Evidence-Based Diagnosis, Staging, and Treatment of Patients with Hepatocellular Carcinoma

Gastroenterology

Volumn 150, Issue 4, 2016, Pages 835-853

  Bruix, Jordi ^a   Reig, Maria ^a   Sherman, Morris ^b  

^a UNIVERSITY OF BARCELONA   (Spain)

^b TORONTO GENERAL HOSPITAL   (Canada)

Author keywords

BCLC; Early Detection; Liver Cancer; Therapy

Indexed keywords

MOLECULAR MARKER;

ARTICLE; CANCER DIAGNOSIS; CANCER EPIDEMIOLOGY; CANCER PATIENT; CANCER PROGNOSIS; CANCER RADIOTHERAPY; CANCER STAGING; CANCER SURVIVAL; CANCER THERAPY; CHEMOEMBOLIZATION; ECHOGRAPHY; EVIDENCE BASED PRACTICE; HUMAN; LIVER CELL CARCINOMA; PRIORITY JOURNAL; SURVIVAL TIME; TUMOR BIOPSY; TUMOR VOLUME; ALGORITHM; CARCINOMA, HEPATOCELLULAR; DISEASE COURSE; EVIDENCE BASED MEDICINE; LIVER NEOPLASMS; MORTALITY; PATHOLOGY; PATIENT SELECTION; PREDICTIVE VALUE; RISK FACTOR; TIME FACTOR; TREATMENT OUTCOME;

ALGORITHMS; CARCINOMA, HEPATOCELLULAR; DISEASE PROGRESSION; EVIDENCE-BASED MEDICINE; HUMANS; LIVER NEOPLASMS; NEOPLASM STAGING; PATIENT SELECTION; PREDICTIVE VALUE OF TESTS; RISK FACTORS; TIME FACTORS; TREATMENT OUTCOME;

EID: 84962793735     PISSN: 00165085     EISSN: 15280012     Source Type: Journal    
DOI: 10.1053/j.gastro.2015.12.041     Document Type: Review

References (204)

1. J. Ferlay, I.I. Soerjomataram, R. Dikshit, and et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012 Int J Cancer 136 2014 E359 E386
2. H.B. El-Serag, J.A. Davila, N.J. Petersen, and et al. The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update Ann Intern Med 139 2003 817 823
3. J. Bridgewater, P.R. Galle, S.A. Khan, and et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma J Hepatol 60 2014 1268 1289
4. J.N. Honeyman, E.P. Simon, N. Robine, and et al. Detection of a recurrent DNAJB1-PRKACA chimeric transcript in fibrolamellar hepatocellular carcinoma Science 343 2014 1010 1014
5. J.C. Sheu, J.L. Sung, D.S. Chen, and et al. Growth rate of asymptomatic hepatocellular carcinoma and its clinical implications Gastroenterology 89 1985 259 266
6. L. Barbara, G. Benzi, S. Gaiani, and et al. Natural history of small untreated hepatocellular carcinoma in cirrhosis: a multivariate analysis of prognostic factors of tumor growth rate and patient survival Hepatology 16 1992 132 137
7. B. Taouli, J.S.K. Goh, Y. Lu, and et al. Growth rate of hepatocellular carcinoma: evaluation with serial computed tomography or magnetic resonance imaging J Comput Assist Tomogr 29 2005 425 429
8. A. Furlan, D. Marin, F. Agnello, and et al. Hepatocellular carcinoma presenting at contrast-enhanced multi-detector-row computed tomography or gadolinium-enhanced magnetic resonance imaging as a small (≤2 cm), indeterminate nodule: growth rate and optimal interval time for imaging follow-up J Comput Assist Tomogr 36 2012 20 25
9. J. Bruix, and M. Sherman Management of hepatocellular carcinoma: an update Hepatology 53 2011 1020 1022
10. J. Bruix, and M. Sherman Management of hepatocellular carcinoma Hepatology 42 2005 1020 1022
11. M.-F. Yuen, Y. Tanaka, D.Y.-T. Fong, and et al. Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B J Hepatol 50 2009 80 88
12. V.W.-S. Wong, S.L. Chan, F. Mo, and et al. Clinical scoring system to predict hepatocellular carcinoma in chronic hepatitis B carriers J Clin Oncol 28 2010 1660 1665
13. G.L.-H. Wong, H.L.-Y. Chan, C.K.-Y. Wong, and et al. Liver stiffness-based optimization of hepatocellular carcinoma risk score in patients with chronic hepatitis B J Hepatol 60 2014 339 345
14. H.-I. Yang, M.-F. Yuen, H.L.-Y. Chan, and et al. Risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B): development and validation of a predictive score Lancet Oncol 12 2011 568 574
15. M.-H. Lee, H.-I. Yang, J. Liu, and et al. Prediction models of long-term cirrhosis and hepatocellular carcinoma risk in chronic hepatitis B patients: risk scores integrating host and virus profiles Hepatology 58 2013 546 554
16. A.S. Lok, L.B. Seeff, T.R. Morgan, and et al. Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease Gastroenterology 136 2009 138 148
17. H.B. El-Serag, F. Kanwal, J.A. Davila, and et al. A new laboratory-based algorithm to predict development of hepatocellular carcinoma in patients with hepatitis C and cirrhosis Gastroenterology 146 2014 1249 1255.e1
18. J.A. Flemming, J.D. Yang, E. Vittinghoff, and et al. Risk prediction of hepatocellular carcinoma in patients with cirrhosis: the ADRESS-HCC risk model Cancer 120 2014 3485 3493
19. Y.-C. Hung, C.-L. Lin, C.-J. Liu, and et al. Development of risk scoring system for stratifying population for hepatocellular carcinoma screening Hepatology 61 2015 1934 1944
20. T. Michikawa, M. Inoue, N. Sawada, and et al. Development of a prediction model for 10-year risk of hepatocellular carcinoma in middle-aged Japanese: the Japan Public Health Center-based Prospective Study Cohort II Prev Med 55 2012 137 143
21. K.-C. Chang, Y.-Y. Wu, C.-H. Hung, and et al. Clinical-guide risk prediction of hepatocellular carcinoma development in chronic hepatitis C patients after interferon-based therapy Br J Cancer 109 2013 2481 2488
22. K.S. Jung, S.U. Kim, S.H. Ahn, and et al. Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using liver stiffness measurement (FibroScan) Hepatology 53 2011 885 894
23. R. Masuzaki, R. Tateishi, H. Yoshida, and et al. Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography Hepatology 49 2009 1954 1961
24. S.H. Shin, S.U. Kim, J.Y. Park, and et al. Liver stiffness-based model for prediction of hepatocellular carcinoma in chronic hepatitis B virus infection: comparison with histological fibrosis Liver Int 35 2015 1054 1062
25. F.A. Lederle, and C. Pocha Screening for liver cancer: the rush to judgment Ann Intern Med 156 2012 387 389
26. J.-G. Chen, D.M. Parkin, Q.-G. Chen, and et al. Screening for liver cancer: results of a randomised controlled trial in Qidong, China J Med Screen 10 2003 204 209
27. B.H. Zhang, B.H. Yang, and Z.Y. Tang Randomized controlled trial of screening for hepatocellular carcinoma J Cancer Res Clin Oncol 130 2004 417 422
28. Y.-P. Yeh, T.-H. Hu, P.-Y. Cho, and et al. Evaluation of abdominal ultrasonography mass screening for hepatocellular carcinoma in Taiwan Hepatology 59 2014 1840 1849
29. F.P. Sarasin, E. Giostra, and A. Hadengue Cost-effectiveness of screening for detection of small hepatocellular carcinoma in western patients with Child-Pugh class A cirrhosis Am J Med 101 1996 422 434
30. M.R. Arguedas, V.K. Chen, M.A. Eloubeidi, and et al. Screening for hepatocellular carcinoma in patients with hepatitis C cirrhosis: a cost-utility analysis Am J Gastroenterol 98 2003 679 690
31. S. Saab, D. Ly, J. Nieto, and et al. Hepatocellular carcinoma screening in patients waiting for liver transplantation: a decision analytic model Liver Transpl 9 2003 672 681
32. S.M. Lin, C.J. Lin, C.C. Lin, and et al. Randomised controlled trial comparing percutaneous radiofrequency thermal ablation, percutaneous ethanol injection, and percutaneous acetic acid injection to treat hepatocellular carcinoma of 3 cm or less Gut 54 2005 1151 1156
33. D. Patel, N.A. Terrault, F.Y. Yao, and et al. Cost-effectiveness of hepatocellular carcinoma surveillance in patients with hepatitis C virus-related cirrhosis Clin Gastroenterol Hepatol 3 2005 75 84
34. K. Nouso, H. Tanaka, S. Uematsu, and et al. Cost-effectiveness of the surveillance program of hepatocellular carcinoma depends on the medical circumstances J Gastroenterol Hepatol 23 2008 437 444
35. J. Thompson Coon, G. Rogers, P. Hewson, and et al. Surveillance of cirrhosis for hepatocellular carcinoma: a cost-utility analysis Br J Cancer 98 2008 1166 1175
36. K.L. Andersson, J.A. Salomon, S.J. Goldie, and et al. Cost effectiveness of alternative surveillance strategies for hepatocellular carcinoma in patients with cirrhosis Clin Gastroenterol Hepatol 6 2008 1418 1424
37. F. Izzo, M. Piccirillo, V. Albino, and et al. Prospective screening increases the detection of potentially curable hepatocellular carcinoma: results in 8,900 high-risk patients HPB (Oxford) 15 2013 985 990
38. E. Ando, R. Kuromatsu, M. Tanaka, and et al. Surveillance program for early detection of hepatocellular carcinoma in Japan: results of specialized department of liver disease J Clin Gastroenterol 40 2006 942 948
39. S.-N. Lu, J.-H. Wang, P.-F. Chen, and et al. Community-based mass ultrasonographic screening of hepatocellular carcinoma among thrombocytopenic adults Cancer Epidemiol Biomarkers Prev 17 2008 1813 1821
40. A. Cucchetti, F. Trevisani, A. Pecorelli, and et al. Estimation of lead-time bias and its impact on the outcome of surveillance for the early diagnosis of hepatocellular carcinoma J Hepatol 61 2014 333 341
41. A. Singal, M.L. Volk, A. Waljee, and et al. Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis Aliment Pharmacol Ther 30 2009 37 47
42. D. Kansagara, J. Papak, A.S. Pasha, and et al. Screening for hepatocellular carcinoma in chronic liver disease: a systematic review Ann. Intern. Med 161 2014 261 269
43. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma J Hepatol 56 2012 908 943
44. Y. Asaoka, R. Tateishi, R. Nakagomi, and et al. Frequency of and predictive factors for vascular invasion after radiofrequency ablation for hepatocellular carcinoma PLoS One 9 2014 e111662
45. S.H. Kang, D.Y. Kim, S.M. Jeon, and et al. Clinical characteristics and prognosis of hepatocellular carcinoma with different sets of serum AFP and PIVKA-II levels Eur J Gastroenterol Hepatol 24 2012 849 856
46. Y.E. Chon, G.H. Choi, M.H. Lee, and et al. Combined measurement of preoperative α-fetoprotein and des-γ-carboxy prothrombin predicts recurrence after curative resection in patients with hepatitis-B-related hepatocellular carcinoma Int J Cancer 131 2012 2332 2341
47. F. Trevisani, P.E. D'Intino, A.M. Morselli-Labate, and 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 34 2001 570 575
48. D. Pateron, N. Ganne, J.C. Trinchet, and et al. Prospective study of screening for hepatocellular carcinoma in Caucasian patients with cirrhosis J Hepatol 20 1994 65 71
49. M. Sherman, K.M. Peltekian, and C. Lee Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population Hepatology 22 1995 432 438
50. A.S. Lok, R.K. Sterling, J.E. Everhart, and et al. Des-gamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma Gastroenterology 138 2010 493 502
51. M. Zoli, D. Magalotti, G. Bianchi, and et al. Efficacy of a surveillance program for early detection of hepatocellular carcinoma Cancer 78 1996 977 985
52. L. Bolondi, S. Sofia, S. Siringo, and et al. Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis Gut 48 2001 251 259
53. M.J. Tong, L.M. Blatt, and V.W. Kao Surveillance for hepatocellular carcinoma in patients with chronic viral hepatitis in the United States of America J Gastroenterol Hepatol 16 2001 553 559
54. J.A. Marrero, Z. Feng, Y. Wang, and et al. Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma Gastroenterology 137 2009 110 118
55. J. Rimola, A. Forner, M. Reig, and et al. Cholangiocarcinoma in cirrhosis: absence of contrast washout in delayed phases by magnetic resonance imaging avoids misdiagnosis of hepatocellular carcinoma Hepatology 50 2009 791 798
56. M. Biselli, F. Conti, A. Gramenzi, and et al. A new approach to the use of α-fetoprotein as surveillance test for hepatocellular carcinoma in patients with cirrhosis Br J Cancer 112 2015 69 76
57. H. Oka, A. Saito, K. Ito, and et al. Multicenter prospective analysis of newly diagnosed hepatocellular carcinoma with respect to the percentage of Lens culinaris agglutinin-reactive alpha-fetoprotein J Gastroenterol Hepatol 16 2001 1378 1383
58. R.K. Sterling, L. Jeffers, F. Gordon, and et al. Utility of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein and des-gamma-carboxy prothrombin, alone or in combination, as biomarkers for hepatocellular carcinoma Clin Gastroenterol Hepatol 7 2009 104 113
59. A.G. Singal, H.S. Conjeevaram, M.L. Volk, and et al. Effectiveness of hepatocellular carcinoma surveillance in patients with cirrhosis Cancer Epidemiol Biomarkers Prev 21 2012 793 799
60. C. Pocha, E. Dieperink, K.A. McMaken, and et al. Surveillance for hepatocellular cancer with ultrasonography vs. computed tomography - a randomised study Aliment Pharmacol Ther 38 2013 303 312
61. J.-C. Trinchet, C. Chaffaut, V. Bourcier, and et al. Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: a randomized trial comparing 3- and 6-month periodicities Hepatology 54 2011 1987 1997
62. J.-H. Wang, K.-C. Chang, K.-M. Kee, and et al. Hepatocellular carcinoma surveillance at 4- vs. 12-month intervals for patients with chronic viral hepatitis: a randomized study in community Am J Gastroenterol 108 2013 416 424
63. K.-H. Han, D.Y. Kim, J.Y. Park, and et al. Survival of hepatocellular carcinoma patients may be improved in surveillance interval not more than 6 months compared with more than 6 months: a 15-year prospective study J Clin Gastroenterol 47 2013 538 544
64. A. Forner, R. Vilana, C. Ayuso, and et al. Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma Hepatology 47 2008 97 104
65. A. Sangiovanni, M.A. Manini, M. Iavarone, and et al. The diagnostic and economic impact of contrast imaging techniques in the diagnosis of small hepatocellular carcinoma in cirrhosis Gut 59 2010 638 644
66. K. Khalili, T.K. Kim, H.-J. Jang, and et al. Optimization of imaging diagnosis of 1-2 cm hepatocellular carcinoma: an analysis of diagnostic performance and resource utilization J Hepatol 54 2011 723 728
67. D.G. Mitchell, J. Bruix, M. Sherman, and et al. LI-RADS (Liver Imaging Reporting and Data System): Summary, discussion, consensus of the LI-RADS Management Working Group and future directions Hepatology 61 2015 1056 1065
68. A. Darnell, A. Forner, J. Rimola, and et al. Liver imaging reporting and data system with MR imaging: evaluation in nodules 20 mm or smaller detected in cirrhosis at screening US Radiology 275 2015 698 707
69. M1 Galassi, M. Iavarone, S. Rossi, and et al. Patterns of appearance and risk of misdiagnosis of intrahepatic cholangiocarcinoma in cirrhosis at contrast enhanced ultrasound Liver Int 33 2013 771 779
70. R. Vilana, A. Forner, L. Bianchi, and et al. Intrahepatic peripheral cholangiocarcinoma in cirrhosis patients may display a vascular pattern similar to hepatocellular carcinoma on contrast-enhanced ultrasound Hepatology 51 2010 2020 2029
71. Pathologic diagnosis of early hepatocellular carcinoma: a report of the International Consensus Group for Hepatocellular Neoplasia Hepatology 49 2009 658 664
72. L. Di Tommaso, A. Destro, J.Y. Seok, and et al. The application of markers (HSP70 GPC3 and GS) in liver biopsies is useful for detection of hepatocellular carcinoma J Hepatol 50 2009 746 754
73. L. Di Tommaso, A. Destro, V. Fabbris, and et al. Diagnostic accuracy of clathrin heavy chain staining in a marker panel for the diagnosis of small hepatocellular carcinoma Hepatology 53 2011 1549 1557
74. S. Tremosini, A. Forner, L. Boix, and 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 61 2012 1481 1487
75. J.M. Llovet, Y. Chen, E. Wurmbach, and et al. A molecular signature to discriminate dysplastic nodules from early hepatocellular carcinoma in HCV cirrhosis Gastroenterology 131 2006 1758 1767
76. M. Torbenson, and P. Schirmacher Liver cancer biopsy - back to the future? Hepatology 61 2015 431 433
77. M. Sherman, and J. Bruix Biopsy for liver cancer: how to balance research needs with evidence-based clinical practice Hepatology 61 2015 433 436
78. H.G. Welch, and W.C. Black Overdiagnosis in cancer J Natl Cancer Inst 102 2010 605 613
79. J.M. Llovet, C. Bru, and J. Bruix Prognosis of hepatocellular carcinoma: the BCLC staging classification Semin Liver Dis 19 1999 329 338
80. J.M. Llovet, A. Burroughs, and J. Bruix Hepatocellular carcinoma Lancet 362 2003 1907 1917
81. A. Forner, J.M. Llovet, and J. Bruix Hepatocellular carcinoma Lancet 379 2012 1245 1255
82. M. Reig, A. Darnell, A. Forner, and et al. Systemic therapy for hepatocellular carcinoma: the issue of treatment stage migration and registration of progression using the BCLC-refined RECIST Semin Liver Dis 34 2014 444 455
83. A. Forner, M. Gilabert, J. Bruix, and et al. Treatment of intermediate-stage hepatocellular carcinoma Nat Rev Clin Oncol 11 2014 525 535
84. C.R. de Lope, S. Tremosini, A. Forner, and et al. Management of HCC J Hepatol 56 suppl 1 2012 S75 S87
85. R.N. Pugh, I.M. Murray-Lyon, J.L. Dawson, and et al. Transection of the oesophagus for bleeding oesophageal varices Br J Surg 60 1973 646 649
86. G. D'Amico, G. Garcia-Tsao, and L. Pagliaro Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies J Hepatol 44 2006 217 231
87. E.A. Tsochatzis, J. Bosch, and A.K. Burroughs Liver cirrhosis Lancet 383 2014 1749 1761
88. J.M. Llovet, S. Ricci, V. Mazzaferro, and et al. Sorafenib in advanced hepatocellular carcinoma N Engl J Med 359 2008 378 390
89. M. Malinchoc, P.S. Kamath, F.D. Gordon, and et al. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts Hepatology 31 2000 864 871
90. G. Cabibbo, M. Enea, M. Attanasio, and et al. A meta-analysis of survival rates of untreated patients in randomized clinical trials of hepatocellular carcinoma Hepatology 51 2010 1274 1283
91. P.J. Johnson, S. Berhane, C. Kagebayashi, and et al. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade J Clin Oncol 33 2015 550 558
92. J.M. Llovet, A.M. Di Bisceglie, J. Bruix, and et al. Design and endpoints of clinical trials in hepatocellular carcinoma J Natl Cancer Inst 100 2008 698 711
93. C. Ripoll, R.J. Groszmann, G. Garcia-Tsao, and et al. Hepatic venous pressure gradient predicts development of hepatocellular carcinoma independently of severity of cirrhosis J Hepatol 50 2009 923 928
94. A. Berzigotti, M. Reig, J.G. Abraldes, and et al. Portal hypertension and the outcome of surgery for hepatocellular carcinoma in compensated cirrhosis: a systematic review and meta-analysis Hepatology 61 2015 526 536
95. Y. Hoshida, A. Villanueva, M. Kobayashi, and et al. Gene expression in fixed tissues and outcome in hepatocellular carcinoma N Engl J Med 359 2008 1995 2004
96. J.C. Nault, A. de Reynies, A. Villanueva, and et al. A hepatocellular carcinoma 5-gene score associated with survival of patients after liver resection Gastroenterology 145 2013 176 187
97. D.Y. Zhang, N. Goossens, J. Guo, and et al. A hepatic stellate cell gene expression signature associated with outcomes in hepatitis C cirrhosis and hepatocellular carcinoma after curative resection Gut 2015 Jun 4 [Epub ahead of print]
98. J. Zucman-Rossi, A. Villanueva, J.-C. Nault, and et al. The genetic landscape and biomarkers of hepatocellular carcinoma Gastroenterology 149 2015 1226 1239
99. E.J. Fox, and L.A. Loeb Cancer: one cell at a time Nature 512 2014 143 144
100. R. Pinyol, J.C. Nault, I.M. Quetglas, and et al. Molecular profiling of liver tumors: classification and clinical translation for decision making Semin Liver Dis 34 2014 363 375
101. F. Borel, P. Konstantinova, and P.L.M. Jansen Diagnostic and therapeutic potential of miRNA signatures in patients with hepatocellular carcinoma J Hepatol 56 2012 1371 1383
102. R. Romagnoli, V. Mazzaferro, and J. Bruix Surgical resection for hepatocellular carcinoma: moving from what can be done to what is worth doing Hepatology 62 2015 340 342
103. N.F. Esnaola, G.Y. Lauwers, N.Q. Mirza, and et al. Predictors of microvascular invasion in patients with hepatocellular carcinoma who are candidates for orthotopic liver transplantation J Gastrointest Surg 6 2002 224 232
104. C. Wald, M.W. Russo, J.K. Heimbach, and et al. New OPTN/UNOS policy for liver transplant allocation: standardization of liver imaging, diagnosis, classification, and reporting of hepatocellular carcinoma Radiology 266 2013 376 382
105. T. Livraghi, F. Meloni, M. Di Stasi, and et al. Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: Is resection still the treatment of choice? Hepatology 47 2008 82 89
106. S. Roayaie, K. Obeidat, C. Sposito, and et al. Resection of hepatocellular cancer ≤2 cm: results from two Western centers Hepatology 57 2013 1426 1435
107. P.E. Majno, G. Mentha, and V. Mazzaferro Partial hepatectomy versus radiofrequency ablation for hepatocellular carcinoma: confirming the trial that will never be, and some comments on the indications for liver resection Hepatology 51 2010 1116 1118
108. Y.K. Cho, J.K. Kim, W.T. Kim, and et al. Hepatic resection versus radiofrequency ablation for very early stage hepatocellular carcinoma: a Markov model analysis Hepatology 51 2010 1284 1290
109. A. Cucchetti, F. Piscaglia, M. Cescon, and et al. Cost-effectiveness of hepatic resection versus percutaneous radiofrequency ablation for early hepatocellular carcinoma J Hepatol 59 2013 300 307
110. J.P. Roberts, A. Venook, R. Kerlan, and et al. Hepatocellular carcinoma: Ablate and wait versus rapid transplantation Liver Transpl 16 2010 925 929
111. J. Ferrer-Fàbrega, A. Forner, A. Liccioni, and et al. Prospective validation of "ab initio" liver transplantation in hepatocellular carcinoma upon detection of risk factors for recurrence after resection Hepatology 63 2016 839 849
112. J. Bruix, G.J. Gores, and V. Mazzaferro Hepatocellular carcinoma: clinical frontiers and perspectives Gut 63 2014 844 855
113. J. Bruix, A. Castells, J. Bosch, and et al. Surgical resection of hepatocellular carcinoma in cirrhotic patients: prognostic value of preoperative portal pressure Gastroenterology 111 1996 1018 1022
114. J.M. Llovet, J. Fuster, and J. Bruix Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation Hepatology 30 1999 1434 1440
115. T. Ishizawa, K. Hasegawa, T. Aoki, and et al. Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma Gastroenterology 134 2008 1908 1916
116. V. Mazzaferro, S. Bhoori, C. Sposito, and et al. Milan criteria in liver transplantation for hepatocellular carcinoma: an evidence-based analysis of 15 years of experience Liver Transpl 17 suppl 2 2011 S44 S57
117. V. Mazzaferro, E. Regalia, R. Doci, and et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis N Engl J Med 334 1996 693 699
118. K.R. Prasad, R.S. Young, P. Burra, and et al. Summary of candidate selection and expanded criteria for liver transplantation for hepatocellular carcinoma: a review and consensus statement Liver Transpl 17 suppl 2 2011 S81 S89
119. V. Mazzaferro, J.M. Llovet, R. Miceli, and et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis Lancet Oncol 10 2009 35 43
120. A. Raj, J. McCall, and E. Gane Validation of the "Metroticket" predictor in a cohort of patients transplanted for predominantly HBV-related hepatocellular carcinoma J Hepatol 55 2011 1063 1068
121. C. Duvoux, F. Roudot-Thoraval, T. Decaens, and et al. Liver transplantation for hepatocellular carcinoma: a model including alpha-fetoprotein improves the performance of Milan criteria Gastroenterology 143 2012 985 986
122. C. Toso, S. Asthana, D.L. Bigam, and et al. Reassessing selection criteria prior to liver transplantation for hepatocellular carcinoma utilizing the Scientific Registry of Transplant Recipients database Hepatology 49 2009 832 838
123. E. Vibert, D. Azoulay, E. Hoti, and et al. Progression of alphafetoprotein before liver transplantation for hepatocellular carcinoma in cirrhotic patients: a critical factor Am J Transpl 10 2010 129 137
124. C. Duvoux, F. Roudot-Thoraval, T. Decaens, and et al. Liver transplantation for hepatocellular carcinoma: a model including α-fetoprotein improves the performance of Milan criteria Gastroenterology 143 2012 986 994.e3 quiz e14-e15
125. E.A. Pomfret, K. Washburn, C. Wald, and et al. Report of a national conference on liver allocation in patients with hepatocellular carcinoma in the United States Liver Transpl 16 2010 262 278
126. P.A. Clavien, M. Lesurtel, P.M. Bossuyt, and et al. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report Lancet Oncol 13 2012 e11 e22
127. M. Navasa, and J. Bruix Multifaceted perspective of the waiting list for liver transplantation: the value of pharmacokinetic models Hepatology 51 2010 12 15
128. C. Toso, V. Mazzaferro, J. Bruix, and et al. Toward a better liver graft allocation that accounts for candidates with and without hepatocellular carcinoma Am J Transplant 14 2014 2221 2227
129. P.E. Majno, R. Adam, H. Bismuth, and et al. Influence of preoperative transarterial lipiodol chemoembolization on resection and transplantation for hepatocellular carcinoma in patients with cirrhosis Ann Surg 226 1997 688 701 discussion 701-703
130. F.Y. Yao, N. Mehta, J. Flemming, and et al. Downstaging of hepatocellular cancer before liver transplant: long-term outcome compared to tumors within Milan criteria Hepatology 61 2015 1968 1977
131. M. Ravaioli, G.L. Grazi, F. Piscaglia, and et al. Liver transplantation for hepatocellular carcinoma: results of down-staging in patients initially outside the Milan selection criteria Am J Transplant 8 2008 2547 2557
132. V. Mazzaferro, R. Lencioni, P. Majno, and et al. Early hepatocellular carcinoma on the procrustean bed of ablation, resection, and transplantation Semin Liver Dis 34 2014 415 426
133. Y.K. Cho, J.K. Kim, M.Y. Kim, and et al. Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies Hepatology 49 2009 453 459
134. G. Germani, M. Pleguezuelo, K. Gurusamy, and et al. Clinical outcomes of radiofrequency ablation, percutaneous alcohol and acetic acid injection for hepatocelullar carcinoma: a meta-analysis J Hepatol 52 2010 380 388
135. Z.-W. Peng, Y.-J. Zhang, M.-S. Chen, and et al. Radiofrequency ablation with or without transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma: a prospective randomized trial J Clin Oncol 31 2013 426 432
136. H. Imamura, Y. Matsuyama, E. Tanaka, and et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy J Hepatol 38 2003 200 207
137. J. Bruix, T. Takayama, V. Mazzaferro, and et al. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial Lancet Oncol 16 2015 1344 1354
138. E.K. Geissler, A.A. Schnitzbauer, C. Zülke, and et al. Sirolimus use in liver transplant recipients with hepatocellular carcinoma: a randomized, multicenter, open-label phase 3 trial Transplantation 100 2016 116 125
139. J. Bruix, M. Sala, and J.M. Llovet Chemoembolization for hepatocellular carcinoma Gastroenterology 127 2004 S179 S188
140. J.M. Llovet, M.I. Real, X. Montana, and et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial Lancet 359 2002 1734 1739
141. C.-M. Lo, H. Ngan, W.-K. Tso, and et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma Hepatology 35 2002 1164 1171
142. J.M. Llovet, and J. Bruix Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival Hepatology 37 2003 429 442
143. R. Poon, B.O. Anderson, L.T. Chen, and et al. Management of hepatocellular carcinoma in Asia: consensus statement from the Asian Oncology Summit 2009 Lancet Oncol 10 2009 1111 1118
144. C. Verslype, O. Rosmorduc, and P. Rougier Hepatocellular carcinoma: ESMO-ESDO clinical practice guidelines for diagnosis, treatment and follow-up Ann Oncol 23 suppl 7 2012 vii41 vii48
145. M. Varela, M.I. Real, M. Burrel, and et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics J Hepatol 46 2007 474 481
146. J. Lammer, K. Malagari, T. Vogl, and et al. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study Cardiovasc Interv Radiol 33 2009 41 52
147. R. Golfieri, E. Giampalma, M. Renzulli, and et al. Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma Br J Cancer 111 2014 255 264
148. M. Burrel, M. Reig, A. Forner, and et al. Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using drug eluting beads. Implications for clinical practice and trial design J Hepatol 56 2012 1330 1335
149. K. Malagari, M. Pomoni, H. Moschouris, and et al. Chemoembolization with doxorubicin-eluting beads for unresectable hepatocellular carcinoma: five-year survival analysis Cardiovasc Interv Radiol 35 2012 1119 1128
150. K. Takayasu, S. Arii, M. Kudo, and et al. Superselective transarterial chemoembolization for hepatocellular carcinoma. Validation of treatment algorithm proposed by Japanese guidelines J Hepatol 56 2012 886 892
151. W. Sieghart, F. Hucke, M. Pinter, and et al. The ART of decision making: retreatment with transarterial chemoembolization in patients with hepatocellular carcinoma Hepatology 57 2013 2261 2273
152. L. Kadalayil, R. Benini, L. Pallan, and et al. A simple prognostic scoring system for patients receiving transarterial embolisation for hepatocellular cancer Ann Oncol 24 2013 2565 2570
153. R. Lencioni, L. Crocetti, P. Petruzzi, and et al. Doxorubicin-eluting bead-enhanced radiofrequency ablation of hepatocellular carcinoma: a pilot clinical study J Hepatol 49 2008 217 222
154. R.T.-P. Poon, C. Lau, W.-C. Yu, and et al. High serum levels of vascular endothelial growth factor predict poor response to transarterial chemoembolization in hepatocellular carcinoma: a prospective study Oncol Rep 11 2004 1077 1084
155. R. Lencioni, J.M. Llovet, G. Han, and et al. Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: The SPACE trial J Hepatol 2016 Jan 22 pii: S0168-8278(16)00018-0. http://dx.doi.org/10.1016/j.jhep.2016.01.012. [Epub ahead of print]
156. M. Kudo, G. Han, R.S. Finn, and et al. Brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: a randomized phase III trial Hepatology 60 2014 1697 1707
157. G. Torzilli, J. Belghiti, N. Kokudo, and et al. A snapshot of the effective indications and results of surgery for hepatocellular carcinoma in tertiary referral centers: is it adherent to the EASL/AASLD recommendations? An observational study of the HCC East-West study group Ann. Surg 257 2013 929 937
158. S. Roayaie, G. Jibara, P. Tabrizian, and et al. The role of hepatic resection in the treatment of hepatocellular cancer Hepatology 62 2015 440 451
159. S. Wilhelm, C. Carter, M. Lynch, and et al. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer Nat Rev Drug Discov 5 2006 835 844
160. J.L. Raoul, J. Bruix, T.F. Greten, and et al. Relationship between baseline hepatic status and outcome, and effect of sorafenib on liver function: SHARP trial subanalyses J Hepatol 56 2012 1080 1088
161. A.L. Cheng, Y.K. Kang, Z. Chen, and 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 10 2009 25 34
162. J. Bruix, J.-L. Raoul, M. Sherman, and et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial J Hepatol 57 2012 821 829
163. J.M. Llovet, C.E.A. Peña, C.D. Lathia, and et al. Plasma biomarkers as predictors of outcome in patients with advanced hepatocellular carcinoma Clin Cancer Res 18 2012 2290 2300
164. M. Reig, F. Torres, C. Rodriguez-Lope, and et al. Early dermatologic adverse events predict better outcome in HCC patients treated with sorafenib J Hepatol 61 2014 318 324
165. M. Reig, A. Gazzola, R. Di Donato, and et al. Systemic treatment Best Pract Res Clin Gastroenterol 28 2014 921 935
166. M. Reig, J. Rimola, F. Torres, and et al. Postprogression survival of patients with advanced hepatocellular carcinoma: Rationale for second-line trial design Hepatology 58 2013 2023 2031
167. A.L. Cheng, Y.K. Kang, D.Y. Lin, and et al. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial J Clin Oncol 31 2013 4067 4075
168. P.J. Johnson, S. Qin, J.W. Park, and et al. Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: results from the randomized phase III BRISK-FL study J Clin Oncol 31 2013 3517 3524
169. C. Cainap, S. Qin, W.-T. Huang, and et al. Phase III trial of linifanib versus sorafenib in patients with advanced hepatocellular carcinoma (HCC) (abstr 249) J Clin Oncol 31 suppl 4 2013 249
170. A.X. Zhu, O. Rosmorduc, T.R.J. Evans, and et al. SEARCH: a phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma J Clin Oncol 33 2015 559 566
171. J.M. Llovet, T. Decaens, J.L. Raoul, and et al. Brivanib in patients with advanced hepatocellular carcinoma who were intolerant to sorafenib or for whom sorafenib failed: results from the randomized phase III BRISK-PS study J Clin Oncol 31 2013 3509 3516
172. A.X. Zhu, M. Kudo, E. Assenat, and et al. Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial JAMA 312 2014 57 67
173. A.X. Zhu, J.O. Park, B.-Y. Ryoo, and et al. Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial Lancet Oncol 16 2015 859 870
174. G.K. Abou-Alfa, L. Schwartz, S. Ricci, and et al. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma J Clin Oncol 24 2006 4293 4300
175. M.B. Thomas, R. Chadha, K. Glover, and et al. Phase 2 study of erlotinib in patients with unresectable hepatocellular carcinoma Cancer 110 2007 1059 1067
176. P.A. Philip, M.R. Mahoney, C. Allmer, and et al. Phase II study of erlotinib (OSI-774) in patients with advanced hepatocellular cancer J Clin Oncol 23 2005 6657 6663
177. H.C. Toh, P.-J. Chen, B.I. Carr, and et al. Phase 2 trial of linifanib (ABT-869) in patients with unresectable or metastatic hepatocellular carcinoma Cancer 119 2013 380 387
178. C. Barone, M. Basso, M. Biolato, and et al. A phase II study of sunitinib in advanced hepatocellular carcinoma Dig Liver Dis 45 2013 692 698
179. D. Koeberle, M. Montemurro, P. Samaras, and et al. Continuous sunitinib treatment in patients with advanced hepatocellular carcinoma: a Swiss Group for Clinical Cancer Research (SAKK) and Swiss Association for the Study of the Liver (SASL) multicenter phase II trial (SAKK 77/06) Oncologist 15 2010 285 292
180. A.X. Zhu, D.V. Sahani, D.G. Duda, and et al. Efficacy, safety, and potential biomarkers of sunitinib monotherapy in advanced hepatocellular carcinoma: a phase II study J Clin Oncol 27 2009 3027 3035
181. S. Faivre, E. Raymond, E. Boucher, and et al. Safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma: an open-label, multicentre, phase II study Lancet Oncol 10 2009 794 800
182. J.-W. Park, R.S. Finn, J.S. Kim, and et al. Phase II, open-label study of brivanib as first-line therapy in patients with advanced hepatocellular carcinoma Clin Cancer Res 17 2011 1973 1983
183. S.K. Qin, M.R. Cao, J. Qian, and et al. Clinical study of FOLFOX regimen for the patients with advanced hepatocellular carcinoma [in Chinese] Chin Clin Oncol 10 2005 58 60
184. R.S. Finn, Y.-K. Kang, M. Mulcahy, and et al. Phase II, open-label study of brivanib as second-line therapy in patients with advanced hepatocellular carcinoma Clin Cancer Res 18 2012 2090 2098
185. M. Reig, and J. Bruix Pattern of tumor progression in liver cancer: The missing partner in trial design Hepatology 62 2015 674 676
186. R. Lencioni, and J. Llovet Modified RECIST (mRECIST) assessment for hepatocellular carcinoma Semin Liver Dis 30 2010 52 60
187. A.A. Alizadeh, V. Aranda, A. Bardelli, and et al. Toward understanding and exploiting tumor heterogeneity Nat Med 21 2015 846 853
188. B. Sangro, and R. Salem Transarterial chemoembolization and radioembolization Semin Liver Dis 34 2014 435 443
189. K. Memon, L. Kulik, R.J. Lewandowski, and et al. Radiographic response to locoregional therapy in hepatocellular carcinoma predicts patient survival times Gastroenterology 141 2011 526 535 535.e1-2
190. R. Salem, R.J. Lewandowski, M.F. Mulcahy, and et al. Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes Gastroenterology 138 2010 52 64
191. P. Hilgard, M. Hamami, A.E. Fouly, and et al. Radioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival Hepatology 52 2010 1741 1749
192. B. Sangro, L. Carpanese, R. Cianni, and et al. Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation Hepatology 54 2011 868 878
193. R. Salem, V. Mazzaferro, and B. Sangro Yttrium 90 radioembolization for the treatment of hepatocellular carcinoma: biological lessons, current challenges, and clinical perspectives Hepatology 58 2013 2188 2197
194. B. Sangro, B. Gil-Alzugaray, J. Rodriguez, and et al. Liver disease induced by radioembolization of liver tumors: description and possible risk factors Cancer 112 2008 1538 1546
195. R. Salem, R.J. Lewandowski, L. Kulik, and et al. Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma Gastroenterology 140 2011 497 507.e2
196. V. Mazzaferro, C. Sposito, S. Bhoori, and et al. Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study Hepatology 57 2013 1826 1837
197. A.B. El-Khoueiry, I. Melero, T.S. Crocenzi, and et al. Phase I/II safety and antitumor activity of nivolumab in patients with advanced hepatocellular carcinoma (HCC): CA209-040 J Clin Oncol 33 2015
198. M.F. Sprinzl, and P.R. Galle Immune control in hepatocellular carcinoma development and progression: role of stromal cells Semin Liver Dis 34 2014 376 388
199. W. Yeo, H.C. Chung, S.L. Chan, and et al. Epigenetic therapy using belinostat for patients with unresectable hepatocellular carcinoma: a multicenter phase I/II study with biomarker and pharmacokinetic analysis of tumors from patients in the Mayo Phase II Consortium and the Cancer Therapeutics Res J Clin Oncol 30 2012 3361 3367
200. J. Bruix, K.-H. Han, G. Gores, and et al. Liver cancer: approaching a personalized care J Hepatol 62 2015 S144 S156
201. A. Zhu, R. Ryoo, C. Yen, and et al. Ramucirumab (RAM) as second-line treatment in patients (pts) with advanced hepatocellular carcinoma (HCC): analysis of patients with elevated α-fetoprotein (AFP) from the randomized phase III REACH study J Clin Oncol 33 2015
202. A. Santoro, L. Rimassa, I. Borbath, and et al. Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase 2 study Lancet Oncol 14 2013 55 63
203. J. Heo, T. Reid, L. Ruo, and et al. Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer Nat Med 19 2013 329 336
204. Jennerex presents positive clinical data from phase 2 trial of JX-594 in sorafenib-refractory liver cancer patients. September 17, 2012. http://www.prnewswire.com/news-releases/jennerex-presents-positive-clinical-data-from-phase-2-trial-of-jx-594-in-sorafenib-refractory-liver-cancer-patients-170006966.html.