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Liver Transplantation for Hepatocellular Carcinoma

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Hepatocellular Carcinoma

Part of the book series: Current Clinical Oncology ((CCO))

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Abstract

Hepatocellular carcinoma (HCC) is a major health problem worldwide because of the association of HCC with chronic liver injury and inflammation due to viral, non-viral and genetic etiologies [1]. While historically HCC was often considered for palliative therapy, new curative alternatives have emerged such as liver resection, loco-regional therapies and liver transplantation (LT).

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Abbreviations

AFP:

Alpha-fetoprotein

AFP-L3:

Lens culinaris agglutinin A-reactive fraction of alpha fetoprotein

CNI:

Calcineurin inhibitor

DCP:

Des-gamma-carboxy prothrombin

DDLT:

Deceased donor liver transplantation

HCC:

Hepatocellular carcinoma

LDLT:

Living donor liver transplantation

LT:

Liver transplantation

LRT:

Locoregional tumor treatment

MC:

Milan criteria

MiVI:

Microvascular invasion

m-TOR:

Mammalian target of rapamycin

RFA:

Radiofrequency ablation

SRL:

Sirolimus

TACE:

Transarterial chemoembolization

TTV:

Total tumor volume

UCSF:

University of California San Francisco

VEGF:

Vascular endothelial growth factor

References

  1. El-Serag HB, Kanwal F. Epidemiology of hepatocellular carcinoma in the United States: where are we? Where do we go? Hepatology. 2014;60(5):1767–75.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Iwatsuki S, Gordon RD, Shaw BW Jr, Starzl TE. Role of liver transplantation in cancer therapy. Ann Surg. 1985;202(4):401–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334(11):693–9.

    Article  CAS  PubMed  Google Scholar 

  4. Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A, et al. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol. 2012;13(1):e11–22.

    Article  PubMed  Google Scholar 

  5. ELTR - European Liver Transplant Registry [Internet]. [January 2011]. Available from: http://www.eltr.org.

  6. OPTN - Organ Procurement and Transplantation Network [Internet]. [January 2011]. Available from: http://www.ustransplant.org/annual_reports.

  7. Volk ML, Vijan S, Marrero JA. A novel model measuring the harm of transplanting hepatocellular carcinoma exceeding Milan criteria. Am J Transplant. 2008;8(4):839–46.

    Article  CAS  PubMed  Google Scholar 

  8. Mazzaferro V, Bhoori S, Sposito C, Bongini M, Langer M, Miceli R, et al. Milan criteria in liver transplantation for hepatocellular carcinoma: an evidence-based analysis of 15 years of experience. Liver Transpl. 2011;17(Suppl 2):S44–57.

    Article  PubMed  Google Scholar 

  9. Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33(6):1394–403.

    Article  CAS  PubMed  Google Scholar 

  10. 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(11):2587–96.

    Article  CAS  PubMed  Google Scholar 

  11. Duffy JP, Vardanian A, Benjamin E, Watson M, Farmer DG, Ghobrial RM, et al. Liver transplantation criteria for hepatocellular carcinoma should be expanded: a 22-year experience with 467 patients at UCLA. Ann Surg. 2007;246(3):502–9; discussion 9-11.

    Google Scholar 

  12. Chen JW, Kow L, Verran DJ, McCall JL, Munn S, Balderson GA, et al. Poorer survival in patients whose explanted hepatocellular carcinoma (HCC) exceeds Milan or UCSF Criteria. An analysis of liver transplantation in HCC in Australia and New Zealand. HPB (Oxford). 2009;11(1):81–9.

    Google Scholar 

  13. Lee SG, Hwang S, Moon DB, Ahn CS, Kim KH, Sung KB, et al. Expanded indication criteria of living donor liver transplantation for hepatocellular carcinoma at one large-volume center. Liver Transpl. 2008;14(7):935–45.

    Article  PubMed  Google Scholar 

  14. Bonadio I, Colle I, Geerts A, Smeets P, Berardi G, Praet M, et al. Liver transplantation for hepatocellular carcinoma comparing the Milan, UCSF, and Asan criteria: long-term follow-up of a Western single institutional experience. Clin Transplant. 2015;29(5):425–33.

    Article  PubMed  Google Scholar 

  15. Mazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiavo M, Mariani L, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10(1):35–43.

    Article  PubMed  Google Scholar 

  16. D’Amico F, Schwartz M, Vitale A, Tabrizian P, Roayaie S, Thung S, et al. Predicting recurrence after liver transplantation in patients with hepatocellular carcinoma exceeding the up-to-seven criteria. Liver Transpl. 2009;15(10):1278–87.

    Article  PubMed  Google Scholar 

  17. Toyoda H, Kumada T, Tada T, Sone Y, Kaneoka Y, Maeda A. Tumor markers for Hepatocellular Carcinoma: simple and significant predictors of outcome in patients with HCC. Liver cancer. 2015;4(2):126–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. European Association For The Study Of The. L, European Organisation For R, Treatment Of C. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56(4):908–43.

    Article  Google Scholar 

  19. Merani S, Majno P, Kneteman NM, Berney T, Morel P, Mentha G, et al. The impact of waiting list alpha-fetoprotein changes on the outcome of liver transplant for hepatocellular carcinoma. J Hepatol. 2011;55(4):814–9.

    Article  CAS  PubMed  Google Scholar 

  20. Toso C, Asthana S, Bigam DL, Shapiro AM, Kneteman NM. Reassessing selection criteria prior to liver transplantation for hepatocellular carcinoma utilizing the scientific registry of transplant recipients database. Hepatology. 2009;49(3):832–8.

    Article  PubMed  Google Scholar 

  21. Lai Q, Avolio AW, Manzia TM, Sorge R, Agnes S, Tisone G, et al. Combination of biological and morphological parameters for the selection of patients with hepatocellular carcinoma waiting for liver transplantation. Clin Transplant. 2012;26(2):E125–31.

    Article  PubMed  Google Scholar 

  22. Zheng SS, Xu X, Wu J, Chen J, Wang WL, Zhang M, et al. Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation. 2008;85(12):1726–32.

    Article  CAS  PubMed  Google Scholar 

  23. Wong LL, Naugler WE, Schwartz J, Scott DL, Bhattacharya R, Reyes J, et al. Impact of locoregional therapy and alpha-fetoprotein on outcomes in transplantation for liver cancer: a UNOS Region 6 pooled analysis. Clin Transplant. 2013;27(1):E72–9.

    Article  PubMed  Google Scholar 

  24. McHugh PP, Gilbert J, Vera S, Koch A, Ranjan D, Gedaly R. Alpha-fetoprotein and tumour size are associated with microvascular invasion in explanted livers of patients undergoing transplantation with hepatocellular carcinoma. HPB (Oxford). 2010;12(1):56–61.

    Article  Google Scholar 

  25. Grat M, Kornasiewicz O, Lewandowski Z, Holowko W, Grat K, Kobryn K, et al. Combination of morphologic criteria and alpha-fetoprotein in selection of patients with hepatocellular carcinoma for liver transplantation minimizes the problem of posttransplant tumor recurrence. World J Surg. 2014;38(10):2698–707.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Harimoto N, Shirabe K, Nakagawara H, Toshima T, Yamashita Y, Ikegami T, et al. Prognostic factors affecting survival at recurrence of hepatocellular carcinoma after living-donor liver transplantation: with special reference to neutrophil/lymphocyte ratio. Transplantation. 2013;96(11):1008–12.

    Article  CAS  PubMed  Google Scholar 

  27. Vibert E, Azoulay D, Hoti E, Iacopinelli S, Samuel D, Salloum C, et al. Progression of alphafetoprotein before liver transplantation for hepatocellular carcinoma in cirrhotic patients: a critical factor. Am J Transplant. 2010;10(1):129–37.

    Article  CAS  PubMed  Google Scholar 

  28. Duvoux C, Roudot-Thoraval F, Decaens T, Pessione F, Badran H, Piardi T, et al. Liver transplantation for hepatocellular carcinoma: a model including alpha-fetoprotein improves the performance of Milan criteria. Gastroenterology. 2012;143(4):986–94 e3; quiz e14-5.

    Google Scholar 

  29. Hameed B, Mehta N, Sapisochin G, Roberts JP, Yao FY. Alpha-fetoprotein level > 1000 ng/mL as an exclusion criterion for liver transplantation in patients with hepatocellular carcinoma meeting the Milan criteria. Liver Transpl. 2014;20(8):945–51.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Chaiteerakij R, Zhang X, Addissie BD, Mohamed EA, Harmsen WS, Theobald PJ, et al. Combinations of biomarkers and Milan criteria for predicting hepatocellular carcinoma recurrence after liver transplantation. Liver Transpl. 2015;21(5):599–606.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Shindoh J, Sugawara Y, Nagata R, Kaneko J, Tamura S, Aoki T, et al. Evaluation methods for pretransplant oncologic markers and their prognostic impacts in patient undergoing living donor liver transplantation for hepatocellular carcinoma. Transpl Int. 2014;27(4):391–8.

    Article  CAS  PubMed  Google Scholar 

  32. Toyoda H, Kumada T, Tada T, Niinomi T, Ito T, Kaneoka Y, et al. Prognostic significance of a combination of pre- and post-treatment tumor markers for hepatocellular carcinoma curatively treated with hepatectomy. J Hepatol. 2012;57(6):1251–7.

    Article  CAS  PubMed  Google Scholar 

  33. Majno P, Lencioni R, Mornex F, Girard N, Poon RT, Cherqui D. Is the treatment of hepatocellular carcinoma on the waiting list necessary? Liver Transpl. 2011;17(Suppl 2):S98–108.

    Article  PubMed  Google Scholar 

  34. Melloul E, Lesurtel M, Carr BI, Clavien PA. Developments in liver transplantation for hepatocellular carcinoma. Semin Oncol. 2012;39(4):510–21.

    Article  PubMed  Google Scholar 

  35. Golfieri R, Cappelli A, Cucchetti A, Piscaglia F, Carpenzano M, Peri E, et al. Efficacy of selective transarterial chemoembolization in inducing tumor necrosis in small (<5 cm) hepatocellular carcinomas. Hepatology. 2011;53(5):1580–9.

    Article  PubMed  Google Scholar 

  36. Kwan SW, Fidelman N, Ma E, Kerlan RK Jr, Yao FY. Imaging predictors of the response to transarterial chemoembolization in patients with hepatocellular carcinoma: a radiological-pathological correlation. Liver Transpl. 2012;18(6):727–36.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Lu DS, Yu NC, Raman SS, Lassman C, Tong MJ, Britten C, et al. Percutaneous radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation. Hepatology. 2005;41(5):1130–7.

    Article  PubMed  Google Scholar 

  38. Mazzaferro V, Battiston C, Perrone S, Pulvirenti A, Regalia E, Romito R, et al. Radiofrequency ablation of small hepatocellular carcinoma in cirrhotic patients awaiting liver transplantation: a prospective study. Ann Surg. 2004;240(5):900–9.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Pompili M, Mirante VG, Rondinara G, Fassati LR, Piscaglia F, Agnes S, et al. Percutaneous ablation procedures in cirrhotic patients with hepatocellular carcinoma submitted to liver transplantation: assessment of efficacy at explant analysis and of safety for tumor recurrence. Liver Transpl. 2005;11(9):1117–26.

    Article  PubMed  Google Scholar 

  40. Majno PE, Adam R, Bismuth H, Castaing D, Ariche A, Krissat J, et al. Influence of preoperative transarterial lipiodol chemoembolization on resection and transplantation for hepatocellular carcinoma in patients with cirrhosis. Ann Surg. 1997;226(6):688–701; discussion-3.

    Google Scholar 

  41. Lesurtel M, Mullhaupt B, Pestalozzi BC, Pfammatter T, Clavien PA. Transarterial chemoembolization as a bridge to liver transplantation for hepatocellular carcinoma: an evidence-based analysis. Am J Transplant. 2006;6(11):2644–50.

    Article  CAS  PubMed  Google Scholar 

  42. Millonig G, Graziadei IW, Freund MC, Jaschke W, Stadlmann S, Ladurner R, et al. Response to preoperative chemoembolization correlates with outcome after liver transplantation in patients with hepatocellular carcinoma. Liver Transpl. 2007;13(2):272–9.

    Article  PubMed  Google Scholar 

  43. Tsochatzis E, Garcovich M, Marelli L, Papastergiou V, Fatourou E, Rodriguez-Peralvarez ML, et al. Transarterial embolization as neo-adjuvant therapy pretransplantation in patients with hepatocellular carcinoma. Liver Int. 2013;33(6):944–9.

    Article  CAS  PubMed  Google Scholar 

  44. Terzi E, Ray Kim W, Sanchez W, Charlton MR, Schmeltzer P, Gores GJ, et al. Impact of multiple transarterial chemoembolization treatments on hepatocellular carcinoma for patients awaiting liver transplantation. Liver Transpl. 2015;21(2):248–57.

    Article  PubMed  Google Scholar 

  45. Porrett PM, Peterman H, Rosen M, Sonnad S, Soulen M, Markmann JF, et al. Lack of benefit of pre-transplant locoregional hepatic therapy for hepatocellular cancer in the current MELD era. Liver Transpl. 2006;12(4):665–73.

    Article  PubMed  Google Scholar 

  46. Riaz A, Kulik L, Lewandowski RJ, Ryu RK, Giakoumis Spear G, Mulcahy MF, et al. Radiologic-pathologic correlation of hepatocellular carcinoma treated with internal radiation using yttrium-90 microspheres. Hepatology. 2009;49(4):1185–93.

    Article  PubMed  Google Scholar 

  47. Agopian VG, Morshedi MM, McWilliams J, Harlander-Locke MP, Markovic D, Zarrinpar A, et al. Complete pathologic response to pretransplant locoregional therapy for hepatocellular carcinoma defines cancer cure after liver transplantation: analysis of 501 consecutively treated patients. Ann Surg. 2015;262(3):536–45; discussion 43–5.

    Google Scholar 

  48. Llovet JM, Mas X, Aponte JJ, Fuster J, Navasa M, Christensen E, et al. Cost effectiveness of adjuvant therapy for hepatocellular carcinoma during the waiting list for liver transplantation. Gut. 2002;50(1):123–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Cherqui D, Laurent A, Mocellin N, Tayar C, Luciani A, Van Nhieu JT, et al. Liver resection for transplantable hepatocellular carcinoma: long-term survival and role of secondary liver transplantation. Ann Surg. 2009;250(5):738–46.

    Article  PubMed  Google Scholar 

  50. Fuks D, Dokmak S, Paradis V, Diouf M, Durand F, Belghiti J. Benefit of initial resection of hepatocellular carcinoma followed by transplantation in case of recurrence: an intention-to-treat analysis. Hepatology. 2012;55(1):132–40.

    Article  PubMed  Google Scholar 

  51. Sharr WW, Chan SC, Lo CM. Section 3. Current status of downstaging of hepatocellular carcinoma before liver transplantation. Transplantation. 2014;97(Suppl 8):S10–7.

    Article  PubMed  Google Scholar 

  52. Kulik L, Salem R. Downstaging: Looking for answers, generating more questions? Liver Transpl. 2015;21(9):1117–9.

    Article  PubMed  Google Scholar 

  53. Yao FY, Mehta N, Flemming J, Dodge J, Hameed B, Fix O, et al. Downstaging of hepatocellular cancer before liver transplant: long-term outcome compared to tumors within Milan criteria. Hepatology. 2015;61(6):1968–77.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Parikh ND, Waljee AK, Singal AG. Downstaging hepatocellular carcinoma: A systematic review and pooled analysis. Liver Transpl. 2015;21(9):1142–52.

    Article  PubMed  Google Scholar 

  55. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol. 2001;35(3):421–30.

    Article  CAS  PubMed  Google Scholar 

  56. Yao FY, Kerlan RK Jr, Hirose R, Davern TJ 3rd, Bass NM, Feng S, et al. Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis. Hepatology. 2008;48(3):819–27.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Lewandowski RJ, Kulik LM, Riaz A, Senthilnathan S, Mulcahy MF, Ryu RK, et al. A comparative analysis of transarterial downstaging for hepatocellular carcinoma: chemoembolization versus radioembolization. Am J Transplant. 2009;9(8):1920–8.

    Article  CAS  PubMed  Google Scholar 

  58. Ravaioli M, Grazi GL, Piscaglia F, Trevisani F, Cescon M, Ercolani G, et al. Liver transplantation for hepatocellular carcinoma: results of down-staging in patients initially outside the Milan selection criteria. Am J Transplant. 2008;8(12):2547–57.

    Article  CAS  PubMed  Google Scholar 

  59. Orlacchio A, Chegai F, Merolla S, Francioso S, Giudice CD, Angelico M, et al. Downstaging disease in patients with hepatocellular carcinoma outside up-to-seven criteria: strategies using degradable starch microspheres transcatheter arterial chemo-embolization. World J Hepatol. 2015;7(12):1694–700.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Barr ML, Belghiti J, Villamil FG, Pomfret EA, Sutherland DS, Gruessner RW, et al. A report of the Vancouver Forum on the care of the live organ donor: lung, liver, pancreas, and intestine data and medical guidelines. Transplantation. 2006;81(10):1373–85.

    Article  PubMed  Google Scholar 

  61. Trotter JF, Adam R, Lo CM, Kenison J. Documented deaths of hepatic lobe donors for living donor liver transplantation. Liver Transpl. 2006;12(10):1485–8.

    Article  PubMed  Google Scholar 

  62. Miller CM. Ethical dimensions of living donation: experience with living liver donation. Transplant Rev (Orlando). 2008;22(3):206–9.

    Article  Google Scholar 

  63. Cronin DC 2nd, Millis JM. Living donor liver transplantation: the ethics and the practice. Hepatology. 2008;47(1):11–3.

    Article  PubMed  Google Scholar 

  64. Cronin DC 2nd, Millis JM, Siegler M. Transplantation of liver grafts from living donors into adults–too much, too soon. N Engl J Med. 2001;344(21):1633–7.

    Article  PubMed  Google Scholar 

  65. Pomfret EA, Lodge JP, Villamil FG, Siegler M. Should we use living donor grafts for patients with hepatocellular carcinoma? Ethical considerations. Liver Transpl. 2011;17(Suppl 2):S128–32.

    Article  PubMed  Google Scholar 

  66. Siegler M, Simmerling MC, Siegler JH, Cronin DC 2nd. Recipient deaths during donor surgery: a new ethical problem in living donor liver transplantation (LDLT). Liver Transpl. 2006;12(3):358–60.

    Article  PubMed  Google Scholar 

  67. Di Sandro S, Slim AO, Giacomoni A, Lauterio A, Mangoni I, Aseni P, et al. Living donor liver transplantation for hepatocellular carcinoma: long-term results compared with deceased donor liver transplantation. Transplant Proc. 2009;41(4):1283–5.

    Article  PubMed  Google Scholar 

  68. Fisher RA, Kulik LM, Freise CE, Lok AS, Shearon TH, Brown RS Jr, et al. Hepatocellular carcinoma recurrence and death following living and deceased donor liver transplantation. Am J Transplant. 2007;7(6):1601–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Hwang S, Lee SG, Joh JW, Suh KS, Kim DG. Liver transplantation for adult patients with hepatocellular carcinoma in Korea: comparison between cadaveric donor and living donor liver transplantations. Liver Transpl. 2005;11(10):1265–72.

    Article  PubMed  Google Scholar 

  70. Kulik L, Abecassis M. Living donor liver transplantation for hepatocellular carcinoma. Gastroenterology. 2004;127(5 Suppl 1):S277–82.

    Article  PubMed  Google Scholar 

  71. Lo CM, Fan ST, Liu CL, Chan SC, Ng IO, Wong J. Living donor versus deceased donor liver transplantation for early irresectable hepatocellular carcinoma. Br J Surg. 2007;94(1):78–86.

    Article  CAS  PubMed  Google Scholar 

  72. Vakili K, Pomposelli JJ, Cheah YL, Akoad M, Lewis WD, Khettry U, et al. Living donor liver transplantation for hepatocellular carcinoma: increased recurrence but improved survival. Liver Transpl. 2009;15(12):1861–6.

    Article  PubMed  Google Scholar 

  73. Liang W, Wu L, Ling X, Schroder PM, Ju W, Wang D, et al. Living donor liver transplantation versus deceased donor liver transplantation for hepatocellular carcinoma: a meta-analysis. Liver Transpl. 2012;18(10):1226–36.

    Article  PubMed  Google Scholar 

  74. Grant RC, Sandhu L, Dixon PR, Greig PD, Grant DR, McGilvray ID. Living vs. deceased donor liver transplantation for hepatocellular carcinoma: a systematic review and meta-analysis. Clin Transplant. 2013;27(1):140–7.

    Article  PubMed  Google Scholar 

  75. Kulik LM, Fisher RA, Rodrigo DR, Brown RS Jr, Freise CE, Shaked A, et al. Outcomes of living and deceased donor liver transplant recipients with hepatocellular carcinoma: results of the A2ALL cohort. Am J Transplant. 2012;12(11):2997–3007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Grant D, Fisher RA, Abecassis M, McCaughan G, Wright L, Fan ST. Should the liver transplant criteria for hepatocellular carcinoma be different for deceased donation and living donation? Liver Transpl. 2011;17(Suppl 2):S133–8.

    Article  PubMed  Google Scholar 

  77. Chen GH, Lu MQ, Cai CJ, Yang Y, He XS, Zhu XF. Clinical study of adjuvant individualized chemotherapy for hepatocellular carcinoma after liver transplantation. Zhonghua Wai Ke Za Zhi. 2004;42(17):1040–3.

    PubMed  Google Scholar 

  78. Cherqui D, Piedbois P, Pierga JY, Duvoux C, Vavasseur D, Tran Van-Nhieu J, et al. Multimodal adjuvant treatment and liver transplantation for advanced hepatocellular carcinoma. A pilot study. Cancer. 1994;73(11):2721–6.

    Article  CAS  PubMed  Google Scholar 

  79. Hsieh CB, Chou SJ, Shih ML, Chu HC, Chu CH, Yu JC, et al. Preliminary experience with gemcitabine and cisplatin adjuvant chemotherapy after liver transplantation for hepatocellular carcinoma. Eur J Surg Oncol. 2008;34(8):906–10.

    Article  PubMed  Google Scholar 

  80. Olthoff KM, Rosove MH, Shackleton CR, Imagawa DK, Farmer DG, Northcross P, et al. Adjuvant chemotherapy improves survival after liver transplantation for hepatocellular carcinoma. Ann Surg. 1995;221(6):734–41; discussion 1–43.

    Google Scholar 

  81. Roayaie S, Frischer JS, Emre SH, Fishbein TM, Sheiner PA, Sung M, et al. Long-term results with multimodal adjuvant therapy and liver transplantation for the treatment of hepatocellular carcinomas larger than 5 centimeters. Ann Surg. 2002;235(4):533–9.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Stone MJ, Klintmalm GB, Polter D, Husberg BS, Mennel RG, Ramsay MA, et al. Neoadjuvant chemotherapy and liver transplantation for hepatocellular carcinoma: a pilot study in 20 patients. Gastroenterology. 1993;104(1):196–202.

    CAS  PubMed  Google Scholar 

  83. Sun J, Hou BH, Jian ZX, Ou YL, Ou JR. Value of perioperative adjuvant therapy in liver transplantation for advanced hepatocellular carcinoma. Nan Fang Yi Ke Da Xue Xue Bao. 2007;27(4):471–3.

    PubMed  Google Scholar 

  84. Zhang ZH, Ma LW, Song SB, Xiu DR, Wang JJ, Yang XX, et al. Adjuvant chemotherapy after orthotopic liver transplantation for advanced hepatocellular carcinoma. Zhonghua Zhong Liu Za Zhi. 2005;27(1):45–7.

    PubMed  Google Scholar 

  85. Li N, Zhou J, Weng D, Zhang C, Li L, Wang B, et al. Adjuvant adenovirus-mediated delivery of herpes simplex virus thymidine kinase administration improves outcome of liver transplantation in patients with advanced hepatocellular carcinoma. Clin Cancer Res. 2007;13(19):5847–54.

    Article  CAS  PubMed  Google Scholar 

  86. Pokorny H, Gnant M, Rasoul-Rockenschaub S, Gollackner B, Steiner B, Steger G, et al. Does additional doxorubicin chemotherapy improve outcome in patients with hepatocellular carcinoma treated by liver transplantation? Am J Transplant. 2005;5(4 Pt 1):788–94.

    Article  CAS  PubMed  Google Scholar 

  87. Soderdahl G, Backman L, Isoniemi H, Cahlin C, Hockerstedt K, Broome U, et al. A prospective, randomized, multi-centre trial of systemic adjuvant chemotherapy versus no additional treatment in liver transplantation for hepatocellular carcinoma. Transpl Int. 2006;19(4):288–94.

    Article  PubMed  CAS  Google Scholar 

  88. Zhang Q, Chen H, Li Q, Zang Y, Chen X, Zou W, et al. Combination adjuvant chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin after liver transplantation for hepatocellular carcinoma: a preliminary open-label study. Invest New Drugs. 2011;29(6):1360–9.

    Article  CAS  PubMed  Google Scholar 

  89. Xu J, Shen ZY, Chen XG, Zhang Q, Bian HJ, Zhu P, et al. A randomized controlled trial of Licartin for preventing hepatoma recurrence after liver transplantation. Hepatology. 2007;45(2):269–76.

    Article  CAS  PubMed  Google Scholar 

  90. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–90.

    Article  CAS  PubMed  Google Scholar 

  91. Huang L, Li GM, Zhu JY, Li Z, Li T, Leng XS. Efficacy of sorafenib after liver transplantation in patients with primary hepatic carcinoma exceeding the Milan criteria: a preliminary study. Onco Targets Ther. 2012;5:457–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Teng CL, Hwang WL, Chen YJ, Chang KH, Cheng SB. Sorafenib for hepatocellular carcinoma patients beyond Milan criteria after orthotopic liver transplantation: a case control study. World J Surg Oncol. 2012;10:41.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Yan J, Tan C, Gu F, Jiang J, Xu M, Huang X, et al. Sorafenib delays recurrence and metastasis after liver transplantation in a rat model of hepatocellular carcinoma with high expression of phosphorylated extracellular signal-regulated kinase. Liver Transpl. 2013;19(5):507–20.

    Article  PubMed  Google Scholar 

  94. Bruix J, Takayama T, Mazzaferro V, Chau GY, Yang J, Kudo M, et al. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2015;16(13):1344–54.

    Article  CAS  PubMed  Google Scholar 

  95. Kornberg A, Kupper B, Tannapfel A, Katenkamp K, Thrum K, Habrecht O, et al. Long-term survival after recurrent hepatocellular carcinoma in liver transplant patients: clinical patterns and outcome variables. Eur J Surg Oncol. 2010;36(3):275–80.

    Article  CAS  PubMed  Google Scholar 

  96. Fung JJ, Jain A, Kwak EJ, Kusne S, Dvorchik I, Eghtesad B. De novo malignancies after liver transplantation: a major cause of late death. Liver Transpl. 2001;7(11 Suppl 1):S109–18.

    Article  CAS  PubMed  Google Scholar 

  97. Guba M, Graeb C, Jauch KW, Geissler EK. Pro- and anti-cancer effects of immunosuppressive agents used in organ transplantation. Transplantation. 2004;77(12):1777–82.

    Article  CAS  PubMed  Google Scholar 

  98. Villanueva A, Chiang DY, Newell P, Peix J, Thung S, Alsinet C, et al. Pivotal role of mTOR signaling in hepatocellular carcinoma. Gastroenterology. 2008;135(6):1972–83, 83 e1-11.

    Google Scholar 

  99. Hojo M, Morimoto T, Maluccio M, Asano T, Morimoto K, Lagman M, et al. Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature. 1999;397(6719):530–4.

    Article  CAS  PubMed  Google Scholar 

  100. Schumacher G, Oidtmann M, Rosewicz S, Langrehr J, Jonas S, Mueller AR, et al. Sirolimus inhibits growth of human hepatoma cells in contrast to tacrolimus which promotes cell growth. Transplant Proc. 2002;34(5):1392–3.

    Article  CAS  PubMed  Google Scholar 

  101. Semela D, Piguet AC, Kolev M, Schmitter K, Hlushchuk R, Djonov V, et al. Vascular remodeling and antitumoral effects of mTOR inhibition in a rat model of hepatocellular carcinoma. J Hepatol. 2007;46(5):840–8.

    Article  CAS  PubMed  Google Scholar 

  102. Soll C, Clavien PA. Inhibition of mammalian target of rapamycin: two goals with one shot? J Hepatol. 2011;54(1):182–3.

    Article  PubMed  Google Scholar 

  103. Chinnakotla S, Davis GL, Vasani S, Kim P, Tomiyama K, Sanchez E, et al. Impact of sirolimus on the recurrence of hepatocellular carcinoma after liver transplantation. Liver Transpl. 2009;15(12):1834–42.

    Article  PubMed  Google Scholar 

  104. Toso C, Meeberg GA, Bigam DL, Oberholzer J, Shapiro AM, Gutfreund K, et al. De novo sirolimus-based immunosuppression after liver transplantation for hepatocellular carcinoma: long-term outcomes and side effects. Transplantation. 2007;83(9):1162–8.

    Article  CAS  PubMed  Google Scholar 

  105. Toso C, Merani S, Bigam DL, Shapiro AM, Kneteman NM. Sirolimus-based immunosuppression is associated with increased survival after liver transplantation for hepatocellular carcinoma. Hepatology. 2010;51(4):1237–43.

    Article  CAS  PubMed  Google Scholar 

  106. Vivarelli M, Dazzi A, Zanello M, Cucchetti A, Cescon M, Ravaioli M, et al. Effect of different immunosuppressive schedules on recurrence-free survival after liver transplantation for hepatocellular carcinoma. Transplantation. 2010;89(2):227–31.

    Article  CAS  PubMed  Google Scholar 

  107. Zhou J, Wang Z, Wu ZQ, Qiu SJ, Yu Y, Huang XW, et al. Sirolimus-based immunosuppression therapy in liver transplantation for patients with hepatocellular carcinoma exceeding the Milan criteria. Transplant Proc. 2008;40(10):3548–53.

    Article  CAS  PubMed  Google Scholar 

  108. Zimmerman MA, Ghobrial RM, Tong MJ, Hiatt JR, Cameron AM, Hong J, et al. Recurrence of hepatocellular carcinoma following liver transplantation: a review of preoperative and postoperative prognostic indicators. Arch Surg. 2008;143(2):182–8; discussion 8.

    Google Scholar 

  109. Liang W, Wang D, Ling X, Kao AA, Kong Y, Shang Y, et al. Sirolimus-based immunosuppression in liver transplantation for hepatocellular carcinoma: a meta-analysis. Liver Transpl. 2012;18(1):62–9.

    Article  PubMed  Google Scholar 

  110. Menon KV, Hakeem AR, Heaton ND. Meta-analysis: recurrence and survival following the use of sirolimus in liver transplantation for hepatocellular carcinoma. Aliment Pharmacol Ther. 2013;37(4):411–9.

    Article  CAS  PubMed  Google Scholar 

  111. Nocera A, Andorno E, Tagliamacco A, Morelli N, Bottino G, Ravazzoni F, et al. Sirolimus therapy in liver transplant patients: an initial experience at a single center. Transplant Proc. 2008;40(6):1950–2.

    Article  CAS  PubMed  Google Scholar 

  112. Cholongitas E, Mamou C, Rodriguez-Castro KI, Burra P. Mammalian target of rapamycin inhibitors are associated with lower rates of hepatocellular carcinoma recurrence after liver transplantation: a systematic review. Transpl Int. 2014;27(10):1039–49.

    Article  CAS  PubMed  Google Scholar 

  113. Schnitzbauer AA, Zuelke C, Graeb C, Rochon J, Bilbao I, Burra P, et al. A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma. BMC Cancer. 2010;10:190.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Swiss Hepato-Pancreato-Biliary (HPB) and Transplantation Centers, Department of Surgery, University Hospital of Zurich, Raemistrasse, 100, 8091, Zurich, Switzerland

    Georg Györi, Pierre-Alain Clavien & Mickaël Lesurtel

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  1. Georg Györi
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  2. Pierre-Alain Clavien
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  3. Mickaël Lesurtel
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Correspondence to Mickaël Lesurtel .

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  1. Dokuz Eylul University, Izmir Biomedicine and Genome Center Dokuz Eylul University, Izmir, Izmir, Turkey

    Brian I. Carr

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Györi, G., Clavien, PA., Lesurtel, M. (2016). Liver Transplantation for Hepatocellular Carcinoma. In: Carr, B. (eds) Hepatocellular Carcinoma. Current Clinical Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-34214-6_32

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