Skip to main content
SpringerLink
Log in

Hepatocellular Cancer

  • Chapter
  • First Online:
Practical Medical Oncology Textbook

Part of the book series: UNIPA Springer Series ((USS))

Abstract

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults, and currently it still remains third leading cause of cancer death.

HCC affects patients’ chronic liver inflammation or cirrhosis, and it is most strictly associated to chronic viral hepatitis infection (such as hepatitis B or C) or exposure to alcohol or aflatoxin. Actually, metabolic syndrome and NASH are also increasingly recognized as risk factors for HCC.

Treatment and prognosis of HCC vary depending on the particulars of tumor size, number of hepatic lesions, and metastatization, even if patient Child-Pugh classification can change the treatment and especially the prognosis.

Localized and locally advanced settings are still based on resection, liver transplantation, ablation, and transcatheter arterial chemoembolization. Several improvements have been achieved in advanced and metastatic setting. Even if for the last 10 years, sorafenib was the only therapeutic strategy, nowadays new tyrosine kinase inhibitors and immune checkpoint inhibitors improved the survival of HCC patients.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Llovet JM, Ducreux M, Lencioni R, et al. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. Eur J Cancer. 2012;48:599–641.

    Article  Google Scholar 

  2. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012;379:1245–55.

    Article  PubMed  Google Scholar 

  3. El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365:1118–27.

    Article  CAS  PubMed  Google Scholar 

  4. Mittal S, El-Serag HB. Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol. 2013;47:S2–6.

    Article  PubMed  PubMed Central  Google Scholar 

  5. El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med. 1999;340:745–50.

    Article  CAS  PubMed  Google Scholar 

  6. Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.

    Article  PubMed  Google Scholar 

  7. Kumar V, Abbas AK, Fausto N, et al. Robbins and cotran pathologic basis of disease. 7th ed. Philadelphia: Elsevier Saunders; 2004.

    Google Scholar 

  8. Zhang DY, Friedman SL. Fibrosis-dependent mechanisms of hepatocarcinogenesis. Hepatology. 2012;56:769–75.

    Article  CAS  PubMed  Google Scholar 

  9. Nomura A, Stemmermann GN, Wasnich RD. Presence of hepatitis B surface antigen before primary hepatocellular carcinoma. JAMA. 1982;247:2247–9.

    Article  CAS  PubMed  Google Scholar 

  10. Tsukuma H, Hiyama T, Oshima A, et al. A case-control study of hepatocellular carcinoma in Osaka. Japan. Int J Cancer. 1990;45:231–6.

    Article  CAS  PubMed  Google Scholar 

  11. Beasley RP, Hwang LY, Lin CC, et al. Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22707 men in Taiwan. Lancet. 1981;2:1129–33.

    Article  CAS  PubMed  Google Scholar 

  12. Trichopoulos D. Hepatitis B virus and hepatocellular carcinoma. Lancet. 1979;8127:1192.

    Article  Google Scholar 

  13. Tabor E. Hepatitis C virus and hepatocellular carcinoma. AIDS Res Hum Retrovir. 1992;5:793–6.

    Google Scholar 

  14. Tabor E, Kobayashi K. Hepatitis C virus, a causative infectious agent of non-A, non-B hepatitis: prevalence and structure--summary of a conference on hepatitis C virus as a cause of hepatocellular carcinoma. J Natl Cancer Inst. 1992;84:86–90.

    Article  CAS  PubMed  Google Scholar 

  15. Zavitsanos X, Hatzakis A, Kaklamani E, et al. Association between hepatitis C virus and hepatocellular carcinoma using assays based on structural and nonstructural hepatitis C virus peptides. Cancer Res. 1992;52:5364–7.

    CAS  PubMed  Google Scholar 

  16. Peers FG, Linsell CA. Dietary aflatoxins and human primary liver cancer. Ann Nutr Aliment. 1977;31:1005–17.

    CAS  PubMed  Google Scholar 

  17. Franco D, Capussotti L, Smadja C, et al. Resection of hepatocellular carcinomas. Results in 72 European patients with cirrhosis. Gastroenterology. 1990;98:733–8.

    Article  CAS  PubMed  Google Scholar 

  18. Anthony PP. Primary carcinoma of the liver: a study of 282 cases in Ugandan Africans. J Pathol. 1973;110:37–48.

    Article  CAS  PubMed  Google Scholar 

  19. Bolondi L, Sofia S, Siringo S, et al. Surveillance programme of cirrhotic patients for early diagnosis and treatment of HCC: a cost effectiveness analysis. Gut. 2001;48:251–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sangiovanni A, Del Ninno E, Fasani P, et al. Increased survival of cirrhotic patients with a hepatocellular carcinoma detected during surveillance. Gastroenterology. 2004;126:1005–14.

    Article  PubMed  Google Scholar 

  21. Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391:1301–14.

    Article  PubMed  Google Scholar 

  22. Tanaka M, Nakashima O, Wada Y, Kage M, Kojiro M. Pathomorphological study of Kupffer cells in hepatocellular carcinoma and hyperplastic nodular lesions in the liver. Hepatology. 1996;24:807–12.

    Article  CAS  PubMed  Google Scholar 

  23. Hamilton SR, Aaltonen LA. Pathology and genetics of tumours of the digestive system. Lyon: IARC Press; 2000.

    Google Scholar 

  24. Bruix J, Reig M, Sherman M. Evidence-based diagnosis, staging, and treatment of patients with hepatocellular carcinoma. Gastroenterology. 2016;150:836–53.

    Article  Google Scholar 

  25. Wakabayashi G, Cherqui D, Geller DA, et al. Recommendations for laparoscopic liver resection: a report from the second international consensus conference held in Morioka. Ann Surg. 2015;261:619–29.

    PubMed  Google Scholar 

  26. Giulianotti PC, Bianco FM, Daskalaki D, et al. Robotic liver surgery: technical aspects and review of the literature. Hepatobiliary Surg Nutr. 2016;5:311–21.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Rahnemai-Azar AA, Cloyd JM, Weber SM, et al. Update on liver failure following hepatic resection: strategies for prediction and avoidance of post-operative liver insufficiency. J Clin Transl Hepatol. 2018;6:1–8.

    Article  Google Scholar 

  28. Chan J, Perini M, Fink M, et al. The outcomes of central hepatectomy versus extended hepatectomy: a systematic review and meta-analysis. HPB. 2018;20:487–96.

    Article  PubMed  Google Scholar 

  29. Cieslak KP, Huisman F, Bais T, et al. Future remnant liver function as predictive factor for the hypertrophy response after portal vein embolization. Surgery. 2017;162:37–47.

    Article  PubMed  Google Scholar 

  30. de Baere T, Teriitehau C, Deschamps F, et al. Predictive factors for hypertrophy of the future remnant liver after selective portal vein embolization. Ann Surg Oncol. 2010;17:2081–9.

    Article  PubMed  Google Scholar 

  31. Rhaiem R, Piardi T, Chetboun M, et al. Portal inflow modulation by somatostatin after major liver resection. Ann Surg. 2017;276:e101–3.

    Google Scholar 

  32. Okajima C, Arii S, Tanaka S, et al. Prognostic role of Child-Pugh score 5 and 6 in hepatocellular carcinoma patients who underwent curative hepatic resection. Am J Surg. 2015;209:199–205.

    Article  PubMed  Google Scholar 

  33. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649–55.

    Article  CAS  PubMed  Google Scholar 

  34. Cieslak KP, Runge JH, Heger M, et al. New perspectives in the assessment of future remnant liver. Dig Surg. 2014;31:255–68.

    Article  PubMed  Google Scholar 

  35. Memeo R, De Blasi V, Adam R, et al. Parenchymal-sparing hepatectomies (PSH) for bilobar colorectal liver metastases are associated with a lower morbidity and similar oncological results: a propensity score matching analysis. HPB. 2016;18:781–90.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Pauli EM, Staveley-O’Carroll KF, Brock MV, et al. A handy tool to teach segmental liver anatomy to surgical trainees. Arch Surg. 2012;147:692–3.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Memeo R, De’Angelis N, Compagnon P, et al. Laparoscopic vs. open liver resection for hepatocellular carcinoma of cirrhotic liver: a case-control study. World J Surg. 2014;38:11.

    Article  Google Scholar 

  38. Huang X, Lu S. A meta-analysis comparing the effect of anatomical resection vs. non-anatomical resection on the long-term outcomes for patients undergoing hepatic resection for hepatocellular carcinoma. HPB. 2017;19:843–9.

    Article  PubMed  Google Scholar 

  39. Appéré F, Piardi T, Memeo R, et al. Comparative study with propensity score matching analysis of two different methods of transection during hemi-right hepatectomy: Ultracision Harmonic Scalpel versus Cavitron Ultrasonic Surgical Aspirator. Surg Innov. 2017;24:5.

    Article  Google Scholar 

  40. Sotiropoulos GC, Prodromidou A, Kostakis ID, et al. Meta-analysis of laparoscopic vs open liver resection for hepatocellular carcinoma. Updat Surg. 2017;69:291–311.

    Article  Google Scholar 

  41. Byam J, Renz J, Millis JM. Liver transplantation for hepatocellular carcinoma. Hepatobiliary Surg Nutr. 2013;2:22–30.

    PubMed  PubMed Central  Google Scholar 

  42. Silva MF, Sherman M. Criteria for liver transplantation for HCC: what should the limits be? J Hepatol. 2011;55:1137–47.

    Article  PubMed  Google Scholar 

  43. Cherqui D, Laurent A, Mocellin N, et al. Liver resection for transplantable hepatocellular carcinoma: long-term survival and role of secondary liver transplantation. Ann Surg. 2009;250:5.

    Article  Google Scholar 

  44. Parikh ND, Waljee AK, Singal AG, et al. Downstaging hepatocellular carcinoma: a systematic review and pooled analysis. Liver Transpl. 2015;21:1142–52.

    Article  PubMed  Google Scholar 

  45. deLemos AS, Vagefi PA. Expanding the donor pool in liver transplantation: extended criteria donors. Clin Liver Dis. 2013;2:156–9.

    Article  Google Scholar 

  46. Salvalaggio PR, Felga GE, Guardia BD, et al. Time of dropout from the liver transplant list in patients with hepatocellular carcinoma: clinical behavior according to tumor characteristics and severity of liver disease. Transplant Proc. 2016;48:2319–22.

    Article  CAS  PubMed  Google Scholar 

  47. Facciorusso A, Serviddio G, Muscatiello N. Local ablative treatments for hepatocellular carcinoma: an updated review. World J Gastrointest Pharmacol Ther. 2016;7:477.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Luo W, Zhang Y, He G, et al. Effects of radiofrequency ablation versus other ablating techniques on hepatocellular carcinomas: a systematic review and meta-analysis. World J Surg Oncol. 2017;15:126.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Rhim H, Lim HK. Radiofrequency ablation of hepatocellular carcinoma: pros and cons. Gut Liver. 2010;1(Suppl 1):S113–8.

    Article  Google Scholar 

  50. Yang W, Yan K, Goldberg SN, et al. Ten-year survival of hepatocellular carcinoma patients undergoing radiofrequency ablation as a first-line treatment. World J Gastroenterol. 2016;22:2993–3005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Lee S, Kang TW, Cha DI, et al. Radiofrequency ablation vs. surgery for perivascular hepatocellular carcinoma: propensity score analyses of long-term outcomes. J Hepatol. 2018;69:70–8.

    Article  CAS  PubMed  Google Scholar 

  52. Dou J-P, Yu J, Yang X-H, et al. Outcomes of microwave ablation for hepatocellular carcinoma adjacent to large vessels: a propensity score analysis. Oncotarget. 2017;8:28758–68.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Vietti Violi N, Duran R, Guiu B, et al. Efficacy of microwave ablation versus radiofrequency ablation for the treatment of hepatocellular carcinoma in patients with chronic liver disease: a randomised controlled phase 2 trial. Lancet Gastroenterol Hepatol. 2018;3:317–25.

    Article  PubMed  Google Scholar 

  54. Gnoni A, Santini D, Scartozzi M, et al. Hepatocellular carcinoma treatment over sorafenib: epigenetics, microRNAs and microenvironment. Is there a light at the end of the tunnel? Expert Opin Ther Targets. 2015;19:1623–35.

    Article  CAS  PubMed  Google Scholar 

  55. Longo V, Brunetti O, Gnoni A, et al. Angiogenesis in pancreatic ductal adenocarcinoma: a controversial issue. Oncotarget. 2016;7:58649–58.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.

    Article  CAS  PubMed  Google Scholar 

  57. Cheng AL, Kang YK, Chen Z, 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.

    Article  CAS  PubMed  Google Scholar 

  58. Casadei Gardini A, Scarpi E, Marisi G, et al. Early onset of hypertension and serum electrolyte changes as potential predictive factors of activity in advanced HCC patients treated with sorafenib: results from a retrospective analysis of the HCC-AVR group. Oncotarget. 2016a;12:15243–51.

    Article  Google Scholar 

  59. Di Costanzo GG, Casadei Gardini A, Marisi G, et al. Validation of a simple scoring system to predict sorafenib effectiveness in patients with hepatocellular carcinoma. Target Oncol. 2017;6:795–803.

    Article  Google Scholar 

  60. Brunetti O, Gnoni A, Licchetta A, et al. Predictive and prognostic factors in HCC patients treated with sorafenib. Medicina (Kaunas). 2019;55:pii: E707.

    Article  Google Scholar 

  61. Casadei Gardini A, Scarpi E, Faloppi L, et al. Immune inflammation indicators and implication for immune modulation strategies in advanced hepatocellular carcinoma patients receiving sorafenib. Oncotarget. 2016b;41:67142–9.

    Article  Google Scholar 

  62. Faloppi L, Bianconi M, Memeo R, et al. Lactate dehydrogenase in hepatocellular carcinoma: something old, something new. Biomed Res Int. 2016;2016:7196280.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391:1163–73.

    Article  CAS  PubMed  Google Scholar 

  64. Cheng A-L, Qin S, Ikeda M, et al. IMbrave150: efficacy and safety results from a Ph 3 study evaluating ATEZOLIZUMAB (atezo) + bevacizumab (bev) vs sorafenib (sor) as first treatment (tx) for patients (pts) with unresectable hepatocellular carcinoma (HCC). Ann Oncol. 2019;30(9):ix186–7.

    Article  Google Scholar 

  65. Bruix J, Qin S, Merle P, Granito A, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389:56–66.

    Article  CAS  PubMed  Google Scholar 

  66. Abou-Alfa GK, Cheng A-L, et al. Phase 3 randomized, double-blind, controlled study of cabozantinib (XL184) versus placebo in subjects with hepatocellular carcinoma who have received prior sorafenib (CELESTIAL; NCT01908426). J Clin Oncol. 2014;32(5s (suppl)):abstr TPS4150.

    Article  Google Scholar 

  67. Zhu AX, Kang YK, Yen CJ, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20:282–96.

    Article  CAS  PubMed  Google Scholar 

  68. Longo V, Gnoni A, Casadei Gardini A, et al. Immunotherapeutic approaches for hepatocellular carcinoma. Oncotarget. 2017;8:33897–910.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. U.O.D. Chirurgia Epatobiliopancreatica, Ospedale “F. Miulli”, Acquaviva delle Fonti, Bari, Italy

    Riccardo Memeo

  2. Institut Hospitalo-Universitaire (IHU), Institute for Minimally Invasive Hybrid Image-Guided Surgery, Université de Strasbourg, Strasbourg, France

    Patrick Pessaux

  3. Medical Oncology Unit, Istituto Tumori “Giovanni Paolo II”, Bari, Italy

    Nicola Silvestris & Oronzo Brunetti

  4. Department of Internal Medicine and Oncology, University of Bari, Bari, Italy

    Nicola Silvestris & Antonio Giovanni Solimando

  5. Department of Medical Oncology, UNIMORE, Modena, Italy

    Andrea Casadei Gardini

Authors
  1. Riccardo Memeo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patrick Pessaux
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nicola Silvestris
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Oronzo Brunetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Antonio Giovanni Solimando
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andrea Casadei Gardini
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy

    Antonio Russo

  2. Oncology Department, University of Antwerp, Edegem, Belgium

    Marc Peeters

  3. Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy

    Lorena Incorvaia

  4. Center for Thoracic Oncology, Tisch Cancer Institute, Mount Sinai System & Icahn School of Medicine, Mount Sinai, NY, USA

    Christian Rolfo

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Memeo, R., Pessaux, P., Silvestris, N., Brunetti, O., Solimando, A.G., Gardini, A.C. (2021). Hepatocellular Cancer. In: Russo, A., Peeters, M., Incorvaia, L., Rolfo, C. (eds) Practical Medical Oncology Textbook. UNIPA Springer Series. Springer, Cham. https://doi.org/10.1007/978-3-030-56051-5_42

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-56051-5_42

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-56050-8

  • Online ISBN: 978-3-030-56051-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation