Updates in the management of hepatocellular carcinoma

Gastroenterology and Hepatology

Volumn 7, Issue 1, 2011, Pages 16-24

  Wong, Robert ^a   Frenette, Catherine ^b,c  

^a CALIFORNIA PACIFIC MEDICAL CENTER   (United States)

^b Hepatocellular Carcinoma Program   (United States)

^c Barry S Levin Department of Transplantation   (United States)

Author keywords

Cancer screening and surveillance; Chemoembolization; Liver cancer staging; Locoregional therapy; Radiofrequency ablation; Sorafenib; Yttrium 90

Indexed keywords

ALPHA FETOPROTEIN; BEVACIZUMAB; DOXORUBICIN; ERLOTINIB; LIVER ENZYME; POLYVINYL ALCOHOL; SORAFENIB; STARCH MICROSPHERE; VIRUS DNA; YTTRIUM 90;

BARCELONA CLINIC LIVER CANCER STAGING SYSTEM; BLOOD CLOT; CANCER DIAGNOSIS; CANCER EPIDEMIOLOGY; CANCER OF THE LIVER ITALIAN PROGRAM SCORE; CANCER RISK; CANCER SCREENING; CANCER STAGING; CANCER SURGERY; CANCER SURVIVAL; CHEMOEMBOLIZATION; COMPUTER ASSISTED TOMOGRAPHY; ECHOGRAPHY; ETHNICITY; FAMILY HISTORY; HEPATITIS B VIRUS; HUMAN; INVASIVE PROCEDURE; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LIVER TOXICITY; LIVER TRANSPLANTATION; MICROWAVE THERAPY; NUCLEAR MAGNETIC RESONANCE IMAGING; OKUDA CLASSIFICATION MODEL; PERCUTANEOUS ETHANOL INJECTION; PRACTICE GUIDELINE; RACE; RADIOFREQUENCY ABLATION; REVIEW; SYSTEMIC THERAPY; VIRUS CARRIER;

EID: 79951800609     PISSN: 15547914     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (106)

1. Bruix J, Sherman M. AASLD Practice Guideline. Management of hepatocellular carcinoma: an update. Hepatology. 2010;1-35. http://www.aasld. org/practiceguidelines/Documents/Bookmarked%20practice%20Guidelines/ Hccupdate2010.pdf.
2. El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology. 2008;134:1752-1763.
3. Shariff MI, Cox IJ, Gomaa AI, Khan SA, Gedroyc W, Taylor-Robinson SD. Hepatocellular carcinoma: current trends in worldwide epidemiology, risk factors, diagnosis and therapeutics. Expert Rev Gastroenterol Hepatol. 2009;3:353-367.
4. Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol. 2009;27:1485-1491.
5. Gish RG, Marrero JA, Benson AB. A multidisciplinary approach to the management of hepatocellular carcinoma. Gastroenterol Hepatol (N Y). 2010;6 (supp 7):1-14.
6. Schwartz M, Roayaie S, Konstadoulakis M. Strategies for the management of hepatocellular carcinoma. Nat Clin Pract Oncol. 2007;4:424-432.
7. Asmis T, Balaa F, Scully L, et al. Diagnosis and management of hepatocellular carcinoma: results of a consensus meeting of The Ottawa Hospital Cancer Centre. Curr Oncol. 2010;17:6-12.
8. Lopez PM, Villanueva A, Llovet JM. Systematic review: evidence-based management of hepatocellular carcinoma - an updated analysis of randomized controlled trials. Aliment Pharmacol Ther. 2006;23:1535-1547.
9. Beasley RP, Hwang LY, Lin CC, Chien CS. Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22,707 men in Taiwan. Lancet. 1981;2: 1129-1133.
10. Sakuma K, Saitoh N, Kasai M, et al. Relative risks of death due to liver disease among Japanese male adults having various statuses for hepatitis B s and e antigen/antibody in serum: a prospective study. Hepatology. 1988;8:1642-1646.
11. Hsu YS, Chien RN, Yeh CT, et al. Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B. Hepatology. 2002; 35:1522-1527.
12. Davila JA, Morgan RO, Richardson PA, Du XL, McGlynn KA, El-Serag HB. Use of surveillance for hepatocellular carcinoma among patients with cirrhosis in the United States. Hepatology. 2010;52:132-141.
13. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45:507-539.
14. Yang HI, Lu SN, Liaw YF, et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med. 2002;347:168-174.
15. Evans AA, Chen G, Ross EA, Shen FM, Lin WY, London WT. Eight-year follow-up of the 90,000-person Haimen City cohort: I. Hepatocellular carcinoma mortality, risk factors, and gender differences. Cancer Epidemiol Biomarkers Prev. 2002;11:369-376.
16. Huo TI, Wu JC, Lee PC, et al. Sero-clearance of hepatitis B surface antigen in chronic carriers does not necessarily imply a good prognosis. Hepatology. 1998;28:231-236.
17. Fattovich G, Giustina G, Realdi G, Corrocher R, Schalm SW. Long-term outcome of hepatitis B e antigen-positive patients with compensated cirrhosis treated with interferon alfa. European Concerted Action on Viral Hepatitis (EUROHEP). Hepatology. 1997;26:1338-1342.
18. Fattovich G, Giustina G, Sanchez-Tapias J, et al. Delayed clearance of serum HBsAg in compensated cirrhosis B: relation to interferon alpha therapy and disease prognosis. European Concerted Action on Viral Hepatitis (EUROHEP). Am J Gastroenterol. 1998;93:896-900.
19. Chen CJ, Yang HI, Su J, et al; REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65-73.
20. Manns MP, Czaja AJ, Gorham JD, et al. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010;51:2193-2223.
21. Trevisani F, D'Intino PE, Morselli-Labate AM, et al. Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status. J Hepatol. 2001;34:570-575.
22. Lok AS, Sterling RK, Everhart JE, et al; HALT-C Trial Group. Des-gamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma. Gastroenterology. 2010;138:493-502.
23. Shiraki K, Takase K, Tameda Y, Hamada M, Kosaka Y, Nakano T. A clinical study of lectin-reactive alpha-fetoprotein as an early indicator of hepatocellular carcinoma in the follow-up of cirrhotic patients. Hepatology. 1995;22:802-807.
24. Kumada T, Nakano S, Takeda I, et al. Clinical utility of Lens culinaris agglutinin-reactive alpha-fetoprotein in small hepatocellular carcinoma: special reference to imaging diagnosis. J Hepatol 1999;30:125-130.
25. Okuda K, Tanaka M, Kanazawa N, et al. Evaluation of curability and prediction of prognosis after surgical treatment for hepatocellular carcinoma by lens culinaris agglutinin-reactive alpha-fetoprotein. Int J Oncol. 1999;14:265-271.
26. Hayashi K, Kumada T, Nakano S, et al. Usefulness of measurement of Lens culinaris agglutininreactive fraction of alpha-fetoprotein as a marker of prognosis and recurrence of small hepatocellular carcinoma. Am J Gastroenterol. 1999;94:3028-3033.
27. Tamura Y, Igarashi M, Kawai H, Suda T, Satomura S, Aoyagi Y. Clinical advantage of highly sensitive on-chip immunoassay for fucosylated fraction of alpha-fetoprotein in patients with hepatocellular carcinoma. Dig Dis Sci. 2010;55: 3576-3583.
28. Sterling RK, Jeffers L, Gordon F, et al. Clinical utility of AFP-L3% measurement in North American patients with HCV-related cirrhosis. Am J Gastroenterol. 2007;102:2196-2205.
29. Volk ML, Hernandez JC, Su GL, Lok AS, Marrero JA. Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: a comparison of AFP, DCP, and AFP-L3. Cancer Biomark. 2007;3:79-87.
30. Marrero JA, Feng Z, Wang Y, et al. Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma. Gastroenterology. 2009;137:110-118.
31. Sato Y, Nakata K, Kato Y, et al. Early recognition of hepatocellular carcinoma based on altered profiles of alpha-fetoprotein. N Engl J Med. 1993;328:1802-1806.
32. Bolondi L, Sofia S, Siringo S, et al. Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis. Gut. 2001;48:251-259.
33. Christensen E, Schlichting P, Fauerholdt L, et al. Prognostic value of Child-Turcotte criteria in medically treated cirrhosis. Hepatology. 1984;4:430-435.
34. Wiesner R, Edwards E, Freeman R, et al. Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology. 2003;124:91-96.
35. Ravaioli M, Grazi GL, Ballardini G, et al. Liver transplantation with the MELD system: a prospective study from a single European center. Am J Transplant. 2006;6:1572-1577.
36. Freeman RB Jr, Edwards EB. Liver transplant waiting time does not correlate with waiting list mortality: implications for liver allocation policy. Liver Transpl. 2000;6:543-552.
37. Institute of Medicine. Analysis of waiting times. In: Organ Procurement and Transplantation: Assessing Current Policies and the Potential Impact of the DHHS Final Rule. Washington, DC: National Academy Press; 1999:57.
38. Organ Procurement and Transplantation Network - HRSA. Final rule with comment period. Fed Regist. 1998;63:16296.
39. Freeman RB Jr, Wiesner RH, Harper A, et al. The new liver allocation system: moving toward evidence-based transplantation policy. Liver Transpl. 2002;8: 851-858.
40. Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010:175.
41. Vauthey JN, Lauwers GY, Esnaola NF, et al. Simplified staging for hepatocellular carcinoma. J Clin Oncol. 2002;20:1527-1536.
42. Greene FL, Page DL, Fleming ID, et al, eds. AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer-Verlag; 2002.
43. Okuda K, Ohtsuki T, Obata H, et al. Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer. 1985;56:918-928.
44. The Cancer of the Liver Italian Program (CLIP) Investigators. Prospective validation of the CLIP score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma. Hepatology. 2000;31:840-845.
45. Grieco A, Pompili M, Caminiti G, et al. Prognostic factors for survival in patients with early-intermediate hepatocellular carcinoma undergoing non-surgical therapy: comparison of Okuda, CLIP, and BCLC staging systems in a single Italian centre. Gut. 2005;54:411-418.
46. Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19:329-338.
47. Cillo U, Vitale A, Grigoletto F, et al. Prospective validation of the Barcelona Clinic Liver Cancer staging system. J Hepatol. 2006;44:723-731.
48. Arii S, Yamaoka Y, Futagawa S, et al. Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas: a retrospective and nationwide survey in Japan. The Liver Cancer Study Group of Japan. Hepatology. 2000;32:1224-1229.
49. Takayama T, Makuuchi M, Hirohashi S, et al. Early hepatocellular carcinoma as an entity with a high rate of surgical cure. Hepatology. 1998;28:1241-1246.
50. Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology. 1999;30:1434-1440.
51. Fong Y, Sun RL, Jarnagin W, Blumgart LH. An analysis of 412 cases of hepatocellular carcinoma at a Western center. Ann Surg. 1999;229:790-800.
52. Grazi GL, Ercolani G, Pierangeli F, et al. Improved results of liver resection for hepatocellular carcinoma on cirrhosis give the procedure added value. Ann Surg. 2001;234:71-78.
53. Nathan H, Schulick RD, Choti MA, et al. Predictors of survival after resection of early hepatocellular carcinoma. Ann Surg. 2009;249:799-805.
54. Poon RT, Fan ST, Ng IO, Wong J. Significance of resection margin in hepatectomy for hepatocellular carcinoma: A critical reappraisal. Ann Surg. 2000;231:544-551.
55. Llovet JM, Schwartz M, Mazzaferro V. Resection and liver transplantation for hepatocellular carcinoma. Semin Liver Dis. 2005;25:181-200.
56. Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693-699.
57. Bismuth H, Majno PE, Adam R. Liver transplantation for hepatocellular carcinoma. Semin Liver Dis. 1999;19:311-322.
58. Bismuth H, Chiche L, Adam R, Castaing D. Surgical treatment of hepatocellular carcinoma in cirrhosis: liver resection or transplantation? Transplant Proc. 1993;25:1066-1067.
59. Llovet JM, Bruix J, Fuster J, et al. Liver transplantation for small hepatocellular carcinoma: the tumor-node-metastasis classification does not have prognostic power. Hepatology. 1998;27:1572-1577.
60. Jonas S, Bechstein WO, Steinmuller T, et al. Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis. Hepatology. 2001;33:1080-1086.
61. Pomfret E, Washburn K, Wald C, et al. Report of a national conference on liver allocation in patients with hepatocellular carcinoma in the United States. Liver Transpl. 2010;16:262-278.
62. Mazzaferro V, Llovet JM, Miceli R, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10:35-43.
63. Toso C, Trotter J, Wei A, et al. Total tumor volume predicts risk of recurrence following liver transplantation in patients with hepatocellular carcinoma. Liver Transpl. 2008;14:1107-1115.
64. Yao FY, Xiao L, Bass NM, Kerlan R, Ascher NL, Roberts JP. Liver transplantation for hepatocellular carcinoma: validation of the UCSF-expanded criteria based on preoperative imaging. Am J Transplant. 2007;7:2587-2596.
65. Yao FY, Ferrell L, Bass NM, Bacchetti P, Ascher NL, Roberts JP. Liver transplantation for hepatocellular carcinoma: comparison of the proposed UCSF criteria with the Milan criteria and the Pittsburgh modified TNM criteria. Liver Transpl. 2002;8:765-774.
66. Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33:1394-1403.
67. Yao FY, Xiao L, Bass NM, Kerlan R, Ascher NL, Roberts JP. Liver transplantation for hepatocellular carcinoma: validation of the UCSF expanded criteria based on pre-operative imaging. Am J Transpl. 2007;7:2587-2596.
68. Yao FY. Expanding criteria for hepatocellular carcinoma: down-staging with a view to liver transplantation - yes. Semin Liv Dis. 2006;26:239-247.
69. Yao FY, Hirose R, LaBerge J, et al. A prospective study on down-staging of hepatocellular carcinoma prior to liver transplantation. Liver Transpl. 2005; 11:1505-1514.
70. Yao FY, Kerlan RK Jr, Hirose R, et al. Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis. Hepatology. 2008;48:819-827.
71. Lencioni R. Loco-regional treatment of hepatocellular carcinoma. Hepatology. 2010;52:762-773.
72. Okada S. Local ablation therapy for hepatocellular carcinoma. Semin Liver Dis. 1999;19:323-328.
73. Ishii H, Okada S, Nose H, et al. Local recurrence of hepatocellular carcinoma after percutaneous ethanol injection. Cancer. 1996;77:1792-1796.
74. Lencioni RA, Allgaier HP, Cioni D, et al. Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection. Radiology. 2003;228:235-240.
75. Livraghi T, Goldberg SN, Lazzaroni S, Meloni F, Solbiati L, Gazelle GS. Small hepatocellular carcinoma: treatment with radio-frequency ablation versus ethanol injection. Radiology. 1999;210:655-661.
76. Cho YK, Kim JK, Kim MY, Rhim H, Han JK. Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies. Hepatology. 2009;49:453-459.
77. Lin SM, Lin CJ, Lin CC, Hsu CW, Chen YC. Radiofrequency ablation improves prognosis compared with ethanol injection for hepatocellular carcinoma < or =4 cm. Gastroenterology. 2004;127:1714-1723.
78. Shiina S, Teratani T, Obi S, et al. A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma. Gastroenterology. 2005;129:122-130.
79. Chen MS, Li JQ, Zheng Y, et al. A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg. 2006;243:321-328.
80. Shibata T, Iimuro Y, Yamamoto Y, et al. Small hepatocellular carcinoma: comparison of radio-frequency ablation and percutaneous microwave coagulation therapy. Radiology. 2002;223:331-337.
81. Yu NC, Lu DS, Raman SS, et al. Hepatocellular carcinoma: microwave ablation with multiple straight and loop antenna clusters - pilot comparison with pathologic findings. Radiology. 2006;239:269-275.
82. Martin RC, Scoggins CR, McMasters KM. Safety and efficacy of microwave ablation of hepatic tumors: a prospective review of a 5-year experience. Ann Surg Oncol. 2010;17:171-178.
83. Llovet JM, Real MI, Montaña X, et al; Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359:1734-1739.
84. Cammà C, Schepis F, Orlando A, et al. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology. 2002;224:47-54.
85. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003; 37:429-442.
86. Lewandowski RJ, Kulik LM, Riaz A, et al. A comparative analysis of transarterial downstaging for hepatocellular carcinoma: chemoembolization versus radioembolization. Am J Transplant. 2009;9:1920-1928.
87. Chuang VP, Wallace S, Soo CS, Charnsangavej C, Bowers T. Therapeutic Ivalon embolization of hepatic tumors. AJR Am J Roentgenol. 1982;138:289-294.
88. Carr BI, Zajko A, Bron K, Orons P, Sammon J, Baron R. Phase II study of Spherex (degradable starch microspheres) injected into the hepatic artery in conjunction with doxorubicin and cisplatin in the treatment of advanced-stage hepatocellular carcinoma: interim analysis. Semin Oncol. 1997;24(suppl 6):97-99.
89. Bruix J, Castells A, Montanya X, et al. Phase II study of transarterial embolization in European patients with hepatocellular carcinoma: need for controlled trials. Hepatology. 1994;20:643-650.
90. Gunji T, Kawauchi N, Ohnishi S, et al. Treatment of hepatocellular carcinoma associated with advanced cirrhosis by transcatheter arterial chemoembolization using autologous blood clot: a preliminary report. Hepatology. 1992;15:252-257.
91. Lammer J, Malagari K, Vogl T, et al; PRECISION V Investigators. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol. 2010;33:41-52.
92. Dhanasekaran R, Kooby DA, Staley CA, Kauh JS, Khanna V, Kim HS. Comparison of conventional transarterial chemoembolization (TACE) and chemoembolization with doxorubicin drug eluting beads (DEB) for unresectable hepatocelluar carcinoma (HCC). J Surg Oncol. 2010;101:476-480.
93. Nicolini A, Martinetti L, Crespi S, Maggioni M, Sangiovanni A. Transarterial chemoembolization with epirubicin-eluting beads versus transarterial embolization before liver transplantation for hepatocellular carcinoma. J Vasc Interv Radiol. 2010;21:327-332.
94. Geschwind JF, Salem R, Carr BI, et al. Yttrium-90 microspheres for the treatment of hepatocellular carcinoma. Gastroenterology. 2004;127:S194-S205.
95. Salem R, Lewandowski RJ, Atassi B, et al. Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival. J Vasc Interv Radiol. 2005;16:1627-1639.
96. Sangro B, Bilbao JI, Boan J, et al. Radioembolization using 90Y-resin microspheres for patients with advanced hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2006;66:792-800.
97. Kooby DA, Egnatashvili V, Srinivasan S, et al. Comparison of yttrium-90 radioembolization and transcatheter arterial chemoembolization for the treatment of unresectable hepatocellular carcinoma. J Vasc Interv Radiol. 2010;21:224-230.
98. Kulik LM, Carr BI, Mulcahy MF, et al. Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis. Hepatology. 2008;47:71-81.
99. Salem R, Lewandowski RJ, Mulcahy MF, et al. Radioembolization for hepatocellular carcinoma using yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology. 2010;138:52-64.
100. Yeo W, Mok TS, Zee B, et al. A randomized phase III study of doxorubicin versus cisplatin/interferon alpha-2b/doxorubicin/fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma. J Natl Cancer Inst. 2005;97:1532-1538.
101. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378-390.
102. 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.
103. Siegel AB, Cohen EI, Ocean A, et al. Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma. J Clin Oncol. 2008;26:2992-2298.
104. Pore N, Jiang Z, Gupta A, Cerniglia G, Kao GD, Maity A. EGFR tyrosine kinase inhibitors decrease VEGF expression by both hypoxia-inducible factor (HIF)-1-independent and HIF-1-dependent mechanisms. Cancer Res. 2006;66:3197-3204.
105. Philip PA, Mahoney MR, Allmer C, et al. Phase II study of Erlotinib (OSI-774) in patients with advanced hepatocellular cancer. J Clin Oncol. 2005;23:6657-6663.
106. Yau T, Chan P, Epstein R, Poon RT. Management of advanced hepatocellular carcinoma in the era of targeted therapy. Liver Int. 2009;29:1-7.