JCT  Vol.4 No.2 A , February 2013
Hepatocellular Carcinoma: Risk Factors, Diagnosis, Staging and Treatment in a Referral Centre
Abstract: Introduction: Hepatocellular carcinoma is the most common primary neoplasm of the liver and a significant cause of mortality in patients with cirrhosis. A retrospective cross-sectional study was performed to analyze epidemiological aspects related to risk factors, diagnosis, staging and first-line treatment in a closed population. Methods: The medical records of patients seen between November 1998 and May 2011 were revisited. Results: Of the 272 patients included in this study, 229 (84.2%) were male and the average age was 57.1 years (standard deviation 10.9 years). The most common etiology was hepatitis C virus infection in 145 (55.1%) patients, with this being the single cause in 88 (33.4%) patients. The largest masses ranged from 6 mm to 260 mm in diameter with a mean of 61.4 mm (standard deviation 41.5 mm). Only one mass was found in 145 (64.2%) cases, two masses in 26 (11.5%), three masses in 9 (4%) and 46 patients (20.3%) had multifocal disease. Early stage disease was diagnosed in 47 patients (22.0%), advanced stage in 65 (30.4%) and terminal stage in 32 (14.9%). Hepatocellular carcinoma was found by chance in 11%. Diagnosis was by means of imaging in 175 (68.1%) cases. The level of alpha-fetoprotein was measured in 209 patients, with 29.2% having levels lower than 20 ng/mL and 34.9% having levels above 400 ng/mL. Specific treatment was administered in 236 patients (86.8%) with hepatic chemoembolization in 127 (46.7%) and liver transplantation in 72 (26.5%); of these 33 (45.8%) received hepatic chemoembolization as a bridge to transplantation. Thirty-four patients (12.5%) received only supportive therapy. Conclusions: Patients are chiefly male and disease involvement generally occurs in the 5th decade of life. Cirrhosis was present in most patients and hepatitis C virus infection was the commonest etiologic agent. Only one imaging examination was required for diagnosis in most patients. The measurement of alpha-fetoprotein levels did not prove to be a good tool in the diagnosis of hepatocellular carcinoma. Intermediate, advanced and terminal stages predominated compared to early stages. Treatment was based on non-curative therapies.
Cite this paper: R. Raphe, W. Duca, P. Arroyo Jr., R. da Silva and R. da Silva, "Hepatocellular Carcinoma: Risk Factors, Diagnosis, Staging and Treatment in a Referral Centre," Journal of Cancer Therapy, Vol. 4 No. 2, 2013, pp. 384-393. doi: 10.4236/jct.2013.42A046.

[1]   J. F. Perz, G. L. Armstrong, L. A. Farrington, W. J. Hutin and B. F. Bell, “The Contributions of Hepatitis B Virus and Hepatitis C Infectious to Cirrhosis and Primary Liver Cancer Worldwide,” Journal of Hepatology, Vol. 45, No. 4, 2006, pp. 529-538. doi:10.1016/j.jhep.2006.05.013

[2]   F. B. Jemal, M. M. Center, J. Ferlay, E. Ward and D. Forman, “Global Cancer Statistics,” CA Cancer Journal of Clinical, Vol. 61, No. 2, 2011, pp. 69-90. doi:10.3322/caac.20107

[3]   S. F. Altekruse, K. A. McGlynn and M. E. Reichman, “Hepatocellular Carcinoma Incidence, Mortality, and Survival Trends in the United States from 1975 to 2005,” Journal of Clinical Oncololy, Vol. 27, No. 9, 2009, pp. 1485-1491. doi:10.1200/JCO.2008.20.7753

[4]   World Health Organization, International Agency for Research on Cancer, GLOBOCAN, 2008.

[5]   T. Y. M. Leong and A. S. Y. Leong, “Epidemiology and Carcinogenesis of Hepatocellular Carcinoma,” HPB (Oxford), Vol. 7, No. 1, 2007, pp. 5-15.

[6]   H. B. El-Serag, “Epidemiology of Hepatocellular Carcinoma in USA,” Hepatology Research, Vol. 37, No. S2, 2007, pp. S88-S94. doi:10.1111/j.1872-034X.2007.00168.x

[7]   S. Parikh and D. Hyman, “Hepatocellular Cancer: A Guide for the Internist,” American Journal of Medicine, Vol. 120, No. 3, 2007, pp.194-202. doi:10.1016/j.amjmed.2006.11.020

[8]   G. V. Papatheodoridis, P. Lampertico, S. Manolakopoulos and A. Lok, “Incidence of Hepatocellular Carcinoma in Chronic Hepatitis B Patients Receiving Nucleos(t)ide Therapy: A Systematic Review,” Journal of Hepatology, Vol. 53, No. 2, 2010, pp. 348-356. doi:10.1016/j.jhep.2010.02.035

[9]   G. L. Davis, M. J. Alter, H. El-Serag, T. Poynard and L. W. Jennings, “Aging of Hepatitis C Virus (HCV)-Infected persons in the United States: A Multiple Cohort Model of HCV Prevalence and Disease Progression,” Gastroenterology, Vol. 138, No. 2, 2010, pp. 513-521. doi:10.1053/j.gastro. 2009.09.067

[10]   E. E. Calle, C. Rodriguez, K. Walker-Thurmond and M. J. Thun, “Overweight, Obesity, and Mortality from Cancer in a Prospectively Studied Cohort of US Adults,” New England Journal of Medicine, Vol. 348, No. 17, 2003, pp. 1625-1638. doi:10.1056/NEJMoa021423

[11]   T. Ohki, R. Tateishi, T. Sato, J. Imamura, T. Goto, N. Yamashiki, H. Yoshida, F. Kato, S. Shiina, H. Yoshida, T. Kawabe and M. Omata, “Obesity Is an Independent Risk Factor for Hepatocellular Carcinoma Development in Chronic Hepatitis C Patients,” Clinical Gastroenterology and Hepatology, Vol. 6, No. 4, 2008, pp. 459-464. doi:10.1016/j.cgh.2008.02.012

[12]   B. Goodgame, N. J. Shaheen, J. Galanko and H. B. El-Serag, “The Risk of End Stage Liver Disease and Hepatocellular Carcinoma among Persons Infected with Hepatitis C Virus: Publication Bias?” American Journal of Gastroenterology, Vol. 98, No. 11, 2003, pp. 2535-2542. doi:10.1111/j.1572-0241.2003.07678.x

[13]   H. B. El-Serag, “Epidemiology of Viral Hepatitis and Hepatocellular Carcinoma,” Gastroenterology, Vol. 142, No. 5, 2012, pp. 1264-1273. doi:10.1053/j.gastro.2011.12.061

[14]   A. Forner, J. M. Llovet and J. Bruix, “Hepatocellular Carcinoma,” Lancet, Vol. 379, No. 9822, 2012, pp. 1245-1255. doi:10.1016/S0140-6736(11)61347-0

[15]   G. Fattovich, T. Stroffolini, I. Zagni and F. Donato, “Hepatocellular Carcinoma in Cirrhosis: Incidence and Risk Factors,” Gastroenterology, Vol. 127, No. 5, 2004, pp. S35-S50. doi:10.1053/j.gastro.2004.09.014

[16]   F. Donato, A. Tagger, U. Gelatti, G. Parrinello, P. Boffetta, A. Albertini, A. Decarli, P. Trevisi, M. L. Ribero, C. Martelli, S. Porru and G. Nardi, “Alcohol and Hepatocellular Carcinoma: The Effect of Lifetime Intake and Hepatitis Virus Infections in Men and Women,” American Journal of Epidemiology, Vol. 155, No. 4, 2002, pp. 323-331. doi:10.1093/aje/155.4.323

[17]   Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, “Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III),” Journal of the American Medical Association, Vol. 285, No. 19, 2001, pp. 2486- 2497. doi:10.1001/jama.285.19.2486

[18]   T. M. Welzel, B. I. Graubard, S. Zeuzem, H. B. El-Serag, J. A. Davila and K. A. McGlynn, “Metabolic Syndrome Increases the Risk of Primary Liver Cancer in the United States: A Study in the SEER-Medicare Database,” Hepatology, Vol. 54, No. 2, 2011, pp. 463-471. doi:10.1002/hep.24397

[19]   H. B. El-Serag, T. Tran and J. E. Everhart, “Diabetes Increases the Risk of Chronic Liver Disease and Hepatocellular Carcinoma,” Gastroenterology, Vol. 126, No. 2, 2004, pp. 460-468. doi:10.1053/j.gastro.2003.10.065

[20]   H. B. El-Serag, H. Hampel and F. Javadi, “The Association between Diabetes and Hepatocellular Carcinoma: A Systematic Review of Epidemiologic Evidence,” Clinical Gastroenterology and Hepatology, Vol. 4, No. 3, 2006, pp. 369-380. doi:10.1016/j.cgh.2005.12.007

[21]   M. S. Ascha, I. A. Hanouneh, R. Lopez, T. A. Tamimi, A. F. Feldstein and N. N. Zein, “The Incidence and Risk Factors of Hepatocellular Carcinoma in Patients with Nonalcoholic Steatohepatitis,” Hepatology, Vol. 51, No. 6, 2010, pp. 1972-1978. doi:10.1002/hep.23527

[22]   K. Yasui, E. Hashimoto, Y. Komorizono, K. Koike, S. Arii, Y. Imai, T. Shiima, Y. Kanbara, T. Saibara, T. Mori, S. Kawata, H. Uto, S. Takami, S. Sumida, T. Takamura, M. Kawanaka, T. Okanoue, Japan NASH Study Group, Ministry of Health Labour and Welfare of Japan, “Characteristics of Patients with Nonalcoholic Steatohepatitis Who Develop Hepatocellular Carcinoma,” Clinical of Gastroenterology and Hepatology, Vol. 9, No. 5, 2011, pp. 428-433. doi:10.1016/j.cgh.2011.01.023

[23]   J. Bruix and M. Sherman, “Management of Hepatocellular Carcinoma: An Update,” 2011.

[24]   A. Forner, M. Reig and J. Bruix, “Alpha-Fetoprotein for Hepatocellular Carcinoma Diagnosis: The Demise of a Brilliant Star,” Gastroenterology, Vol. 137, No. 1, 2009, pp. 26-29. doi:10.1053/j.gastro.2009.05.014

[25]   J. M. Llovet, “Updated Treatment Approach to Hepatocellular Carcinoma,” Journal of Gastroenterology, Vol. 40, No. 3, 2005, pp. 225-235. doi:10.1007/s00535-005-1566-3

[26]   J. A. Marrero and S. Pelletier, “Hepatocellular Carcinoma,” Clinical Liver Disease, Vol. 10, No. 2, 2006, pp. 339-351.

[27]   J. Bruix, M. Sherman, J. M. Llovet, M. Beaugrand, R. Leoncioni, A. K. Burroughs, E. Christensen, L. Pagliaro, M. Colombo, J. Rodes and EASL Panel of Experts on H Clinical Liver Disease, “Clinical Management of Hepatocellular Carcinoma. Conclusions of the Barcelona-2000 EASL Conference. European Association for the Study of the Liver,” Journal of Hepatology, Vol. 35, No. 3, 2001, pp. 421-430. doi:10.1016/S0168-8278(01)00130-1

[28]   A. Forner, M. E. Reig, C. R. de Lope and J. Bruix, “Current Strategy for Staging and Treatment: The BCLC Update and Future Prospects,” Seminars of Liver Disease, Vol. 30, No. 1, 2010, pp. 61-74. doi:10.1055/s-0030-1247133

[29]   V. Mazzaferro, E. Regalia, R. Dogi, S. Andreola, A. Pulvirenti, F. Bozzetti, F. Montalto, M. Ammantuna, A. Morabito and L. Gennari, “Liver Transplantation for the Treatment of Small Hepatocellular Carcinomas in Patients with cirrhosis,” New England Journal of Medicine, Vol. 334, 1996, pp. 693-369. doi:10.1056/NEJM199603143341104

[30]   Y. K. Cho, J. K. Kim, M. Y. Kim, H. Rhim and J. K. Han, “Systematic Review of Randomized Trials for Hepatocellular Carcinoma Treated with Percutaneous Ablation Therapies,” Hepatology, Vol. 49, No. 2, 2009, pp. 453-459. doi:10.1002/hep.22648

[31]   M. S. Chen, J. Q. Li, Y. Zheng, R. P. Guo, H. H. Liang, Y. Q. Zhang, X. J. Lin and W. Y. Lau, “A Prospective Randomized Trial Comparing Per-Cutaneous Local Ablative Therapy and Partial Hepatectomy for Small Hepatocellular Carcinoma,” Annals of Surgery, Vol. 243, No. 3, 2006, pp. 321-328. doi:10.1097/01.sla.0000201480.65519.b8

[32]   T. Livraghi, F. Meloni, M. Di Stasi, E. Rolle, L. Solbiati, C. Tinelli and S. Rossi, “Sustained Complete Response and Complications Rates after Radiofrequency Ablation of Very Early Hepatocellular Carcinoma in Cirrhosis: Is Resection Still the Treatment of Choice?” Hepatology, Vol. 47, No. 1, 2008, pp. 82-89. doi:10.1002/hep.21933

[33]   R. N. H. Pugh, I. M. Murray-Lyon, J. L. Dawson, M. C. Pietroni and R. Williams, “Transection of the Oesophagus for Bleeding Oesophagealvarices,” British Journal of Surgery, Vol. 60, 1973, pp. 648-652. doi:10.1002/bjs.1800600817

[34]   J. B. Sorensen, M. Klee, T. Palshof and H. H. Hansen, “Performance Status Assessment in Cancer Patients. An Inter-Observer Variability Study,” British Journal of Cancer, Vol. 67, No. 4, 1993, pp. 773-775.

[35]   F. J. Carrilho, L. Kikuchi, F. Branco, C. S. Goncalves and A. A. Mattos, “Clinical and Epidemiological Aspects of Hepatocellular Carcinoma in Brazil,” Clinics (Sao Paulo), Vol. 65, No. 12, 2010, pp. 1285-1290. doi:10.1590/S1807-59322010001200010

[36]   R. Alves, M. Harriz, H. Vanini, D. Alves, S. Soares, T. Montalveme, D. Vanni, L. Capellano, G. Oliveira, K. Duarte, J. Ribeiro, D. Terrabuio, M. Viana, R. Moutinho, E. Taddeu, B. Guz and P. Poletti, “Carcinoma Hepatocelular: Aspectos Epidemiológicos em 210 Casos,” Revista AMRIGS, Vol. 53, No. S3, 2009, p. S43.

[37]   A. S. P. Ferreira, A. J. Dominici, R. M. S. Garcia, M. E. C. Cordeiro, T. L. R. Pinho, R. S. Werniz, E. C. Santos, G. F. R. C. Santos, B. N. Tanaka, C. S. F. Carvalho and K. F. C. S. Leal, “Características Clínico-Epidemiológicas de Pacientes com Hepatocarcionoma em Servico de Referência do Estado do Maranhao,” Revista AMRIGS, Vol. 53, No. S3, 2009, p. S79.

[38]   A. S. Goncalves, F. E. Pereira and L. C. Gayotto, “Hepatocellular Carcinoma in Brazil: Report of a National Survey (Florianopolis, SC, 1995),” Revista do Instituto de Medicina Tropical de Sao Paulo, Vol. 39, No. 3, 1997, pp. 165-170. doi:10.1590/S0036-46651997000300008

[39]   E. Fassio, S. Díaz, C. Santa, M. E. Reig, Y. Martínez Artola and A. Alves de Mattos, “Etiology of Hepatocellular Carcinoma in Latin America: A Prospective, Multicenter, International Study,” Annals of Hepatology, Vol. 9, No. 1, 2010, pp. 63-69.

[40]   M. Varela, M. Reig, M. de la Mata, A. Matilla, J. Bustamante, S. Pascual, J. Turnes, C. Aracil, A. Del Val, J. M. Pascasio, M. Rodríguez and J. Bruix, “Treatment Approach of Hepatocellular Carcinoma in Spain. Analysis of 705 Patients from 62 Centers,” Medicina Clinica (Barcelona), Vol. 134, No. 13, 2010, pp. 569-576.

[41]   European Association for the Study of the Liver; European Organization for Research and Treatment of Cancer, “EASL-EORTC Clinical Practice Guidelines: Management of Hepatocellular Carcinoma,” Journal of Hepatology, Vol. 56, No. 4, 2012, pp. 908-943.

[42]   R. F. Silva, P. S. Fucuta, J. Vieira, A. Volpatto, M. F. Rocha and E. Cartapatti, “Carcinoma Hepatocelular no Oeste de Sao Paulo: Registros de um Hospital Escola,” Gastroenterologia Endoscopia Digestiva, Vol. 20, 2001, p. PO249.

[43]   H. B. El-Serag, “Hepatocellular Carcinoma,” New England Journal of Medicine, Vol. 365, No. 12, 2011, pp. 1118-1112. doi:10.1056/NEJMra1001683

[44]   M. Sherman, “Hepatocellular Carcinoma: Epidemiology, Surveillance, and Diagnosis,” Seminars Liver Disease, Vol. 30, No. 1, 2010, pp. 3-16. doi:10.1055/s-0030-1247128

[45]   A. M. Di Bisceglie, A. C. Lyra, M. Schwartz, R. K. Reddy, P. Martin, G. Gores, A. S. Lok, K. B. Hussain, R. Gish, D. H. Van Thiel, Z. Younossi, M. Tong, T. Hassanein, L. Balart, J. Fleckenstein, S. Flamm, A. Blei, A. S. Befeler and Liver Cancer Network, “Hepatitis C-Related Hepatocellular Carcinoma in the United States: Influence of Ethnic Status,” American Journal of Gastroenterology, Vol. 98, No. 9, 2003, pp. 2060-2063.

[46]   F. X. Bosch, J. Ribes, M. Diaz and R. Cleries, “Primary Liver Cancer: Worldwide Incidence and Trends,” Gastroenterology, Vol. 127, No. 5, 2004, pp. S5-S16. doi:10.1053/j.gastro.2004.09.011

[47]   R. Raphe, H. C. C. Felício, M. F. Rocha, W. J. Duca, P. C. Arroyo Jr., D. D’Santi Neto, R. C. da Silva and R. F. da Silva, “Histopathologic Characteristics of Incidental Hepatocellular Carcinoma after Liver Transplantation,” Transplantation Procedings, Vol. 42, No. 2, 2010, pp. 505-506. doi:10.1016/j.transproceed.2010.01.034

[48]   F. Trevisani, P. E. D’Intino, A. M. Morselli-Labate, G. Mazzella, E. Accogli, P. Caraceni, M. Domenicali, S. D. Notariis, E. Roda and M. Bernardi, “Serum Alpha-Fetoprotein for Diagnosis of Hepatocellular Carcinoma in Patients with Chronic Liver Disease: Influence of HBsAg and Anti-HCV Status,” Journal of Hepatology, Vol. 34, No. 4, 2001, pp. 570-575.

[49]   J. A. Marrero, Z. Feng, Y. Wang, M. H. Nguyen, A. S. L. R. Roberts, K. R. Reddy, D. Harnois, J. M. Llovet, D. Normolle, J. Dalhgren, D. Chia, A. S. Lok, P. D. Wagner, S. Srivastava and M. Schwartz, “Alpha-Fetoprotein, Des-Gamma Carboxyprothrombin, and Lectin-Bound Alpha-Fetoprotein in Early Hepatocellular Carcinoma,” Gastroenterology, Vol. 137, No. 1, 2007, pp. 110-118.

[50]   A. S. Lok, R. K. Sterling, M. E. Everhart, E. C. Wright, J. C. Hoefs, A. M. Di Bisceglie, T. R. Morgan, H. Y. Kim, W. M. Lee, H. L. Bonkovsky, J. L. Dienstag and HALT-C Trial Group, “Des-Gamma-Carboxyprothrombin and Alpha-Fetoprotein as Biomarkers for the Early Detection of Hepatocellular Carcinoma,” Gastroenterology, Vol. 138, No. 2, 2010, pp. 493-502. doi:10.1053/j.gastro. 2009.10.031