Skip to main content

Advertisement

SpringerLink
Log in

Management of hepatocellular carcinoma

  • Review – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Hepatocellular carcinoma (HCC), a common cause for cancer-related death, is increasing worldwide. Over the past decade, survival and quality of life of HCC patients have significantly improved due to better prevention strategies, early diagnosis, and improved treatment options. We performed this narrative review to synthesize current status on the HCC management.

Methods

Literature search for publications especially over the last decade, which has changed the paradigm on the management of HCC.

Results

Hepatitis B vaccination and treatment of chronic hepatitis B and C are important measures for HCC prevention. Screening and surveillance for HCC using ultrasonogram and alpha-fetoprotein estimation are directed toward cirrhotics and hepatitis B patients at high risk of HCC. If detected at an early stage, curative treatments for HCC can be used such as tumor resection, ablation and liver transplantation. HCC patients without curative options are managed by loco-regional therapies and systemic chemotherapy. Loco-regional treatments include trans-arterial chemoembolization, radioembolization and combinations of loco-regional plus systemic therapies. Currently, sorafenib is the only FDA-approved systemic therapy and newer better chemotherapeutic agents are being investigated. Palliative care for terminally ill patients with metastatic disease and/or poor functional status focusses on comfort care and symptom control.

Conclusions

In spite of significant advancement in HCC management, its incidence continues to rise. There remains an urgent need to continue refining understanding of HCC and develop strategies to increase utilization of the available preventive measures and curative treatment modalities for HCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Adachi E, Maeda T, Matsumata T, Shirabe K, Kinukawa N, Sugimachi K et al (1995) Risk factors for intrahepatic recurrence in human small hepatocellular carcinoma. Gastroenterology 108(3):768–775

    Article  CAS  PubMed  Google Scholar 

  • Adachi Y, Tsuchihashi J, Shiraishi N, Yasuda K, Etoh T, Kitano S (2003) AFP-producing gastric carcinoma: multivariate analysis of prognostic factors in 270 patients. Oncology 65(2):95–101

    Article  CAS  PubMed  Google Scholar 

  • Bolondi L, Sofia S, Siringo S, Gaiani S, Casali A, Zironi G et al (2001) Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis. Gut 48(2):251–259

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bruix J, Llovet JM (2002) Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology 35(3):519–524

    Article  PubMed  Google Scholar 

  • Bruix J, Castells A, Bosch J, Feu F, Fuster J, Garcia-Pagan JC et al (1996) Surgical resection of hepatocellular carcinoma in cirrhotic patients: prognostic value of preoperative portal pressure. Gastroenterology 111(4):1018–1022

    Article  CAS  PubMed  Google Scholar 

  • Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK et al (2001) Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 35(3):421–430

    Article  CAS  PubMed  Google Scholar 

  • Bruix J, Sala M, Llovet JM (2004) Chemoembolization for hepatocellular carcinoma. Gastroenterology 127(5 Suppl 1):S179–S188

    Article  CAS  PubMed  Google Scholar 

  • Bruix J, Sherman M, American Association for the Study of Liver Diseases (2011) Management of hepatocellular carcinoma: an update. Hepatology 53(3):1020–1022

    Article  PubMed Central  PubMed  Google Scholar 

  • Bruix J, Tak WY, Gasbarrini A, Santoro A, Colombo M, Lim HY, Mazzaferro V, Wiest R, Reig M, Wagner A, Bolondi L (2013) Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: multicentre, open-label, phase II safety study. Eur J Cancer 49(16):3412–3419

    Article  CAS  PubMed  Google Scholar 

  • Castells A, Bruix J, Ayuso C, Bru C, Montanya X, Boix L et al (1995) Transarterial embolization for hepatocellular carcinoma. Antibiotic prophylaxis and clinical meaning of postembolization fever. J Hepatol 22(4):410–415

    Article  CAS  PubMed  Google Scholar 

  • Cescon M, Cucchetti A, Grazi GL, Ferrero A, Vigano L, Ercolani G et al (2009) Indication of the extent of hepatectomy for hepatocellular carcinoma on cirrhosis by a simple algorithm based on preoperative variables. Arch Surg 144(1):57–63; discussion 63

  • Chen DS, Hsu NH, Sung JL, Hsu TC, Hsu ST, Kuo YT et al (1987) A mass vaccination program in Taiwan against hepatitis B virus infection in infants of hepatitis B surface antigen—carrier mothers. JAMA 257(19):2597–2603

    Article  CAS  PubMed  Google Scholar 

  • Chen MS, Li JQ, Zheng Y, Guo RP, Liang HH, Zhang YQ et al (2006) A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg 243(3):321–328

    Article  PubMed Central  PubMed  Google Scholar 

  • Cho YK, Kim JK, Kim MY, Rhim H, Han JK (2009) Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies. Hepatology 49(2):453–459

    Article  PubMed  Google Scholar 

  • Cholongitas E, Mamou C, Rodriguez-Castro KI, Burra P (2014) Mammalian target of rapamycin inhibitors are associated with lower rates of hepatocellular carcinoma recurrence after liver transplantation: a systematic review. Transpl Int. doi:10.1111/tri.12372

  • Chow PK, Tai BC, Tan CK, Machin D, Win KM, Johnson PJ et al (2002) High-dose tamoxifen in the treatment of inoperable hepatocellular carcinoma: a multicenter randomized controlled trial. Hepatology 36(5):1221–1226

    Article  CAS  PubMed  Google Scholar 

  • Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A et al (2012) Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol 13(1):e11–e22

    Article  PubMed Central  PubMed  Google Scholar 

  • Colli A, Fraquelli M, Casazza G, Massironi S, Colucci A, Conte D et al (2006) Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review. Am J Gastroenterol 101(3):513–523

    Article  CAS  PubMed  Google Scholar 

  • Cucchetti A, Cescon M, Bertuzzo V, Bigonzi E, Ercolani G, Morelli MC et al (2011) Can the dropout risk of candidates with hepatocellular carcinoma predict survival after liver transplantation? Am J Transplant 11(8):1696–1704

    Article  CAS  PubMed  Google Scholar 

  • Cucchetti A, Piscaglia F, Cescon M, Ercolani G, Terzi E, Bolondi L et al (2012) Conditional survival after hepatic resection for hepatocellular carcinoma in cirrhotic patients. Clin Cancer Res 18(16):4397–4405

    Article  PubMed  Google Scholar 

  • Davila JA, Henderson L, Kramer JR, Kanwal F, Richardson PA, Duan Z et al (2011) Utilization of surveillance for hepatocellular carcinoma among hepatitis C virus-infected veterans in the United States. Ann Intern Med 154(2):85–93

    Article  PubMed  Google Scholar 

  • Delis SG, Bakoyiannis A, Biliatis I, Athanassiou K, Tassopoulos N, Dervenis C (2009) Model for end-stage liver disease (MELD) score, as a prognostic factor for post-operative morbidity and mortality in cirrhotic patients, undergoing hepatectomy for hepatocellular carcinoma. HPB (Oxford) 11(4):351–357

    Article  Google Scholar 

  • Diouf M, Filleron T, Barbare JC, Fin L, Picard C, Bouché O, Dahan L, Paoletti X, Bonnetain F (2013) The added value of quality of life (QoL) for prognosis of overall survival in patients with palliative hepatocellular carcinoma. J Hepatol 2013(58):3

    Google Scholar 

  • El-Serag HB (2001) Epidemiology of hepatocellular carcinoma. Clin Liver Dis 5(1):87–107, vi

  • El-Serag HB (2002) Hepatocellular carcinoma: an epidemiologic view. J Clin Gastroenterol 35(5 Suppl 2):S72–S78

    Article  PubMed  Google Scholar 

  • El-Serag HB (2004) Hepatocellular carcinoma: recent trends in the United States. Gastroenterology 127(5 Suppl 1):S27–S34

    Article  PubMed  Google Scholar 

  • El-Serag HB (2011) Hepatocellular carcinoma. N Engl J Med 365(12):1118–1127

    Article  CAS  PubMed  Google Scholar 

  • El-Serag HB, Davila JA (2011) Surveillance for hepatocellular carcinoma: in whom and how? Therap Adv Gastroenterol 4(1):5–10

    Article  PubMed Central  PubMed  Google Scholar 

  • Evan RJ, Kakati D, Shoreibah MG, Bloomer JR, Singal AK (2014) CT scans are overused for hepatocellular carcinoma screening in patients with cirrhosis. Gastroenterology 146(Suppl.), Abstract

  • Feng K, Yan J, Li X, Xia F, Ma K, Wang S et al (2012) A randomized controlled trial of radiofrequency ablation and surgical resection in the treatment of small hepatocellular carcinoma. J Hepatol 57(4):794–802

    Article  PubMed  Google Scholar 

  • Forner A, Vilana R, Ayuso C, Bianchi L, Sole M, Ayuso JR et al (2008) Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatology 47(1):97–104

    Article  PubMed  Google Scholar 

  • Forner A, Llovet JM, Bruix J (2012) Hepatocellular carcinoma. Lancet 379(9822):1245–1255

    Article  PubMed  Google Scholar 

  • Georgiades C, Geschwind JF, Harrison N, Hines-Peralta A, Liapi E, Hong K et al (2012) Lack of response after initial chemoembolization for hepatocellular carcinoma: does it predict failure of subsequent treatment? Radiology 265(1):115–123

    Article  PubMed Central  PubMed  Google Scholar 

  • Giorgio A, Tarantino L, de Stefano G, Coppola C, Ferraioli G (2005) Complications after percutaneous saline-enhanced radiofrequency ablation of liver tumors: 3-year experience with 336 patients at a single center. AJR Am J Roentgenol 184(1):207–211

    Article  PubMed  Google Scholar 

  • Hama Y, Kusano S (2005) Liver abscess formation after hepatic chemoembolization for metastatic pancreatic neuroendocrine tumor. Minim Invasive Ther Allied Technol 14(1):6–7

    Article  CAS  PubMed  Google Scholar 

  • Hsu KY, Chau GY, Lui WY, Tsay SH, King KL, Wu CW (2009) Predicting morbidity and mortality after hepatic resection in patients with hepatocellular carcinoma: the role of Model for End-Stage Liver Disease score. World J Surg 33(11):2412–2419

    Article  PubMed  Google Scholar 

  • Huang SF, Ko CW, Chang CS, Chen GH (2003) Liver abscess formation after transarterial chemoembolization for malignant hepatic tumor. Hepatogastroenterology 50(52):1115–1118

    PubMed  Google Scholar 

  • Huang K, Zhou Q, Wang R, Cheng D, Ma Y (2014) Doxorubicin-eluting beads versus convention transarterial chemoembolization for the treatment of hepatocellular carcinoma. J Gastroenterol Hepatol 25(5):920–925

    Article  CAS  Google Scholar 

  • Huo TI, Lin HC, Hsia CY, Wu JC, Lee PC, Chi CW et al (2007) The model for end-stage liver disease based cancer staging systems are better prognostic models for hepatocellular carcinoma: a prospective sequential survey. Am J Gastroenterol 102(9):1920–1930

    Article  PubMed  Google Scholar 

  • Imamura H, Matsuyama Y, Tanaka E, Ohkubo T, Hasegawa K, Miyagawa S et al (2003) Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol 38(2):200–207

    Article  PubMed  Google Scholar 

  • Ioannou GN, Perkins JD, Carithers RL Jr (2008) Liver transplantation for hepatocellular carcinoma: impact of the MELD allocation system and predictors of survival. Gastroenterology 134(5):1342–1351

    Article  PubMed  Google Scholar 

  • Jepsen P, Vilstrup H, Tarone RE, Friis S, Sorensen HT (2007) Incidence rates of hepatocellular carcinoma in the U.S. and Denmark: recent trends. Int J Cancer 121(7):1624–1626

    Article  CAS  PubMed  Google Scholar 

  • Jepsen P, Ott P, Andersen PK, Sorensen HT, Vilstrup H (2012) Risk for hepatocellular carcinoma in patients with alcoholic cirrhosis: a Danish nationwide cohort study. Ann Intern Med 156(12):841–847, W295

  • Johnson PJ, Qin S, Park JW, Poon RT, Raoul JL, Philip PA, Hsu CH, Hu TH, Heo J, Xu J, Lu L, Chao Y, Boucher E, Han KH, Paik SW, Robles-Aviña J, Kudo M, Yan L, Sobhonslidsuk A, Komov D, Decaens T, Tak WY, Jeng LB, Liu D, Ezzeddine R, Walters I, Cheng AL (2013) Brivanib versus sorafenib as first line therapy in patients with unresectable, advanced hepatocellular carcinoma: results from the randomized phase III BRISK-FL study. J Clin Oncol 31(28):3517–3524

    Article  CAS  PubMed  Google Scholar 

  • Kojiro M (2004) Focus on dysplastic nodules and early hepatocellular carcinoma: an Eastern point of view. Liver Transplant 10(2 Suppl 1):S3–S8

    Article  Google Scholar 

  • Kudo M (2011) Hepatocellular carcinoma in 2011 and beyond: from the pathogenesis to molecular targeted therapy. Oncology 81(Suppl 1):1–10

    Article  CAS  PubMed  Google Scholar 

  • Kudo M, Han G, Finn RS, Poon RT, Blanc JF, Yan L, Yang J, Lu L, Tak WY, Yu X, Lee JH, Lin SM, Wu C, Tanwandee T, Shao G, Walters IB, Dela Cruz C, Poulart V, Wang JH (2014) Brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: a randomized phase 3 trial. Hepatology. doi:10.1002/hep.27290

  • Lammer J, Malagari K, Vogl T, Pilleul F, Denys A, Watkinson A et al (2010) Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol 33(1):41–52

    Article  PubMed Central  PubMed  Google Scholar 

  • Lee JM, Yoon JH, Kim KW (2012) Diagnosis of hepatocellular carcinoma: newer radiological tools. Semin Oncol 39(4):399–409

    Article  PubMed  Google Scholar 

  • Levy I, Greig PD, Gallinger S, Langer B, Sherman M (2001) Resection of hepatocellular carcinoma without preoperative tumor biopsy. Ann Surg 234(2):206–209

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Liang W, Wang D, Ling X, Kao AA, Kong Y, Shang Y et al (2012) Sirolimus-based immunosuppression in liver transplantation for hepatocellular carcinoma: a meta-analysis. Liver Transplant 18(1):62–69

    Article  Google Scholar 

  • Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H et al (2004) Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 351(15):1521–1531

    Article  CAS  PubMed  Google Scholar 

  • Lim KC, Chow PK, Allen JC, Siddiqui FJ, Chan ES, Tan SB (2012) Systematic review of outcomes of liver resection for early hepatocellular carcinoma within the Milan criteria. Br J Surg 99(12):1622–1629

    Article  PubMed  Google Scholar 

  • Livraghi T, Meloni F, Di Stasi M, Rolle E, Solbiati L, Tinelli C et al (2008) Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: is resection still the treatment of choice? Hepatology 47(1):82–89

    Article  PubMed  Google Scholar 

  • Llovet JM, Bruix J (2003) Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 37(2):429–442

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Bruix J (2008) Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol 48(Suppl 1):S20–S37

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Fuster J, Bruix J (1999) Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 30(6):1434–1440

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Sala M, Castells L, Suarez Y, Vilana R, Bianchi L et al (2000) Randomized controlled trial of interferon treatment for advanced hepatocellular carcinoma. Hepatology 31(1):54–58

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Vilana R, Bru C, Bianchi L, Salmeron JM, Boix L et al (2001) Increased risk of tumor seeding after percutaneous radiofrequency ablation for single hepatocellular carcinoma. Hepatology 33(5):1124–1129

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX et al (2008a) Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst 100(10):698–711

    Article  PubMed  Google Scholar 

  • Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF et al (2008b) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359(4):378–390

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Decaens T, Raoul JL, Boucher E, Kudo M, Chang C, Kang YK, Assenat E, Lim HY, Boige V, Mathurin P, Fartoux L, Lin DY, Bruix J, Poon RT, Sherman M, Blanc JF, Finn RS, Tak WY, Chao Y, Ezzeddine R, Liu D, Walters I, Park JW (2013) Brivanib in patients with advanced hepatocellular carcinoma who were intolerant to sorafenib or for whom sorafenib failed: results from the randomized phase III BRISK-PS study. J Clin Oncol 31(28):3509–3516

    Article  CAS  PubMed  Google Scholar 

  • Maithel SK, Kneuertz PJ, Kooby DA, Scoggins CR, Weber SM, Martin RC, 2nd et al (2011) Importance of low preoperative platelet count in selecting patients for resection of hepatocellular carcinoma: a multi-institutional analysis. J Am Coll Surg 212(4), 638–648; discussion 648–650

  • Majno PE, Adam R, Bismuth H, Castaing D, Ariche A, Krissat J et al (1997) Influence of preoperative transarterial lipiodol chemoembolization on resection and transplantation for hepatocellular carcinoma in patients with cirrhosis. Ann Surg 226(6):688–701; discussion 701–683

  • Malagari K, Chatzimichael K, Alexopoulou E, Kelekis A, Hall B, Dourakis S et al (2008) Transarterial chemoembolization of unresectable hepatocellular carcinoma with drug eluting beads: results of an open-label study of 62 patients. Cardiovasc Intervent Radiol 31(2):269–280

    Article  PubMed  Google Scholar 

  • Manesis EK, Giannoulis G, Zoumboulis P, Vafiadou I, Hadziyannis SJ (1995) Treatment of hepatocellular carcinoma with combined suppression and inhibition of sex hormones: a randomized, controlled trial. Hepatology 21(6):1535–1542

    CAS  PubMed  Google Scholar 

  • Marrero JA, Su GL, Wei W, Emick D, Conjeevaram HS, Fontana RJ et al (2003) Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in American patients. Hepatology 37(5):1114–1121

    Article  CAS  PubMed  Google Scholar 

  • Massie AB, Caffo B, Gentry SE, Hall EC, Axelrod DA, Lentine KL et al (2011) MELD exceptions and rates of waiting list outcomes. Am J Transplant 11(11):2362–2371

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F et al (1996) Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334(11):693–699

    Article  CAS  PubMed  Google Scholar 

  • Mazzaferro V, Sposito C, Bhoori S, Romito R, Chiesa C, Morosi C, Maccauro M, Marchianò A, Bongini M, Lanocita R, Civelli E, Bombardieri E, Camerini T, Spreafico C (2013) Ytrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study. Hepatology 57(5):1826–1837

    Article  CAS  PubMed  Google Scholar 

  • Minagawa M, Makuuchi M, Takayama T, Kokudo N (2003) Selection criteria for repeat hepatectomy in patients with recurrent hepatocellular carcinoma. Ann Surg 238(5):703–710

    Article  PubMed Central  PubMed  Google Scholar 

  • Morimoto O, Nagano H, Sakon M, Fujiwara Y, Yamada T, Nakagawa H et al (2003) Diagnosis of intrahepatic metastasis and multicentric carcinogenesis by microsatellite loss of heterozygosity in patients with multiple and recurrent hepatocellular carcinomas. J Hepatol 39(2):215–221

    Article  CAS  PubMed  Google Scholar 

  • Mueller GC, Hussain HK, Carlos RC, Nghiem HV, Francis IR (2003) Effectiveness of MR imaging in characterizing small hepatic lesions: routine versus expert interpretation. AJR Am J Roentgenol 180(3):673–680

    Article  PubMed  Google Scholar 

  • National Comprehensive Cancer Network Guidelines. www.nccn.org

  • Naimark D, Naglie G, Detsky AS (1994) The meaning of life expectancy: what is a clinically significant gain? J Gen Intern Med 9(12):702–707

    Article  CAS  PubMed  Google Scholar 

  • Nerenstone SR, Ihde DC, Friedman MA (1988) Clinical trials in primary hepatocellular carcinoma: current status and future directions. Cancer Treat Rev 15(1):1–31

    Article  CAS  PubMed  Google Scholar 

  • Nicolini D, Svegliati-Baroni G, Candelari R, Mincarelli C, Mandolesi A, Bearzi I et al (2013) Doxorubicin-eluting bead vs conventional transcatheter arterial chemoembolization for hepatocellular carcinoma before liver transplantation. World J Gastroenterol 19(34):5622–5632

    Article  PubMed Central  PubMed  Google Scholar 

  • Nowak AK, Stockler MR, Chow PK, Findlay M (2005) Use of tamoxifen in advanced-stage hepatocellular carcinoma. A systematic review. Cancer 103(7):1408–1414

    Article  CAS  PubMed  Google Scholar 

  • Okada S (1999) Local ablation therapy for hepatocellular carcinoma. Semin Liver Dis 19(3):323–328

    Article  CAS  PubMed  Google Scholar 

  • Okuda K, Ohtsuki T, Obata H, Tomimatsu M, Okazaki N, Hasegawa H et al (1985) Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer 56(4):918–928

    Article  CAS  PubMed  Google Scholar 

  • Orlando A, Leandro G, Olivo M, Andriulli A, Cottone M (2009) Radiofrequency thermal ablation vs. percutaneous ethanol injection for small hepatocellular carcinoma in cirrhosis: meta-analysis of randomized controlled trials. Am J Gastroenterol 104(2):514–524

    Article  PubMed  Google Scholar 

  • Park YN, Kojiro M, Di Tommaso L, Dhillon AP, Kondo F, Nakano M et al (2007) Ductular reaction is helpful in defining early stromal invasion, small hepatocellular carcinomas, and dysplastic nodules. Cancer 109(5):915–923

    Article  PubMed  Google Scholar 

  • Park CW, Tsai NT, Wong LL (2011) Implications of worse renal dysfunction and medical comorbidities in patients with NASH undergoing liver transplant evaluation: impact on MELD and more. Clin Transplant 25(6):E606–E611

    Article  PubMed  Google Scholar 

  • Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55(2):74–108

    Article  PubMed  Google Scholar 

  • Pocha C, Dieperink E, McMaken KA, Knott A, Thuras P, Ho SB (2013) Surveillance for hepatocellular cancer with ultrasonography vs. computed tomography—a randomised study. Aliment Pharmacol Ther 38(3):303–312

    Article  CAS  PubMed  Google Scholar 

  • Pomfret EA, Washburn K, Wald C, Nalesnik MA, Douglas D, Russo M et al (2010) Report of a national conference on liver allocation in patients with hepatocellular carcinoma in the United States. Liver Transplant 16(3):262–278

    Article  Google Scholar 

  • Porta C, Paglino C (2010) Medical treatment of unresectable hepatocellular carcinoma: going beyond sorafenib. World J Hepatol 2(3):103–113

    PubMed Central  PubMed  Google Scholar 

  • Raoul JL, Guyader D, Bretagne JF, Duvauferrier R, Bourguet P, Bekhechi D et al (1994) Randomized controlled trial for hepatocellular carcinoma with portal vein thrombosis: intra-arterial iodine-131-iodized oil versus medical support. J Nucl Med 35(11):1782–1787

    CAS  PubMed  Google Scholar 

  • Robic MA, Procopet B, Metivier S, Peron JM, Selves J, Vinel JP et al (2011) Liver stiffness accurately predicts portal hypertension related complications in patients with chronic liver disease: a prospective study. J Hepatol 55(5):1017–1024

    Article  PubMed  Google Scholar 

  • Saab S, Ly D, Nieto J, Kanwal F, Lu D, Raman S et al (2003) Hepatocellular carcinoma screening in patients waiting for liver transplantation: a decision analytic model. Liver Transplant 9(7):672–681

    Article  Google Scholar 

  • Sala M, Fuster J, Llovet JM, Navasa M, Sole M, Varela M et al (2004) High pathological risk of recurrence after surgical resection for hepatocellular carcinoma: an indication for salvage liver transplantation. Liver Transplant 10(10):1294–1300

    Article  Google Scholar 

  • Salem R, Lewandowski RJ, Mulcahy MF, Riaz A, Ryu RK, Ibrahim S, Atassi B, Baker T, Gates V, Miller FH, Sato KT, Wang E, Gupta R, Benson AB, Newman SB, Omary RA, Abecassis M, Kulik L (2010) Radioembolization for hepatocellular carcinoma using Ytrium-90 microspheres: a comprehensive report of long-term outcomes. J Gastroenterol 138(1):52–64

    Article  CAS  Google Scholar 

  • Salem R, Lewandowski RJ, Kulik L, Wang E, Riaz A, Ryu RK et al (2011) Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology 140(2):497–507 e492

  • Salem R, Gilbertsen M, Butt Z, Memon K, Vouche M, Hickey R, Baker T, Abecassis MM, Atassi R, Riaz A, Cella D, Burns JL, Ganger D, Benson AB 3rd, Mulcahy MF, Kulik L, Lewandowski R (2013) Increased quality of life among hepatocellular carcinoma patients treated with radioembolization, compared with chemoembolization. Clin Gastroenterol Hepatol 11(10):1358–1365

    Article  PubMed  Google Scholar 

  • Santagostino E, Colombo M, Rivi M, Rumi MG, Rocino A, Linari S et al (2003) A 6-month versus a 12-month surveillance for hepatocellular carcinoma in 559 hemophiliacs infected with the hepatitis C virus. Blood 102(1):78–82

    Article  CAS  PubMed  Google Scholar 

  • Sarasin FP, Giostra E, Hadengue A (1996) Cost-effectiveness of screening for detection of small hepatocellular carcinoma in western patients with Child-Pugh class A cirrhosis. Am J Med 101(4):422–434

    Article  CAS  PubMed  Google Scholar 

  • Sarasin FP, Majno PE, Llovet JM, Bruix J, Mentha G, Hadengue A (2001) Living donor liver transplantation for early hepatocellular carcinoma: a life-expectancy and cost-effectiveness perspective. Hepatology 33(5):1073–1079

    Article  CAS  PubMed  Google Scholar 

  • Sato H, Maruta M, Kuromizu J, Utumi T, Touyama K, Takizawa K (1994) AFP-producing intestinal cancer. Nihon Rinsho Suppl 6:7–10

    CAS  PubMed  Google Scholar 

  • Sato M, Tateishi R, Yasunaga H, Horiguchi H, Yoshida H, Matsuda S et al (2012) Mortality and morbidity of hepatectomy, radiofrequency ablation, and embolization for hepatocellular carcinoma: a national survey of 54,145 patients. J Gastroenterol 47(10):1125–1133

    Article  PubMed  Google Scholar 

  • Schnitzbauer AA (2010) A prospective randomized, open-labeled trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing. BMC Cancer 1(10):190

    Article  CAS  Google Scholar 

  • Schwartz JD, Schwartz M, Mandeli J, Sung M (2002) Neoadjuvant and adjuvant therapy for resectable hepatocellular carcinoma: review of the randomised clinical trials. Lancet Oncol 3(10):593–603

    Article  PubMed  Google Scholar 

  • Sergio A, Cristofori C, Cardin R, Pivetta G, Ragazzi R, Baldan A et al (2008) Transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): the role of angiogenesis and invasiveness. Am J Gastroenterol 103(4):914–921

    Article  PubMed  Google Scholar 

  • Shen A, Tang C, Wang Y, Chen Y, Yan X, Zhang C et al (2013) A systematic review of sorafenib in Child-Pugh A patients with unresectable hepatocellular carcinoma. J Clin Gastroenterol 47(10):871–880

    Article  CAS  PubMed  Google Scholar 

  • Shirabe K, Kanematsu T, Matsumata T, Adachi E, Akazawa K, Sugimachi K (1991) Factors linked to early recurrence of small hepatocellular carcinoma after hepatectomy: univariate and multivariate analyses. Hepatology 14(5):802–805

    Article  CAS  PubMed  Google Scholar 

  • Silva MA, Hegab B, Hyde C, Guo B, Buckels JA, Mirza DF (2008) Needle track seeding following biopsy of liver lesions in the diagnosis of hepatocellular cancer: a systematic review and meta-analysis. Gut 57(11):1592–1596

    Article  CAS  PubMed  Google Scholar 

  • Singal AK, Fontana RJ (2011) Oral antiviral agents reduce the risk of hepatocellular carcinoma in patients with chronic hepatitis B: systematic review and meta-analysis. Hepatology 54:1016A

    Google Scholar 

  • Singal A, Volk ML, Waljee A, Salgia R, Higgins P, Rogers MA et al (2009) Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis. Aliment Pharmacol Ther 30(1):37–47

    Article  CAS  PubMed  Google Scholar 

  • Singal AK, Freeman DH, Anand BS (2010a) Meta-analysis: interferon improves outcomes following ablation or resection of hepatocellular carcinoma. Aliment Pharmacol Ther 32(7):851–858

    Article  CAS  PubMed  Google Scholar 

  • Singal AK, Singh A, Jaganmohan S, Guturu P, Mummadi R, Kuo YF et al (2010b) Antiviral therapy reduces risk of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis. Clin Gastroenterol Hepatol 8(2):192–199

    Article  PubMed  Google Scholar 

  • Singal AG, Pillai A, Tiro J (2014) Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis. PLoS Med 11(4):e1001624

    Article  PubMed Central  PubMed  Google Scholar 

  • Teh SH, Christein J, Donohue J, Que F, Kendrick M, Farnell M et al (2005) Hepatic resection of hepatocellular carcinoma in patients with cirrhosis: Model of End-Stage Liver Disease (MELD) score predicts perioperative mortality. J Gastrointest Surg 9(9):1207–1215; discussion 1215

  • Toso C, Merani S, Bigam DL, Shapiro AM, Kneteman NM (2010) Sirolimus-based immunosuppression is associated with increased survival after liver transplantation for hepatocellular carcinoma. Hepatology 51(4):1237–1243

    Article  CAS  PubMed  Google Scholar 

  • Toso C, Dupuis-Lozeron E, Majno P, Berney T, Kneteman NM, Perneger T et al (2012) A model for dropout assessment of candidates with or without hepatocellular carcinoma on a common liver transplant waiting list. Hepatology 56(1):149–156

    Article  PubMed  Google Scholar 

  • Trevisani F, D’Intino PE, Morselli-Labate AM, Mazzella G, Accogli E, Caraceni P et al (2001) Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status. J Hepatol 34(4):570–575

    Article  CAS  PubMed  Google Scholar 

  • Trevisani F, De NS, Rapaccini G, Farinati F, Benvegnu L, Zoli M et al (2002) Semiannual and annual surveillance of cirrhotic patients for hepatocellular carcinoma: effects on cancer stage and patient survival (Italian experience). Am J Gastroenterol 97(3):734–744

    Article  PubMed  Google Scholar 

  • Trotter JF, Wachs M, Everson GT, Kam I (2002) Adult-to-adult transplantation of the right hepatic lobe from a living donor. N Engl J Med 346(14):1074–1082

    Article  PubMed  Google Scholar 

  • Ulahannan SV, Duffy AG, McNeel TS, Kish JK, Dickie LA, Rahma OE et al (2014) Earlier presentation and application of curative treatments in hepatocellular carcinoma. Hepatology. doi:10.1002/hep.27288

  • Varela M, Real MI, Burrel M, Forner A, Sala M, Brunet M et al (2007) Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol 46(3):474–481

    Article  CAS  PubMed  Google Scholar 

  • Vauthey JN, Lauwers GY, Esnaola NF, Do KA, Belghiti J, Mirza N et al (2002) Simplified staging for hepatocellular carcinoma. J Clin Oncol 20(6):1527–1536

    Article  PubMed  Google Scholar 

  • Washburn K, Edwards E, Harper A, Freeman R (2010) Hepatocellular carcinoma patients are advantaged in the current liver transplant allocation system. Am J Transplant 10(7):1643–1648

    Article  CAS  PubMed  Google Scholar 

  • Welch J, Shukla R, Igbo NL, Singal AK, Kazan-Tannus JF, Soloway RD (2010) Use of ultrasound as initial imaging exam for hepatocellular carcinoma in high risk populations. Gastroenterology (Suppl.):S219

  • Wiesner RH, Freeman RB, Mulligan DC (2004) Liver transplantation for hepatocellular cancer: the impact of the MELD allocation policy. Gastroenterology 127(5 Suppl 1):S261–S267

    Article  PubMed  Google Scholar 

  • Winslow E, Hawkins WG (2013) Laparoscopic resection of the liver for cancer. Surg Oncol Clin N Am 22(1):75–89

    Article  PubMed  Google Scholar 

  • Wu CY, Chen YJ, Ho HJ, Hsu YC, Kuo KN, Wu MS et al (2012) Association between nucleoside analogues and risk of hepatitis B virus-related hepatocellular carcinoma recurrence following liver resection. JAMA 308(18):1906–1914

    Article  CAS  PubMed  Google Scholar 

  • Xu G, Qi FZ, Zhang JH, Cheng GF, Cai Y, Miao Y (2012) Meta-analysis of surgical resection and radiofrequency ablation for early hepatocellular carcinoma. World J Surg Oncol 10:163

    Article  PubMed Central  PubMed  Google Scholar 

  • Yamasaki S, Hasegawa H, Kinoshita H, Furukawa M, Imaoka S, Takasaki K et al (1996) A prospective randomized trial of the preventive effect of pre-operative transcatheter arterial embolization against recurrence of hepatocellular carcinoma. Jpn J Cancer Res 87(2):206–211

    Article  CAS  PubMed  Google Scholar 

  • Yan S, Xu D, Sun B (2012) Combination of radiofrequency ablation with transarterial chemoembolization for hepatocellular carcinoma: a meta-analysis. Dig Dis Sci 57(11):3026–3031

    Article  CAS  PubMed  Google Scholar 

  • Yao FY, Bass NM, Nikolai B, Davern TJ, Kerlan R, Wu V et al (2002) Liver transplantation for hepatocellular carcinoma: analysis of survival according to the intention-to-treat principle and dropout from the waiting list. Liver Transplant 8(10):873–883

    Article  Google Scholar 

  • Zhang BH, Yang BH, Tang ZY (2004) Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol 130(7):417–422

    Article  PubMed  Google Scholar 

  • Zhang L, Hu P, Chen X, Bie P (2014) Transarterial chemoembolization (TACE) plus sorafenib versus TACE for intermediate or advanced stage hepatocellular carcinoma: a meta-analysis. PLoS One 9(6):e100305

  • Zimmerman MA, Ghobrial RM, Tong MJ, Hiatt JR, Cameron AM, Hong J et al (2008) Recurrence of hepatocellular carcinoma following liver transplantation: a review of preoperative and postoperative prognostic indicators. Arch Surg 143(2):182–188; discussion 188

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

We declare that we have no conflict of interests.

Author information

Authors and Affiliations

  1. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    P. Fitzmorris

  2. Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL, 35294-0012, USA

    M. Shoreibah & A. K. Singal

  3. Division of GI and Hepatology, Michael DeBakey VA Medical Center, Houston, TX, USA

    B. S. Anand

Authors
  1. P. Fitzmorris
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Shoreibah
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. S. Anand
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. K. Singal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. K. Singal.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fitzmorris, P., Shoreibah, M., Anand, B.S. et al. Management of hepatocellular carcinoma. J Cancer Res Clin Oncol 141, 861–876 (2015). https://doi.org/10.1007/s00432-014-1806-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-014-1806-0

Keywords

Search

Navigation