Hepatocellular carcinoma

Josep M. Llovet*, Robin Kate Kelley, Augusto Villanueva, Amit G. Singal, Eli Pikarsky, Sasan Roayaie, Riccardo Lencioni, Kazuhiko Koike, Jessica Zucman-Rossi, Richard S. Finn

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

2802 Scopus citations


Liver cancer remains a global health challenge, with an estimated incidence of >1 million cases by 2025. Hepatocellular carcinoma (HCC) is the most common form of liver cancer and accounts for ~90% of cases. Infection by hepatitis B virus and hepatitis C virus are the main risk factors for HCC development, although non-alcoholic steatohepatitis associated with metabolic syndrome or diabetes mellitus is becoming a more frequent risk factor in the West. Moreover, non-alcoholic steatohepatitis-associated HCC has a unique molecular pathogenesis. Approximately 25% of all HCCs present with potentially actionable mutations, which are yet to be translated into the clinical practice. Diagnosis based upon non-invasive criteria is currently challenged by the need for molecular information that requires tissue or liquid biopsies. The current major advancements have impacted the management of patients with advanced HCC. Six systemic therapies have been approved based on phase III trials (atezolizumab plus bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab) and three additional therapies have obtained accelerated FDA approval owing to evidence of efficacy. New trials are exploring combination therapies, including checkpoint inhibitors and tyrosine kinase inhibitors or anti-VEGF therapies, or even combinations of two immunotherapy regimens. The outcomes of these trials are expected to change the landscape of HCC management at all evolutionary stages.

Original languageAmerican English
Article number6
JournalNature Reviews Disease Primers
Issue number1
StatePublished - 21 Jan 2021

Bibliographical note

Funding Information:
J.M.L. receives research support from Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Boehringer-Ingelheim, Eisai Inc., and Ipsen and received consulting fees from AstraZeneca, Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Can-Fite Biopharma, Celsion Corporation, Eli Lilly, Eisai Inc., Exelixis, Genentech, Glycotest, Merck, Nucleix and Roche. R.K.K. receives research support to the institution from Adaptimmune, Agios Inc., AstraZeneca, Bayer, Bristol-Myers Squibb, Eli Lilly, EMD Serono, Exelixis, Merck, Novartis, Partner Therapeutics, QED and Taiho; R.K.K. has received consulting for Independent Data Monitoring Committee fees from Genentech or Roche and Gilead, and travel support from Ipsen. A.V. has received consulting fees from Guidepoint and Fujifilm and advisory board fees from Exact Sciences, Gilead, Nucleix and NGM Pharmaceuticals. A.G.S. has received consulting fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Exact Sciences, Exelixis, Fujifilm, Genentech, Glycotest, GRAIL and Roche. S.R. is a consulting director and a course director for Medtronic. R.L. reports advisory fees from AstraZeneca, Celsion and Guerbet. K.K. is receiving support from AbbVie GK, Asuka Pharmaceutical, Astellas, Bristol-Myers Squibb, Dainippon-Sumitomo Pharma, EA Pharma, Eisai Inc., Gilead Sciences, Merck, Otsuka Pharmaceuticals, Shionogi and Takeda Pharmaceuticals. R.S.F. reports consulting fees from AstraZeneca, Bayer, Bristol-Myers Squibb, CStone, Eisai, Eli Lilly, Merck, Novartis, Pfizer and Roche/Genentech. All other authors declare no competing interests.

Funding Information:
The authors thank Florian Castet for his invaluable support in the production of this manuscript. J.M.L. acknowledges his research funding from the Accelerator Award (HUNTER, Ref. C9380/A26813, partnership between the CRUK, AECC and AIRC), National Cancer Institute (P30-CA196521), U.S. Department of Defense (CA150272P3), Samuel Waxman Cancer Research Foundation, Spanish National Health Institute (PID2019-105378RB-100) and the Generalitat de Catalunya/AGAUR (SGR-1358). E.P. acknowledges his grants from the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation and the Israel Science Foundation.

Publisher Copyright:
© 2021, Springer Nature Limited.


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