M, Kahl S, Bornschein J, Gotze T, Adolf D, et al. Clinical characteristics and time trends in etiology of hepatocellular cancer in Germany. Digestion. 2013;87(3):147–59.CrossRefPubMed
20.
go back to reference Reddy SK, Steel JL, Chen HW, DeMateo DJ, Cardinal J, Behari J, et al. Outcomes of curative treatment for hepatocellular cancer in nonalcoholic steatohepatitis versus hepatitis C and alcoholic liver disease. Hepatology. 2012;55(6):1809–19.CrossRefPubMed Reddy SK, Steel JL, Chen HW, DeMateo DJ, Cardinal J, Behari J, et al. Outcomes of curative treatment for hepatocellular cancer in nonalcoholic steatohepatitis versus hepatitis C and alcoholic liver disease. Hepatology. 2012;55(6):1809–19.CrossRefPubMed
21.
go back to reference Polesel J, Zucchetto A, Montella M, Dal Maso L, Crispo A, La Vecchia C, et al. The impact of obesity and diabetes mellitus on the risk of hepatocellular carcinoma. Ann Oncol. 2009;20(2):353–7.CrossRefPubMed Polesel J, Zucchetto A, Montella M, Dal Maso L, Crispo A, La Vecchia C, et al. The impact of obesity and diabetes mellitus on the risk of hepatocellular carcinoma. Ann Oncol. 2009;20(2):353–7.CrossRefPubMed
23.
go back to reference Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB. Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut. 2005;54(4):533–9.CrossRefPubMedPubMedCentral Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB. Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut. 2005;54(4):533–9.CrossRefPubMedPubMedCentral
24.
go back to reference Kirchner G, Kirovski G, Hebestreit A, Scholmerich J, Schlitt HJ, Stoeltzing O, et al. Epidemiology and survival of patients with hepatocellular carcinoma in Southern Germany. Int J Clin Exp Med. 2010;3(2):169–79.PubMedPubMedCentral Kirchner G, Kirovski G, Hebestreit A, Scholmerich J, Schlitt HJ, Stoeltzing O, et al. Epidemiology and survival of patients with hepatocellular carcinoma in Southern Germany. Int J Clin Exp Med. 2010;3(2):169–79.PubMedPubMedCentral
25.
go back to reference Ertle J, Dechene A, Sowa JP, Penndorf V, Herzer K, Kaiser G, et al. Non-alcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis. Int J Cancer. 2011;128(10):2436–43.CrossRefPubMed Ertle J, Dechene A, Sowa JP, Penndorf V, Herzer K, Kaiser G, et al. Non-alcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis. Int J Cancer. 2011;128(10):2436–43.CrossRefPubMed
26.
go back to reference Wakai T, Shirai Y, Sakata J, Korita PV, Ajioka Y, Hatakeyama K. Surgical outcomes for hepatocellular carcinoma in nonalcoholic fatty liver disease. J Gastrointest Surg. 2011;15(8):1450–8.CrossRefPubMed Wakai T, Shirai Y, Sakata J, Korita PV, Ajioka Y, Hatakeyama K. Surgical outcomes for hepatocellular carcinoma in nonalcoholic fatty liver disease. J Gastrointest Surg. 2011;15(8):1450–8.CrossRefPubMed
27.
28.
go back to reference Wong RJ, Cheung R, Ahmed A. Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S. Hepatology. 2014;59(6):2188–95. doi:10.1002/hep.26986. Epub 2014 Apr 25.CrossRefPubMed Wong RJ, Cheung R, Ahmed A. Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S. Hepatology. 2014;59(6):2188–95. doi:10.1002/hep.26986. Epub 2014 Apr 25.CrossRefPubMed
29.
go back to reference Dyson J, Jaques B, Chattopadyhay D, Lochan R, Graham J, Das D, et al. Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team. J Hepatol. 2014;60(1):110–7.CrossRefPubMed Dyson J, Jaques B, Chattopadyhay D, Lochan R, Graham J, Das D, et al. Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team. J Hepatol. 2014;60(1):110–7.CrossRefPubMed
30.
go back to reference Siegel AB, Lim EA, Wang S, Brubaker W, Rodriguez RD, Goyal A, et al. Diabetes, body mass index, and outcomes in hepatocellular carcinoma patients undergoing liver transplantation. Transplantation. 2012;94(5):539–43.CrossRefPubMedPubMedCentral Siegel AB, Lim EA, Wang S, Brubaker W, Rodriguez RD, Goyal A, et al. Diabetes, body mass index, and outcomes in hepatocellular carcinoma patients undergoing liver transplantation. Transplantation. 2012;94(5):539–43.CrossRefPubMedPubMedCentral
31.
go back to reference Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625–38.CrossRefPubMed Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625–38.CrossRefPubMed
32.
go back to reference Ong JP, Younossi ZM. Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis. 2007;11(1):1–16. vii.CrossRefPubMed Ong JP, Younossi ZM. Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis. 2007;11(1):1–16. vii.CrossRefPubMed
Metadata
Title
Treatment and survival of non-alcoholic steatohepatitis associated hepatocellular carcinoma
Authors
Arndt Weinmann
Yvonne Alt
Sandra Koch
Carina Nelles
Christoph Düber
Hauke Lang
Gerd Otto
Tim Zimmermann
Jens U Marquardt
Peter R Galle
Marcus A Wörns
Jörn M Schattenberg
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1197-x

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