Abstract
Introduction: The incidence of hepatocellular cancer (HCC) continues to rise in Europe with a shift of the primary cause towards alcoholic and non-alcoholic fatty liver disease. Metabolic factors like diabetes mellitus and overweight have been identified as significant risk factors for HCC development. Patients and Methods: A retrospective analysis in a large single-center cohort of 650 patients diagnosed with HCC was performed. Demographic characteristics, risk factors, tumor stage at diagnosis and survival were evaluated. Results: Among 650 patients (aged 17-87 years, with a male: female ratio of 4:1), 80.8% had underlying liver cirrhosis. Alcohol abuse was identified as the only risk factor for liver cirrhosis in 52.2% of patients. Viral infection with hepatitis C and hepatitis B was present in 13.7 and 3.6% of patients, respectively. 66.1% of patients with HCC were overweight with a body mass index exceeding 25, 25.5% even exceeding 30; 52% of patients had diabetes mellitus. Conclusion: Strategies aiming at prevention and surveillance of patients at risk to develop HCC in the future need to widen the focus from patients with chronic viral hepatitis and a history of alcohol abuse to patients with metabolic risk factors.
Journal Section:
Original Paper
Keywords:
Hepatocellular cancer,
Epidemiology,
Risk factors,
Obesity ,
Metabolic syndrome,
Staging,
BCLC,
Liver cirrhosis,
Germany
References
1.
El-Serag HB: Hepatocellular carcinoma: an epidemiologic view. J. Clin Gastroenterol 2002;35:S72-S78.
[PubMed]
2.
Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics. CA Cancer J Clin 2002;55:74-108.
3.
Ferenci P, Fried M, Labrecque D, Bruix J, Sherman M, Omata M, et al: World Gastroenterology Organisation Guideline. Hepatocellular carcinoma (HCC): a global perspective. J Gastrointestin Liver Dis 2010;19:311-317.
[PubMed]
4.
Venook A, Papandreou C, Furuse J, de Guevara LL: The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective. Oncologist 2010;15(suppl 4):5-13.
[PubMed]
5.
Schurr R, Stölzel U, Schuppan D, Schwertner C, Steinberg J, Scherübl H: Zunahme des hepatozellulären und des intrahepatischen cholangiozellulären Karzinoms im Nordosten Deutschlands. Dtsch Med Wochenschr 2006;131:1649-1655.
[PubMed]
6.
Whittaker S, Marais R, Zhu AX: The role of signaling pathways in the development and treatment of hepatocellular carcinoma. Oncogene 2010;29:4989-5005.
[PubMed]
7.
Sherman M: Epidemiology of hepatocellular carcinoma. Oncology 2010;78:7-10.
[PubMed]
8.
Bruix J; Sherman M: Management of hepatocellular carcinoma. Hepatology 2005;42:1208-1236.
[PubMed]
9.
Llovet JM, Burroughs A, Bruix J: Hepatocellular carcinoma. Lancet 2003;362:1907-1917.
[PubMed]
10.
Bréchot C: Pathogenesis of hepatitis B virus-related hepatocellular carcinoma: old and new paradigms. Gastroenterology 2004;127:S56-S61.
[PubMed]
11.
Ferenci P, Fried M, Labrecque D, Bruix J, Sherman M, Omata M, et al: Hepatocellular carcinoma (HCC): a global perspective. J Clin Gastroenterol 2010;44:239-245.
[PubMed]
12.
Schütte K, Bornschein J, Malfertheiner P: Hepatocellular carcinoma - epidemiological trends and risk factors. Dig Dis 2009;27:80-92.
[PubMed]
13.
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;54:463-471.
[PubMed]
14.
Mueller S, Millonig G, Seitz H: Alcoholic liver disease and hepatitis C: a frequently underestimated combination. World J Gastroenterol 2009;15:3462-3471.
[PubMed]
15.
Kirchner G, Kirovski G, Hebestreit A, Schölmerich J, Schlitt HJ, Stoeltzing O, et al: Epidemiology and survival of patients with hepatocellular carcinoma in Southern Germany. Int J Clin Exp Med 2010;3:169-179.
[PubMed]
16.
Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, et al: Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001;35:421-430.
[PubMed]
17.
Prospective validation of the CLIP score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma. The Cancer of the Liver Italian Program (CLIP) Investigators. Hepatology 2000;31:840-845.
[PubMed]
18.
Grieco A, Pompili M, Caminiti G, Miele L, Covino M, Alfei B, et al: Prognostic factors for survival in patients with early-intermediate hepatocellular carcinoma undergoing non-surgical therapy: comparison of Okuda, CLIP, and BCLC staging systems in a single Italian centre. Gut 2005;54:411-418.
[PubMed]
19.
Borie F, Bouvier A, Herrero A, Faivre J, Launoy G, Delafosse P, et al: Treatment and prognosis of hepatocellular carcinoma: a population based study in France. J Surg Oncol 2008;98:505-509.
[PubMed]
20.
Chiesa R, Donato F, Tagger A, Favret M, Ribero ML, Nardi G, et al: Etiology of hepatocellular carcinoma in Italian patients with and without cirrhosis. Cancer Epidemiol Biomarkers Prev 2000;9:213-216.
[PubMed]
21.
EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. Eur J Cancer 2012;48:599-641.
[PubMed]
22.
Tiniakos DG: Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis: histological diagnostic criteria and scoring systems. Eur J Gastroenterol Hepatol 2010;22:643-650.
[PubMed]
23.
Llovet JM, Bruix J: Prospective validation of the Cancer of the Liver Italian Program (CLIP) score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma. Hepatology 2000;32:679-680.
[PubMed]
24.
Statistisches Landesamt Sachsen-Anhalt. http://www.statistik.sachsen-anhalt.de/apps/onlinerecherche/pages/recherche/recherche.php Statistisches Landesamt Sachsen-Anhalt.
25.
Kubicka S, Rudolph KL, Hanke M, Tietze MK, Tillmann HL, Trautwein C, et al: Hepatocellular carcinoma in Germany: a retrospective epidemiological study from a low-endemic area. Liver 2000;20:312-318.
[PubMed]
26.
Schoniger-Hekele M, Muller C, Kutilek M, Oesterreicher C, Ferenci P, Gangl A: Hepatocellular carcinoma in Central Europe: prognostic features and survival. Gut 2001;48:103-109.
[PubMed]
27.
Esteban JI, Sauleda S, Quer J: The changing epidemiology of hepatitis C virus infection in Europe. J Hepatol 2008;48:148-162.
[PubMed]
28.
European Association of the Study of the Liver hepatitis C virus clinical practice guidelines. Liver Int 2012;32(suppl 1):2-8.
[PubMed]
29.
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;34:274-285.
[PubMed]
30.
Bellentani S, Marino M: Epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD). Ann Hepatol 2009;8(suppl 1):S4-S8.
[PubMed]
31.
Ruesten A von, Steffen A, Floegel A, van der A DL, Masala G, Tjønneland A, et al: Trend in obesity prevalence in European adult cohort populations during follow-up since 1996 and their predictions to 2015. PLoS ONE 2011;6:e27455.
[PubMed]
32.
Hauner H, Hanisch J, Bramlage P, Steinhagen-Thiessen E, Schunkert H, Jöckel K, et al: Prevalence of undiagnosed type-2-diabetes mellitus and impaired fasting glucose in German primary care: data from the German Metabolic and Cardiovascular Risk Project (GEMCAS). Exp Clin Endocrinol Diabetes 2008;116:18-25.
[PubMed]
33.
Heidemann C, Kroll L, Icks A, Lampert T, Scheidt-Nave C: Prevalence of known diabetes in German adults aged 25-69 years: results from national health surveys over 15 years. Diabet Med 2009;26:655-658.
[PubMed]
34.
International Diabetes Federation. http://www.idf.org/atlasmap/atlasmap.
35.
Neuschwander-Tetri BA, Caldwell SH: Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003;37:1202-1219.
[PubMed]
36.
Hessheimer AJ, Forner A, Varela M, Bruix J: Metabolic risk factors are a major comorbidity in patients with cirrhosis independent of the presence of hepatocellular carcinoma. Eur J Gastroenterol Hepatol 2010;22:1239-1244.
[PubMed]
37.
Milić S, Stimac D: Nonalcoholic fatty liver disease/steatohepatitis: epidemiology, pathogenesis, clinical presentation and treatment. Dig Dis 2012;30:158-162.
[PubMed]
38.
Trichopoulos D, Bamia C, Lagiou P, Fedirko V, Trepo E, Jenab M, et al: Hepatocellular carcinoma risk factors and disease burden in a European cohort: a nested case-control study. J Natl Cancer Inst 2011;103:1686-1695.
[PubMed]
39.
Nair S, Mason A, Eason J, Loss G, Perrillo RP: Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis? Hepatology 2002;36:150-155.
[PubMed]
40.
Caldwell SH, Crespo DM, Kang HS, Al-Osaimi AMS: Obesity and hepatocellular carcinoma. Gastroenterology 2004;127:S97-S103.
[PubMed]
41.
Adami HO, Chow WH, Nyrén O, Berne C, Linet MS, Ekbom A, et al: Excess risk of primary liver cancer in patients with diabetes mellitus. J Natl Cancer Inst 1996;88:1472-477.
[PubMed]
42.
Wideroff L, Gridley G, Mellemkjaer L, Chow WH, Linet M, Keehn S, et al: Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. J Natl Cancer Inst 1997;89:1360-1365.
[PubMed]
43.
Nordenstedt H, White D, El-Serag H: The changing pattern of epidemiology in hepatocellular carcinoma. Dig Liver Dis 2010;42(suppl 3):S206-S214.
[PubMed]
44.
McGlynn K, London W: The global epidemiology of hepatocellular carcinoma: present and future. Clin Liver Dis 2011;15:223-243.
[PubMed]
45.
Patwardhan V, Paul S, Corey KE, Mazhar SM, Richter JM, Thiim M, et al: Hepatocellular carcinoma screening rates vary by etiology of cirrhosis and involvement of gastrointestinal sub-specialists. Dig Dis Sci 2011;56:3316-3322.
[PubMed]
46.
Stroffolini T, Trevisani F, Pinzello G, Brunello F, Tommasini MA, Iavarone M, et al: Changing aetiological factors of hepatocellular carcinoma and their potential impact on the effectiveness of surveillance. Dig Liver Dis 2011;43:875-880.
[PubMed]
47.
Bruix J, Sherman M: Management of hepatocellular carcinoma: an update. Hepatology 2011;53:1020-1022.
[PubMed]
48.
Shao Y, Lin Z, Hsu C, Shen Y, Hsu C, Cheng A: Early alpha-fetoprotein response predicts treatment efficacy of antiangiogenic systemic therapy in patients with advanced hepatocellular carcinoma. Cancer 2010;116:4590-4596.
[PubMed]
49.
Kim BK, Ahn SH, Seong JS, Park JY, Kim DY, Kim JK, et al: Early α-fetoprotein response as a predictor for clinical outcome after localized concurrent chemoradiotherapy for advanced hepatocellular carcinoma. Liver Int 2011;31:369-376.
[PubMed]
50.
Wang W, Xu Y, Yang X, Wang Y, Sun H, Fan J: Prognostic role of diabetes mellitus in hepatocellular carcinoma patients after curative treatments: a meta-analysis. Hepatobiliary Pancreat Dis Int 2011;10:346-355.
[PubMed]
© 2013 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2013
You do not currently have access to this content.
