Hepatocellular Carcinoma: A Review
Main Article Content
Keywords
Barcelona clinic liver cance, checkpoint inhibitors, hepatocellular carcinoma, liver transplantation
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Chronic liver disease due to viral hepatitis, alcohol, non-alcoholic fatty liver disease, etc are risk factors for HCC development. Triphasic contrast-enhanced computed tomography (CECT) and magnetic resonance imaging (MRI) abdomen are modalities for HCC diagnosis best for lesions >2 cm size. For lesions <2 cm size, liquid biopsy with the determination of cell-free DNA in the blood is a newly emerging technique for diagnosis as well as for the planning of molecular targeted therapy. With the new concept of “Treatment stage migration”, the updated Barcelona clinic liver cancer (BCLC) algorithm for HCC management allows the best treatment modality for an individual patient. In addition to definitive therapy of resection and liver transplantation, palliative therapies like ablation, transarterial embolization, and others can be used. Among molecular targeted therapies for advanced BCLC stage C HCC, lenvatinib as first line, regorafenib and cabozantinib as second line therapy have been approved recently. The checkpoint inhibitors (CPIs), nivolumab and pembrolizumab, have revolutionized oncology practice in other solid organ cancers and have shown promising results in HCC management.
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11. Schulze K, Imbeaud S, Letouzé E, Alexandrov LB, Calderaro J, Rebouissou S, et al. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets. Nat Genet. 2015;47:505–11. https://doi. org/10.1038/ng.3252
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15. Wheeler DA. Comprehensive and integrative genomic characterization of hepatocellular carcinoma. Cell. 2017;169:1327–41. https://doi.org/10.1016/j.cell.2017.05.046
16. Sia D, Jiao Y, Martinez-Quetglas I, Schwartz M, Villanueva A, Llovet JM. Identification of an immune-specific class of hepatocellular carcinoma, based on molecular features. Gastroenterology. 2017;153:812–26. https://doi.org/10.1053/j. gastro.2017.06.007
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18. Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, Abecassis MM, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68:723–50. https://doi.org/10.1002/hep.29913
19. Park HJ, Jang HY, Kim SY, Lee SJ, Won HJ, Byun JH, et al. Non-enhanced magnetic resonance imaging as a surveillance tool for hepatocellular carcinoma: Comparison with ultrasound. J Hepatol. 2020;72:718–24. https://doi.org/10.1016/j. jhep.2019.12.001
20. Labgaa I, Villacorta-Martin C, D’Avola D, Craig AJ, von Felden J, Martins-Filho SN, et al. A pilot study of ultra-deep targeted sequencing of plasma DNA identifies driver mutations in hepatocellular carcinoma. Oncogene. 2018;37:3740–52. https://doi.org/10.1038/s41388-018-0206-3
21. Tommaso LD, Spadaccini M, Donadon M, Personeni N, Elamin A, Aghemo A, et al. Role of liver biopsy in hepatocellular carcinoma. World J Gastroenterol. 2019;25:6041–52. https:// doi.org/10.3748/wjg.v25.i40.6041
22. Wu X, Li J, Gassa A, Buchner D, Alakus H, Dong Q, et al. Circulating tumor DNA as an emerging liquid biopsy biomarker for early diagnosis and therapeutic monitoring in hepatocellular carcinoma. Int J Biol Sci. 2020;16:1551–62. https://doi. org/10.7150/ijbs.44024
23. Roberts LR, Sirlin CB, Zaiem F, Almasri J, Prokop LJ, Heimbach JK, et al. Imaging for the diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis. Hepatology. 2018;67:401–21. https://doi.org/10.1002/hep.29487
24. Chernyak V, Fowler KJ, Kamaya A, Kielar AZ, Elsayes KM, Bashir MR, et al. Liver Imaging Reporting and Data System (LI-RADS) version 2018: Imaging of hepatocellular carcinoma in at-risk patients. Radiology. 2018;289:816–30. https://doi. org/10.1148/radiol.2018181494
25. Llovet JM, Br. C, Bruix J. Prognosis of hepatocellular carcinoma: The BCLC staging classification. Semin Liver Dis. 1999;19:329–38. https://doi.org/10.1055/s-2007-1007122
26. The Cancer of the Liver Italian Program (CLIP) Investigators. A new prognostic system for hepatocellular carcinoma: A retrospective study of 435 patients. Hepatology. 1998;28:751–5. https://doi.org/10.1002/hep.510280322
27. Yau T, Tang VYF, Yao T-J, Fan S-T, Lo C-M, Poon RTP. Development of Hong Kong Liver Cancer staging system with treatment stratification for patients with hepatocellular carcinoma. Gastroenterology. 2014;146:1691–700. https://doi. org/10.1053/j.gastro.2014.02.032
28. Vitale A, Trevisani F, Farinati F, Cillo U. Treatment of hepatocellular carcinoma in the Precision Medicine era: From treatment stage migration to therapeutic hierarchy. Hepatology. 2020 Feb 16. doi: 10.1002/hep.31187. Epub ahead of print. https:// doi.org/10.1002/hep.31187
29. Kokudo T, Hasegawa K, Matsuyama Y, Takayama T, Izumi N, Kadoya M, et al. Liver Cancer Study Group of Japan. Survival benefit of liver resection for hepatocellular carcinoma associated with portal vein invasion. J Hepatol. 2016;65:938–43. https:// doi.org/10.1016/j.jhep.2016.05.044
30. Yin L, Li H, Li AJ, Lau WY, Pan ZY, Lai EC, et al. Partial hepatectomy vs. transcatheter arterial chemoembolization for resect-able multiple hepatocellular carcinoma beyond Milan Criteria: A RCT. J Hepatol. 2014;61:2–88. https://doi.org/10.1016/j. jhep.2014.03.012
31. Yao FY, Mehta N, Flemming J, Dodge J, Hameed B, Fix O, et al. Downstaging of hepatocellular cancer before liver transplant: Long-term outcome compared to tumors within Milan criteria. Hepatology. 2015;61:1968–77. https://doi.org/10.1002/hep.27752
32. Vitale A, Majno-Hurst P. Towards a personalized approach to hepatic resection in cirrhotic patients. J Hepatol. 2019;71:859– 61. https://doi.org/10.1016/j.jhep.2019.09.005
33. Prodeau M, Drumez E, Duhamel A, Vibert E, Farges O, Lassailly G, et al. An ordinal model to predict the risk of symptomatic liver failure in patients with cirrhosis undergoing hepatectomy. J Hepatol. 2019;71:920–9. https://doi.org/10.1016/j. jhep.2019.06.003
34. Roayaie S, Jibara G, Tabrizian P, Park JW, Yang J, Yan L, et al. The role of hepatic resection in the treatment of hepatocellular cancer. Hepatology. 2015;62:440–51. https://doi.org/10.1002/ hep.27745
35. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrho-sis. N Engl J Med. 1996;334:693–9. https://doi.org/10.1056/ NEJM199603143341104
36. Mazzaferro V, Sposito C, Zhou J, Pinna AD, Carlis LD, Fan J, et al. Metroticket 2.0 model for analysis of competing risks of death after liver transplantation for hepatocellular carcinoma. Gastroenterology. 2018;154(1):128–39. https://doi.org/10.1053/j. gastro.2017.09.025
37. Cucchetti A, Serenari M, Sposito C, Sandro SD, Mosconi C, Vicentin I, et al. Including mRECIST in the Metroticket 2.0 criteria improves prediction of hepatocellular carcinoma-related death after liver transplant. J Hepatol. 2020;73:342–8. https:// doi.org/10.1016/j.jhep.2020.03.018
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Sep 18, 2020
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Hepatocellular Carcinoma: A Review. (2020). Journal of Renal and Hepatic Disorders, 4(2), 51-60. https://doi.org/10.15586/jrenhep.v4i2.84
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Review Hepatology
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