Hepatocarcinoma. Epidemiology and diagnosis with a molecular approach
Hepatocarcinoma. Epidemiología y diagnóstico con enfoque molecular
Abstract
One of the greatest challenges faced by researchers in Hepatologyis the recognition of risk factors and predictors of the development of Hepatocarcinoma, in order to work on its prevention. Currently, the evidence is focused on the study of molecular factors of the tumor that allow demonstrating its ability to progress, to use them as predictive markers and even to classify them and thus establish therapeutic measures in early stages. Hepatocellular carcinoma (HCC) accounts for approximately 90% of all Primary Liver Cancer cases. It is the second leading cause of cancer-related death worldwide and has an incidence of 850,000 new cases per year. The main risk factors for developing HCC are well known and include infection by the hepatitis B and C viruses, Fatty Liver Disease due to Metabolic Dysfunction as it was recentlycalled, alcohol intake and ingestion of the fungal metabolite aflatoxin B1.Mutations have been identified during research on the molecular pathogenesis of HCC that even the most prevalent ones are not pharmacological targets. The molecular classificationof HCC has not yet been established and the BCLC -Barcelona Clinic Liver Cancer Classification is the main algorithm for stratifying patients according to prognosis and treatment assignment. Surveillance programs allow the detection of early-stage tumorsthat are amenable to curative therapies: resection, liver transplantation, or local ablation. To do this, biomarkers for therapy are investigated according to stratification, patient-adapted strategies aimed at driving mutations and / or activation of signaling cascades.
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Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2017; 67:358-380.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and Mortality: sources, methods, and major patters in GLOBOCAN 2012. Int J Cancer 2015;136: E359-E386.
Chiang CJ, Yang YW, You SL, Lai MS, Chen CJ. Thirty-year outcomes of the national hepatitis B immunization program in Taiwan. JAMA 2013; 310:974-976.
McCredie M, Williams S, Coates M. Cancer mortality in East and Southeast Asian migrants to New South Wales, Australia, 1975-1995. Br J Cancer 1999; 79:1277-1282.
Bosch FX, Ribes J, Díaz M, Cléries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology 2004;127: S5-S16.
Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53:1020-1022.
Chan AJ, Balderramo D, Kikuchi L, Ballerga EG, Prieto JE, Tapias M, et al. Early age hepatocellular carcinoma associated with hepatitis B infection in South America. Clin Gastroenterol Hepatol 2017; 15:1631-1632.
Pok S, Barn VA, Wong HJ, Blackburn AC, Board P, Farell GC, Teoh NC. Testosterone regulation of cyclin E kinase: a key factor in determining gender differences in hepatocarcinogenesis. J Gastroenterol Hepatol 2016; 31:1210-1219.
Petrick JL, Kelly SP, Altekruse SF, McGlynn KA, Rosenberg PS. Future of hepatocellular carcinoma incidence in the United States forecast through 2030. JClin Oncol 2016; 34:1787-1794.
Petrick JL, Braunlin M, Laversanne M, Valery PC, Bray F, McGlynn KA. International trends in liver cancer incidence, overall and by histologic subtype, 1978-2007. Int J Cancer 2016; 139:1534-1545.
Yang, D. et al. Impact of sex on the survival of patients with hepatocellular carcinoma: a Surveillance, Epidemiology, and End Results analysis. Cancer 120, 3707–3716 (2014).
Omer, R. E. et al. Population-attributable risk of dietary aflatoxins and hepatitis B virus infection with respect to hepatocellular carcinoma. Nutr. Cancer 48, 15–21 (2004).
Mittal, S. et al. Temporal trends of nonalcoholic fatty liver disease-related hepatocellular carcinoma in the veteran affairs population. Clin. Gastroenterol. Hepatol. 13, 594–601 e1 (2015).
Federico Piñero, Jaime Poniachik, Ezequiel Ridruejo, Marcelo Silva. Hepatocellular carcinoma in Latin America: Diagnosis and treatment challenges. World J Gastroenterol 2018 October 7; 24(37): 4224-4229
Méndez-Sánchez N, Ridruejo E, Alves de Mattos A, Chávez-Tapia NC, Zapata R, Paraná R, Mastai R, Strauss E, Guevara-Casallas LG, Daruich J, Gadano A, Parise ER, Uribe M, Aguilar-Olivos NE, Dagher L, Ferraz-Neto BH, Valdés-Sánchez M, Sánchez-Avila JF. Latin American Association for the Study of the Liver clinical practice guidelines: management of hepatocellular carcinoma. Ann Hepatol 2014;13 Suppl 1: S4–S40 [PMID 24998696]
Lizarzabal, Maribel et al. Manual Prevención, Vigilancia, Control y Tratamiento de Hepatitis Virales en Zulia- Venezuela. Available in www.amawebs.com/ storage/docs/h44bt47fcip.pdf
Lizarzábal (2006) /Dirección de Epidemiología y Análisis Estratégico/ Ministerio de Salud y Desarrollo Social (MSDS)2005. Gastroenterology in the New Century in Venezuela. A first five-year Situational Diagnosis. Inv Clinica 2007 48(Sup2):5-127
Domínguez E., Lizarzabal, M., Rangel R., Romero, G., Añez, M., Serrano, A., Latuff, Z., Fernandez, J. Hepatocarcinoma: epidemiología, características clínicas, de laboratorio y de imagen. Una revisión de 5 años. Annals of Hepatology 7(3):303. July-Sept 2008
León R, Domínguez M, Guzmán A, Martínez E, Roizental M. Abordaje terapéutico del HCC en Venezuela. ALEH 2012. Personal Communication
Josep M. Llovet, Jessica Zucman-Rossi, Eli Pikarsky , Bruno Sangro, Myron Schwartz , Morris Herman and Gregory Gores. Hepatocellular carcinoma. Nature Reviews Disease Primers. 2021; 7, Article number: 6.
Sarasin FP, Giostra E, Hadengue A. Cost-effectiveness of screening for detection of small hepatocellular carcinoma in western patients with Child-Pugh class A cirrhosis. Am J Med 1996; 101:422-434.
Lin OS, Keeffe EB, Sanders GD, Owens DK. Costeffectiveness of screening for hepatocellular carcinoma in patients with cirrhosis due to chronic hepatitis C. Aliment Pharmacol Ther. 2004; 19:1159-1172.
White DL, Richardson P, Tayoub N, Davila JA, Kanwal F, El-Serag HB. The updated model: an adjusted serum alpha-fetoprotein–based algorithm for hepatocellular carcinoma detection with hepatitis C virus-related cirrhosis. Gastroenterology 2015; 149:1986-1987.
Leerapun A, Suravarapu SV, Bida JP, Clark RJ, Sanders EL, Mettler TA, et al. The utility of Lens culinaris agglutinin-reactive alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: evaluation in a United States referral population. Cin Gastroenterol Hepatol 2007; 5:394-402.
Wallin R PH, Prydz H. Studies on a subcellular system for vitamin K-dependent carboxylation. Thromb Haemost 1979; 41:529-536.
Liebman HA, Furie BC, Tong MJ, Blanchard RA, Lo KJ, Lee SD, et al. Des-γ-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med 1984; 310:1427-1431.
Tsai SL, Huang GT, Yang PM, Sheu JC, Sung JL, Chen DS. Plasma des-gamma-carboxyprothrombin in the early stage of hepatocellular carcinoma. Hepatology 1990; 11:481-488
Taouli B, Hoshida Y, Kakite S, Chen X, Tan PS, Sun X, et al. Imaging-based surrogate markers of transcriptome subclasses and signatures in hepatocellular carcinoma: preliminary results. Eur Radiol 2017; 27:4472-4481
Nault, J.-C. et al. Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas. Nat. Genet. 10, 1187–93 (2015).
Zucman-Rossi, J., Villanueva, A., Nault, J.-C. & Llovet, J. M. The genetic landscape and biomarkers of hepatocellular carcinoma. Gastroenterology 5, 2015; 1226–1239.
32- Llovet, J. M. et al. A molecular signature to discriminate dysplastic nodules from early hepatocellular carcinoma in HCV cirrhosis. Gastroenterology. 2006; 131, 1758–67.
Wurmbach, E. et al. Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma. Hepatology. 2007; 45, 938–47.
Totoki, Y. et al. Trans-ancestry mutational landscape of hepatocellular carcinoma genomes. Nat. Genet. 2014; 46, 1267–73.
Di Tommaso, L. et al. Diagnostic value of HSP70, glypican 3, and glutamine synthetase in hepatocellular nodules in cirrhosis. Hepatology. 2007; 45, 725–34.
Di Tommaso, L. et al. The application of markers (HSP70 GPC3 and GS) in liver biopsies is useful for detection of hepatocellular carcinoma. J. Hepatol. 2009; 50, 746–54.
Günes, C. & Rudolph, K. L. The role of telomeres in stem cells and cancer. Cell 152, 390–3 (2013).
Satyanarayana, A. et al. Mitogen stimulation cooperates with telomere shortening to activate DNA damage responses and senescence signaling. Mol. Cell. Biol. 24, 5459–74 (2004).
Farazi, P. A. et al. Differential impact of telomere dysfunction on initiation and progression of hepatocellular carcinoma. Cancer Res. 63, 5021–7 (2003).
Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell. 2011; 144, 646–674.
Grivennikov, S. I., Greten, F. R. & Karin, M. Immunity, inflammation, and cancer. Cell. 2010; 140, 883–899.
Dvorak, H. F. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986; 315, 1650–1659
Hernandez-Gea, V., Toffanin, S., Friedman, S. L. & Llovet, J. M. Role of the microenvironment in the pathogenesis and treatment of hepatocellular carcinoma. Gastroenterology. 2013; 144, 512–527.
Crispe, I. N. The liver as a lymphoid organ. Annu Rev Immunol. 2009; 27, 147–163.
Pikarsky, E. et al. NF-kappaB functions as a tumour promoter in inflammationassociated cancer. Nature. 2004; 431, 461–6.
Bauer, J. et al. Lymphotoxin, NF-kB, and cancer: the dark side of cytokines. Dig Dis. 2012; 30, 453–468.
Taniguchi, K. & Karin, M. IL-6 and related cytokines as the critical lynchpins between inflammation and cancer. Semin Immunol. 2014; 26, 54–74.
Campbell, J. S. et al. Platelet-derived growth factor C induces liver fibrosis, steatosis, and hepatocellular carcinoma. Proc. Natl. Acad. Sci. 2005; U. S. A. 102, 3389–94.
Chen IP, Ariizumi -S, Nakano M, Yamamoto M. Positive glypican-3 expression in early hepatocellular carcinoma predicts recurrence after hepatectomy. JGastroenterol 2013; 49:117-125.
Tremosini S, Forner A, Boix L, Vilana R, Bianchi L, Reig M, et al. Prospective validation of an immunohistochemical panel (glypican 3, heat shock protein 70 and glutamine synthetase) in liver biopsies for diagnosis of very early hepatocellular carcinoma. Gut. 2012; 61:1481-1487
Lee, Y. A., Wallace, M. C. & Friedman, S. L. Pathobiology of liver fibrosis: a translational success story. Gut. 2015; 64, 830–41.
Elizabeth M. Brunt. Histopathologic Features of Hepatocellular Carcinoma. Clinical Liver Disease. 2012; Vol. 1, No. 6
Bruix J. Liver cancer: Still a long way to go. Hepatology 2011; 54:1-2.
Bruix J, Sherman M. Management of hepatocellular carcinoma: An update. Hepatology 2011; 53:1020-1022.
Parisi G. Should a radiological diagnosis of hepatocellular carcinoma be routinely confirmed by a biopsy? Yes. Eur J Intern Med 2012; 23:34-6.
Roncalli M, Park YN, Di Tommaso L. Histopathological classification of hepatocellular carcinoma. Dig Liver Dis 2010;42(suppl 3): S228-S234.
Wong, G. L.-H. et al. Accuracy of risk scores for patients with chronic hepatitis B receiving entecavir treatment. Gastroenterology. 2013; 144, 933–44.
Arends, P. et al. Entecavir treatment does not eliminate the risk of hepatocellular carcinoma in chronic hepatitis B: limited role for risk scores in Caucasians. Gut . 2015; 64, 1289–95.
Hugo A. Barrera-Saldana, Luis E. Fernández-Garzaa, Silvia A. Barrera-Barrera. Liquid biopsy in chronic liver disease. Annals of Hepatology. 2021; 20, 100-197.
Palmirotta R, Lovero D, Cafforio P, Felici C, Mannavola F, Pelle E, et al. Liquid biopsy of cancer: a multimodal diagnostic tool in clinical oncology. Ther Adv Med Oncol 2018; 10:1–24, https://doi.org/10.1177/175883591879463.
Yin CQ, Yuan CH, Qu Z, Guan Q, Chen H, Wang FB. Liquid biopsy of hepatocellular carcinoma: circulating tumor-derived biomarkers. Dis Mark 2016; 10:1–11, https://doi.org/10.1155/2016/1427849.
Wang J, Chang S, Li G, Sun Y. Application of liquid biopsy in precision medicine: opportunities and challenges. Front Med 2017; 11:522–7, https://doi.org/10.1007/s11684-017-0526-7.
Pinzani M. Liver Disease: Pathogenesis of Hepatic Fibrosis .American Association for the study of Liver Disease. 2006; 55 Annual Meeting. Boston. Pag.121-126.
García L, González F y Moreno R. 2012 ‟Cirrosis Hepática”. Medicine, 11(11):625-33.
Ripoll C, Bañares R. Cirrosis hepática. Medicine. 2008; 10(11):685-90.
Silva, M. A. et al. Needle track seeding following biopsy of liver lesions in the diagnosis of hepatocellular cancer: a systematic review and meta-analysis. Gut, 2008; 57, 1592–6
Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia. Hepatology. 2009; 49, 658–64.
Libbrecht, L. et al. Glypican-3 expression distinguishes small hepatocellular carcinomas from cirrhosis, dysplastic nodules, and focal nodular hyperplasia-like nodules. Am. J. Surg. Pathol. 2006; 30, 1405–11.
Tremosini, S. et al. Prospective validation of an immunohistochemical panel (glypican 3, heat shock protein 70 and glutamine synthetase) in liver biopsies for diagnosis of very early hepatocellular carcinoma. Gut. 2012; 61, 1481–7.
Zhang, H., Gao, C., Fang, L., Zhao, H.-C. & Yao, S.-K. Metformin and reduced risk of hepatocellular carcinoma in diabetic patients: a meta-analysis. Scand. J. Gastroenterol. 2013; 48, 78–87.
Zhang, X. et al. Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes. Hepatology. 2014; 60, 2008–16.