Hepatocellular carcinoma (HCC) is a highly prevalent and lethal neoplasia. Current data show that it is the main cause of death in patients with cirrhosis. A better knowledge of the natural history of the tumor and the development of staging systems have led to a better prediction of prognosis and to a most appropriate treatment approach. The Barcelona Clinic Liver Cancer (BCLC) system has become the preferred staging system since it takes into account the characteristics of the tumor, the degree of liver impairment and the physical performance. In addition, it is the only one that links prognosis assessment with treatment recommendation. Curative therapies such as resection, transplantation and ablation can improve survival in patients diagnosed at an early HCC stage and may offer a long-term cure. Patients with intermediate-stage HCC benefit from chemoembolization and those diagnosed at an advanced stage benefit from sorafenib, an oral available, multikinase inhibitor with antiangiogenic and antiproliferative effects. Further efforts are needed to improve the survival of this lethal neoplasia.

Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-2917.
Sangiovanni A, Prati GM, Fasani P, Ronchi G, Romeo R, Manini M, Del Ninno E, et al: The natural history of compensated cirrhosis due to hepatitis C virus: a 17-year cohort study of 214 patients. Hepatology 2006;43:1303-1310.
Bruix J, Sherman M: Management of hepatocellular carcinoma: an update. Hepatology 2011;53:1020-1022.
EASL-EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2012;56:908-943.
Ferenci P, Fried M, Labrecque D, Bruix J, Sherman M, Omata M, Heathcote J, et al: Hepatocellular carcinoma (HCC): a global perspective. J Clin Gastroenterol 2010;44:239-245.
Omata M, Lesmana LA, Tateishi R, Chen PJ, Lin SM, Yoshida H, Kudo M, et al: Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int 2010;4:439-474.
Kudo M, Izumi N, Kokudo N, Matsui O, Sakamoto M, Nakashima O, Kojiro M, et al: Management of hepatocellular carcinoma in Japan: consensus-based clinical practice guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version. Dig Dis 2011;29:339-364.
Clavien PA, Lesurtel M, Bossuyt PM, Gores G, Langer B, Perrier A, OLT for HCC Consensus Group: Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol 2012;13:e11-e22.
Verslype C, Rosmorduc O, Rougier P: Hepatocellular carcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012;23:vii41-vii48.
Forner A, Ayuso C, Isabel Real M, Sastre J, Robles R, Sangro B, Varela M, et al: Diagnosis and treatment of hepatocellular carcinoma (in Spanish). Med Clin (Barc) 2009;132:272-287.
International Consensus Group for Hepatocellular Neoplasia: Pathologic diagnosis of early hepatocellular carcinoma: a report of the International Consensus Group for Hepatocellular Neoplasia. Hepatology 2008;49:658-664.
Forner A, Vilana R, Ayuso C, Bianchi L, Solé M, Ayuso JR, Boix L, et al: Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatology 2008;47:97-104.
Sangiovanni A, Manini MA, Iavarone M, Romeo R, Forzenigo LV, Fraquelli M, Massironi S, et al: The diagnostic and economic impact of contrast imaging technique in the diagnosis of small hepatocellular carcinoma in cirrhosis. Gut 2010 59:638-644.
Khalili KT, Kim TK, Jang HJ, Haider MA, Khan L, Guindi M, Sherman M: Optimization of imaging diagnosis of 1-2 cm hepatocellular carcinoma: an analysis of diagnostic performance and resource utilization. J Hepatol 2011;54:723-728.
Vilana R, Forner A, Bianchi L, Garcia-Criado A, Rimola J, de Lope CR, Reig M, et al: Intrahepatic peripheral cholangiocarcinoma in cirrhosis patients may display a vascular pattern similar to hepatocellular carcinoma on contrast-enhanced ultrasound. Hepatology 2010;51:2020-2029.
Chen LD, Xu HX, Xie XY, Xie XH, Xu ZF, Liu GJ, Wang Z, et al: Intrahepatic cholangiocarcinoma and hepatocellular carcinoma: differential diagnosis with contrast-enhanced ultrasound. Eur Radiol 2010;20:743-753.
El-Serag HB, Engels EA, Landgren O, Chiao E, Henderson L, Amaratunge HC, Giordano TP: Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: a population-based study of U.S. veterans. Hepatology 2009;49:116-123.
Forner A, Reig ME, Rodriguez de Lope C, Bruix J: current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis 2010;30:61-74.
Forner A, Llovet JM, Bruix J: Hepatocellular carcinoma. Lancet 2012;379:1245-1255.
Llovet JM, Bustamante J, Castells A, Vilana R, Ayuso Mdel C, Sala M, Bru C, et al: Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology 1999;29:62-67.
Cabibbo G, Enea M, Attanasio M, Bruix J, Craxi A, Camma C: A meta-analysis of survival rates of untreated patients in randomized clinical trials of hepatocellular carcinoma. Hepatology 2010;51:1274-1283.
Llovet JM, Bru C, Bruix J: Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 1999;19:329-338.
Llovet JM, Burroughs A, Bruix J: Hepatocellular carcinoma. Lancet 2003;362:1907-1917.
Beaugrand M, Sala M, Degos F, Sherman M, Bolondi L, Evans T, Trinchet J, et al: Treatment of advanced hepatocellular carcinoma by seocalcitol (a vit D analogue): an international randomized double-blind placebo-controlled study in 747 patients. J Hepatol 2003;42:17A.
Marrero JA, Fontana RJ, Barrat A, Askari F, Conjeevaram HS, Su GL, Lok AS: Prognosis of hepatocellular carcinoma: comparison of 7 staging systems in an American cohort. Hepatology 2005;41:707-716.
Cillo U, Bassanello M, Vitale A, Grigoletto FA, Burra P, Fagiuoli S, D'Amico F, et al: The critical issue of hepatocellular carcinoma prognostic classification: which is the best tool available? J Hepatol 2004;40:124-131.
Llovet J, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, et al: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378-390.
Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, et al: Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009;10:25-34.
Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, Sherman M, et al: Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst 2008;100:698-711.
D'Amico G, Garcia-Tsao G, Pagliaro L: Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol 2006;44:217-231.
Ikai I, Arii S, Kojiro M, Ichida T, Makuuchi M, Matsuyama Y, Nakanuma Y, et al: Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey. Cancer 2004;101:796-802.
Imamura H, Matsuyama Y, Tanaka E, Ohkubo T, Hasegawa K, Miyagawa S, Sugawara Y, et al: Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol 2003;38:200-207.
Takayasu K, Arii S, Ikai I, Omata M, Okita K, Ichida T, Matsuyama Y, et al: Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology 2006;131:461-469.
Livraghi T, Giorgio A, Marin G, Salmi A, de Sio I, Bolondi L, Pompili M, et al: Hepatocellular carcinoma and cirrhosis in 746 patients: long-term results of percutaneous ethanol injection. Radiology 1995;197:101-108.
Zhu AX, Sahani DV, Duda DG, di Tomaso E, Ancukiewicz M, Catalano OA, Sindhwani V, et al: Efficacy, safety, and potential biomarkers of sunitinib monotherapy in advanced hepatocellular carcinoma: a phase II study. J Clin Oncol 2009;27:3027-3035.
N'Kontchou G, Mahamoudi A, Aout M, Ganne-Carrie N, Grando V, Coderc E, Vicaut E, et al: Radiofrequency ablation of hepatocellular carcinoma: long-term results and prognostic factors in 235 Western patients with cirrhosis. Hepatology 2009;50:1475-1483.
A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology 1998;28:751-755.
Hsu CY, Huang YH, Hsia CY, Su CW, Lin HC, Loong CC, Chiou YY, et al: A new prognostic model for hepatocellular carcinoma based on total tumor volume: the Taipei Integrated Scoring System. J Hepatol 2010;53:108-117.
Llovet JM, Peña CEA, Lathia CD, Shan M, Meinhardt G, Bruix J, Group SIS: Plasma biomarkers as predictors of outcome in patients with advanced hepatocellular carcinoma. Clin Cancer Res 2012;18:2290-2300.
Schoenleber SJ, Kurtz DM, Talwalkar JA, Roberts LR, Gores GJ: Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis. Br J Cancer 2009;100:1385-1392.
Hoshida Y, Villanueva A, Kobayashi M, Peix J, Chiang DY, Camargo A, Gupta S, et al: Gene expression in fixed tissues and outcome in hepatocellular carcinoma. N Engl J Med 2008;359:1995-2004.
Llovet JM, Fuster J, Bruix J: Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 1999;30:1434-1440.
Ishizawa T, Hasegawa K, Aoki T, Takahashi M, Inoue Y, Sano K, Imamura H, et al: Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma. Gastroenterology 2008;134:1908-1916.
Llop E, Berzigotti A, Reig M, Erice E, Reverter E, Seijo S, Abraldes JG, et al: Assessment of portal hypertension by transient elastography in patients with compensated cirrhosis and potentially resectable liver tumors. J Hepatol 2012;56:103-108.
Shiina S, Tateishi R, Arano T, Uchino K, Enooku K, Nakagawa H, Asaoka Y, et al: Radiofrequency ablation for hepatocellular carcinoma: 10-year outcome and prognostic factors. Am J Gastroenterol 2012;107:569-577.
Burrel M, Reig M, Forner A, Barrufet M, Lope CR, Tremosini S, Ayuso C, et al: Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using drug eluting beads. Implications for clinical practice and trial design. J Hepatol 2012;56:1330-1335.
Malagari K, Pomoni M, Moschouris H, Bouma E, Koskinas J, Stefaniotou A, Marinis A, et al: Chemoembolization with doxorubicin-eluting beads for unresectable hepatocellular carcinoma: five-year survival analysis. Cardiovasc Intervent Radiol 2012;35:1119-1128.
Sala M, Fuster J, Llovet JM, Navasa M, Sole M, Varela M, Pons F, et al: High pathological risk of recurrence after surgical resection for hepatocellular carcinoma: an indication for salvage liver transplantation. Liver Transpl 2004;10:1294-1300.
Fuks D, Dokmak S, Paradis V, Diouf M, Durand F, Belghiti J: Benefit of initial resection of hepatocellular carcinoma followed by transplantation in case of recurrence: an intention-to-treat analysis. Hepatology 2012;55:132-140.
Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, et al: Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996;334:693-699.
Bismuth H, Majno PE, Adam R: Liver transplantation for hepatocellular carcinoma. Semin Liver Dis 1999;19:311-322.
Jonas S, Bechstein WO, Steinmuller T, Herrmann M, Radke C, Berg T, Settmacher U, et al: Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis. Hepatology 2001;33:1080-1086.
Mazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiavo M, Mariani L, Camerini T, et al: Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol 2009;10:35-43.
Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, Ascher NL, et al: Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 2001;33:1394-1403.
Duffy JP, Vardanian A, Benjamin E, Watson M, Farmer DG, Ghobrial RM, Lipshutz G, et al: Liver transplantation criteria for hepatocellular carcinoma should be expanded: a 22-year experience with 467 patients at UCLA. Ann Surg 2007;246:502-509, discussion 509-511.
Volk ML, Vijan S, Marrero JA: A novel model measuring the harm of transplanting hepatocellular carcinoma exceeding Milan criteria. Am J Transplant 2008;8:839-846.
Lencioni R: Loco-regional treatment of hepatocellular carcinoma. Hepatology 2010;52:762-773.
Germani G, Pleguezuelo M, Gurusamy K, Meyer T, Isgro G, Burroughs AK: Clinical outcomes of radiofrequency ablation, percutaneous alcohol and acetic acid injection for hepatocelullar carcinoma: a meta-analysis. J Hepatol 2010;52:380-388.
Orlando A, Leandro G, Olivo M, Andriulli A, Cottone M: Radiofrequency thermal ablation vs. percutaneous ethanol injection for small hepatocellular carcinoma in cirrhosis: meta-analysis of randomized controlled trials. Am J Gastroenterol 2009;104:514-524.
Cho YK, Kim JK, Kim MY, Rhim H, Han JK: Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies. Hepatology 2009;49:453-459.
Cho YK, Kim JK, Kim WT, Chung JW: Hepatic resection versus radiofrequency ablation for very early stage hepatocellular carcinoma: a Markov model analysis. Hepatology 2010;51:1284-1290.
Rodríguez de Lope C, Tremosini S, Forner A, Reig M, Bruix J: Management of HCC. J Hepatol 2012;56(suppl):S75-S87.
Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, Ayuso C, et al: Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 2002;359:1734-1739.
Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, Fan ST, et al: Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 2002;35:1164-1171.
Salem R, Lewandowski RJ, Kulik L, Wang E, Riaz A, Ryu RK, Sato KT, et al: Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology 2011;140:497-507, e492.
Sangro B, Carpanese L, Cianni R, Golfieri R, Gasparini D, Ezziddin S, Paprottka PM, et al: Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona Clinic Liver Cancer stages: a European evaluation. Hepatology 2011;54:868-878.
Hilgard P, Hamami M, Fouly AE, Scherag A, Müller S, Ertle J, Heusner T, et al: Radioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival. Hepatology 2010;52:1741-1749.
Sangro B, Inarrairaegui M, Bilbao JI: Radioembolization for hepatocellular carcinoma. J Hepatol 2012;56:464-473.
Llovet JM, Bruix J: Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 2003;37:429-442.
Hanahan D, Weinberg A: Hallmarks of cancer: the next generation. Cell 2011;144:646-674.
Villanueva A, Llovet JM: Targeted therapies for hepatocellular carcinoma. Gastroenterology 2011;140:1410-1426.
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.
You do not currently have access to this content.