Abstract
Currently, liver transplantation stands as the best treatment modality for early-stage hepatocellular carcinoma in patients with decompensated cirrhosis, giving patients the opportunity to be free from the potentially lethal complications from both cancer and their advanced underlying liver disease. Following a historical period characterized by high hepatocellular carcinoma recurrence rates following transplantation of patients with advanced stage disease, introduction of the “Milan criteria” encouraged a focus on early stage hepatocellular carcinoma and improved patient and oncologic outcomes were achieved. Data are emerging that patients with tumor size and tumor number slightly in excess of those proposed in the Conventional Milan Criteria share equivalent survivals with traditional early stage patients and should also be considered for liver transplantation. In settings where the number of patients with hepatocellular carcinoma and indications for transplant exceed the number of cadaveric liver allografts, alternative strategies are requisite. These include more liberal use of liver resection, interventional and systemic treatments, and living-related liver transplantation. The field has seen tremendous development and is now under considerable pressure due to epidemic rates of hepatocellular carcinoma in both hepatitis and fatty liver disease-induced cirrhotics. In this setting, multiple controversies in the field require resolution by clinical trial and/or consensus.
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References
Starzl TE, Marchioro TL, Vonkaulla KN, Hermann G, Brittain RS, Waddell WR (1963) Homotransplantation of the liver in humans. Surg Gynecol Obstet 117:659–676
Starzl TE (1992) The puzzle people: memoirs of a transplant surgeon. University of Pittsburg Press, Pittsburgh, PA
Starzl TE, Iwatsuki S, Van Thiel DH et al (1982) Evolution of liver transplantation. Hepatology 2:614–636
Iwatsuki S, Gordon RD, Shaw BW, Jr, Starzl TE (1985) Role of liver transplantation in cancer therapy. Ann Surg 202:401–407
Klintmalm GB, Stone MJ (1990) Liver transplantation for malignancy. Transpl Rev 4:52–58
Ringe B, Pichlmayr R, Wittekind C, Tusch G (1991) Surgical treatment of hepatocellular carcinoma: experience with liver resection and transplantation in 198 patients. World J Surg 15:270–285
Mazzaferro V, Regalia E, Doci R et al (1996) Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334:693–699
Yoo HY, Patt CH, Geschwind JF, Thuluvath PJ (2003) The outcome of liver transplantation in patients with hepatocellular carcinoma in the United States between 1988 and 2001: 5-year survival has improved significantly with time. J Clin Oncol 21:4329–4335
Sala M, Varela M, Bruix J (2004) Selection of candidates with HCC for transplantation in the MELD era. Liver Transpl 10(10 Suppl 2):S4–S9
Yao FY, Ferrell L, Bass NM et al (2001) Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 33:1394–1403
Shetty K, Timmins K, Brensinger C et al (2004) Liver transplantation for hepatocellular carcinoma validation of present selection criteria in predicting outcome. Liver Transpl 10:911–918
Hemming AW, Cattral MS, Reed AI, Van Der Werf WJ, Greig PD, Howard RJ (2001) Liver transplantation for hepatocellular carcinoma. Ann Surg 233:652–659
Jonas S, Bechstein WO, Steinmuller T et al (2001) Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis. Hepatology 33:1080–1086
Bruix J, Fuster J, Llovet JM (2003) Liver transplantation for hepatocellular carcinoma: Foucault pendulum versus evidence-based decision. Liver Transpl 9:700–702
McGlynn KA, Tarone RE, El-Serag HB (2006) A comparison of trends in the incidence of hepatocellular carcinoma and intrahepatic cholangiocarcinoma in the United States. Cancer Epidemiol Biomarkers Prev 15:1198–1203
El-Serag HB (2002) Hepatocellular carcinoma and hepatitis C in the United States. Hepatology 36(5 Suppl 1):S74–S83
Bruix J, Sherman M (2005) Management of hepatocellular carcinoma. Hepatology 42:1208–1236
Freeman RB, Jr, Wiesner RH, Harper A et al (2002) The new liver allocation system: moving toward evidence-based transplantation policy. Liver Transpl 8:851–858
Ioannou GN, Perkins JD, Carithers RL, Jr (2008) Liver transplantation for hepatocellular carcinoma: impact of the MELD allocation system and predictors of survival. Gastroenterology 134:1342–1351
Poon RT, Fan ST, Lo CM, Liu CL, Wong J (2007) Difference in tumor invasiveness in cirrhotic patients with hepatocellular carcinoma fulfilling the Milan criteria treated by resection and transplantation: impact on long-term survival. Ann Surg 245:51–58
Bigourdan JM, Jaeck D, Meyer N et al (2003) Small hepatocellular carcinoma in Child A cirrhotic patients: hepatic resection versus transplantation. Liver Transpl 9:513–520
Duffy JP, Vardanian A, Benjamin E et al (2007) Liver transplantation criteria for hepatocellular carcinoma should be expanded: a 22-year experience with 467 patients at UCLA. Ann Surg 246:502–511
Forner A, Vilana R, Ayuso C et al (2008) Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatology 47:97–104
Louha M, Nicolet J, Zylberberg H et al (1999) Liver resection and needle liver biopsy cause hematogenous dissemination of liver cells. Hepatology 29:879–882
Stigliano R, Burroughs AK (2005) Should we biopsy each liver mass suspicious for HCC before liver transplantation?–no, please don’t. J Hepatol 43:563–568
Llovet JM, Fuster J, Bruix J (2004) The Barcelona approach: diagnosis, staging, and treatment of hepatocellular carcinoma. Liver Transpl 10(2 Suppl 1):S115–S120
Llovet JM, Di Bisceglie AM, Bruix J et al (2008) Design and endpoints of clinical trials in hepatocellular carcinoma. JNCI 100:698–711
Kaihara S, Kiuchi T, Ueda M et al (2003) Living-donor liver transplantation for hepatocellular carcinoma. Transplantation 75(3 Suppl):S37–S40
Ravaioli M, Grazi GL, Piscaglia F et al (2008) Liver transplantation for hepatocellular carcinoma: results of down-staging in patients initially outside the Milan selection criteria. Am J Transplant 8:2547–2557
Herrero JI, Sangro B, Quiroga J et al (2001) Influence of tumor characteristics on the outcome of liver transplantation among patients with liver cirrhosis and hepatocellular carcinoma. Liver Transpl 7:631–636
Yao FY, Kerlan RK, Jr, Hirose R et al (2008) Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis. Hepatology 48:819–827
Decaens T, Roudot-Thoraval F, Hadni-Bresson S et al (2006) Impact of UCSF criteria according to pre- and post-OLT tumor features: analysis of 479 patients listed for HCC with a short waiting time. Liver Transpl 12:1761–1769
Ravaioli M, Ercolani G, Cescon M et al (2004) Liver transplantation for hepatocellular carcinoma: further considerations on selection criteria. Liver Transpl 10:1195–1202
Yang SH, Suh KS, Lee HW et al (2007) A revised scoring system utilizing serum alphafetoprotein levels to expand candidates for living donor transplantation in hepatocellular carcinoma. Surgery 141:598–609
Marsh JW, Dvorchik I, Subotin M et al (1997) The prediction of risk of recurrence and time to recurrence of hepatocellular carcinoma after orthotopic liver transplantation: a pilot study. Hepatology 26:444–450
Schwartz M (2004) Liver transplantation for hepatocellular carcinoma. Gastroenterology 127(5 Suppl 1):S268–S276
Fisher RA, Maluf D, Cotterell AH et al (2004) Non-resective ablation therapy for hepatocellular carcinoma: effectiveness measured by intention-to-treat and dropout from liver transplant waiting list. Clin Transplant 18:502–512
Cillo U, Vitale A, Bassanello M et al (2004) Liver transplantation for the treatment of moderately or well-differentiated hepatocellular carcinoma. Ann Surg 239:150–159
Todo S, Furukawa H (2004) Living donor liver transplantation for adult patients with hepatocellular carcinoma: experience in Japan. Ann Surg 240:451–461
Yao FY, Bass NM, Nikolai B et al (2003) A follow-up analysis of the pattern and predictors of dropout from the waiting list for liver transplantation in patients with hepatocellular carcinoma: implications for the current organ allocation policy. Liver Transpl 9:684–692
Maddala YK, Stadheim L, Andrews JC et al (2004) Drop-out rates of patients with hepatocellular cancer listed for liver transplantation: outcome with chemoembolization. Liver Transpl 10:449–455
Porrett PM, Peterman H, Rosen M et al (2006) Lack of benefit of pre-transplant locoregional hepatic therapy for hepatocellular cancer in the current MELD era. Liver Transpl 12:665–673
Oldhafer KJ, Chavan A, Fruhauf NR et al (1998) Arterial chemoembolization before liver transplantation in patients with hepatocellular carcinoma: marked tumor necrosis, but no survival benefit? J Hepatol 29:953–959
Decaens T, Roudot-Thoraval F, Bresson-Hadni S et al (2005) Impact of pretransplantation transarterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma. Liver Transpl 11:767–775
Roayaie S, Frischer JS, Emre SH et al (2002) Long-term results with multimodal adjuvant therapy and liver transplantation for the treatment of hepatocellular carcinomas larger than 5 centimeters. Ann Surg 235:533–539
Graziadei IW, Sandmueller H, Waldenberger P et al (2003) Chemoembolization followed by liver transplantation for hepatocellular carcinoma impedes tumor progression while on the waiting list and leads to excellent outcome. Liver Transpl 9:557–563
Hayashi PH, Ludkowski M, Forman LM et al (2004) Hepatic artery chemoembolization for hepatocellular carcinoma in patients listed for liver transplantation. Am J Transpl 4:782–787
Varela M, Real MI, Burrel M et al (2007) Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol 46:474–481
Llovet JM, Bruix J (2003) Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 37:429–442
Lesurtel M, Mullhaupt B, Pestalozzi BC, Pfammatter T, Clavien PA (2006) Transarterial chemoembolization as a bridge to liver transplantation for hepatocellular carcinoma: an evidence-based analysis. Am J Transplant 6:2644–2650
Aloia TA, Fahy BN (2008) A decision analysis model predicts the optimal treatment pathway for patients with colorectal cancer and resectable synchronous liver metastases. Clin Colorectal Cancer 7:197–201
Lu DS, Yu NC, Raman SS et al (2005) Percutaneous radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation. Hepatology 41:1130–1137
Lu DS, Yu NC, Raman SS et al (2005) Radiofrequency ablation of hepatocellular carcinoma: treatment success as defined by histologic examination of the explanted liver. Radiology 234:954–960
Mazzaferro V, Battiston C, Perrone S et al (2004) Radiofrequency ablation of small hepatocellular carcinoma in cirrhotic patients awaiting liver transplantation: a prospective study. Ann Surg 240:900–909
Salem R, Thurston KG (2006) Radioembolization with yttrium-90 microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies: part 3: comprehensive literature review and future direction. J Vasc Interv Radiol 17:1571–1593
Kulik LM, Atassi B, van Holsbeeck L et al (2006) Yttrium-90 microspheres (TheraSphere) treatment of unresectable hepatocellular carcinoma: downstaging to resection, RFA and bridge to transplantation. J Surg Oncol 94:572–586
Riaz A, Kulik L, Lewandowski RJ et al (2009) Radiologic-pathologic correlation of hepatocellular carcinoma treated with internal radiation using yttrium-90 microspheres. Hepatology 49:1185–1193
Lo CM, Liu CL, Chan SC et al (2007) A randomized, controlled trial of postoperative adjuvant interferon therapy after resection of hepatocellular carcinoma. Ann Surg 245:831–842
Simonetti RG, Liberati A, Angiolini C, Pagliaro L (1997) Treatment of hepatocellular carcinoma: a systematic review of randomized controlled trials. Ann Oncol 8:117–136
Abou-Alfa GK, Schwartz L, Ricci S et al (2006) Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 24:4293–4300
Llovet JM, Ricci S, Mazzaferro V et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390
Llovet JM, Bruix J (2008) Molecular targeted therapies in hepatocellular carcinoma. Hepatology 48:1312–1327
Fernandez JA, Robles R, Marin C et al (2003) Can we expand the indications for liver transplantation among hepatocellular carcinoma patients with increased tumor size? Transplant Proc 35:1818–1820
Leung JY, Zhu AX, Gordon FD et al (2004) Liver transplantation outcomes for early-stage hepatocellular carcinoma: results of a multicenter study. Liver Transpl 10:1343–1354
Yao FY, Ferrell L, Bass NM, Bacchetti P, Ascher NL, Roberts JP (2002) Liver transplantation for hepatocellular carcinoma: comparison of the proposed UCSF criteria with the Milan criteria and the Pittsburgh modified TNM criteria. Liver Transpl 8:765–774
Mazzaferro V, Llovet JM, Miceli R et al (2009) Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol 10:35–43
Majno PE, Adam R, Bismuth H et al (1997) Influence of preoperative transarterial lipiodol chemoembolization on resection and transplantation for hepatocellular carcinoma in patients with cirrhosis. Ann Surg 226:688–701
Yao FY, Hirose R, LaBerge JM et al (2005) A prospective study on downstaging of hepatocellular carcinoma prior to liver transplantation. Liver Transpl 11:1505–1514
Llovet JM, Schwartz M, Fuster J, Bruix J (2006) Expanded criteria for hepatocellular carcinoma through down-staging prior to liver transplantation: not yet there. Semin Liver Dis 26:248–253
Belghiti J, Cortes A, Abdalla EK et al (2003) Resection prior to liver transplantation for hepatocellular carcinoma. Ann Surg 238:885–893
Fong Y, Sun RL, Jarnagin W, Blumgart LH (1999) An analysis of 412 cases of hepatocellular carcinoma at a Western center. Ann Surg 229:790–800
Ercolani G, Grazi GL, Ravaioli M et al (2003) Liver resection for hepatocellular carcinoma on cirrhosis: univariate and multivariate analysis of risk factors for intrahepatic recurrence. Ann Surg 237:536–543
Adam R, Azoulay D, Castaing D et al (2003) Liver resection as a bridge to transplantation for hepatocellular carcinoma on cirrhosis: a reasonable strategy? Ann Surg 238:508–519
Kulik L, Abecassis M (2004) Living donor liver transplantation for hepatocellular carcinoma. Gastroenterology 127(5 Suppl 1):S277–S282
Fisher RA, Kulik LM, Freise CE et al (2007) Hepatocellular carcinoma recurrence and death following living and deceased donor liver transplantation. Am J Transplant 7:1601–1608
Thuluvath PJ, Yoo HY (2004) Graft and patient survival after adult live donor liver transplantation compared to a matched cohort who received a deceased donor transplantation. Liver Transpl 10:1263–1238
Hwang S, Lee SG, Joh JW, Suh KS, Kim DG (2005) Liver transplantation for adult patients with hepatocellular carcinoma in Korea: comparison between cadaveric donor and living donor liver transplantations. Liver Transpl 11:1265–1272
Lo CM, Fan ST, Liu CL, Chan SC, Wong J (2004) The role and limitation of living donor liver transplantation for hepatocellular carcinoma. Liver Transpl 10:440–447
Sarasin FP, Majno PE, Llovet JM, Bruix J, Mentha G, Hadengue A (2001) Living donor liver transplantation for early hepatocellular carcinoma: A life-expectancy and cost-effectiveness perspective. Hepatology 33:1073–1079
Zavaglia C, De Carlis L, Alberti AB et al (2005) Predictors of long-term survival after liver transplantation for hepatocellular carcinoma. Am J Gastroenterol 100:2708–2716
Margarit C, Charco R, Hidalgo E, Allende H, Castells L, Bilbao I (2002) Liver transplantation for malignant diseases: selection and pattern of recurrence. World J Surg 26:257–263
Schlitt HJ, Neipp M, Weimann A et al (1999) Recurrence patterns of hepatocellular and fibrolamellar carcinoma after liver transplantation. J Clin Oncol 17:324–331
Shimoda M, Ghobrial RM, Carmody IC et al (2004) Predictors of survival after liver transplantation for hepatocellular carcinoma associated with Hepatitis C. Liver Transpl 10:1478–1486
Thuluvath PJ, Maheshwari A, Thuluvath NP, Nguyen GC, Segev DL (2009) Survival after liver transplantation for hepatocellular carcinoma in the model for end-stage liver disease and pre-model for end-stage liver disease eras and the independent impact of hepatitis C virus. Liver Transpl 15:754–762
Klintmalm GB (1998) Liver transplantation for hepatocellular carcinoma: a registry report of the impact of tumor characteristics on outcome. Ann Surg 228:479–490
Pawlik TM, Delman KA, Vauthey JN et al (2005) Tumor size predicts vascular invasion and histologic grade: Implications for selection of surgical treatment for hepatocellular carcinoma. Liver Transpl 11:1086–1092
Esnaola NF, Lauwers GY, Mirza NQ et al (2002) Predictors of microvascular invasion in patients with hepatocellular carcinoma who are candidates for orthotopic liver transplantation. J Gastrointest Surg 6:224–232
Busuttil RW, Farmer DG, Yersiz H et al (2005) Analysis of long-term outcomes of 3200 liver transplantations over two decades: a single-center experience. Ann Surg 241:905–918
Vivarelli M, Bellusci R, Cucchetti A et al (2002) Low recurrence rate of hepatocellular carcinoma after liver transplantation: better patient selection or lower immunosuppression? Transplantation 74:1746–1751
Vivarelli M, Cucchetti A, Piscaglia F et al (2005) Analysis of risk factors for tumor recurrence after liver transplantation for hepatocellular carcinoma: key role of immunosuppression. Liver Transpl 11:497–503
Guba M, von Breitenbuch P, Steinbauer M et al (2002) Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat Med 8:128–135
Aloia TA, Goss JA (2009) A report of outcomes after orthotopic liver transplant with allografts from heparin antibody-positive donors. Exp Clin Transplant 7:13–17
Guba M, Steinbauer M, Ruhland V et al (2002) Elevated MIA serum levels are predictors of poor prognosis after surgical resection of metastatic malignant melanoma. Oncol Reports 9:981–984
Schumacher G, Oidtmann M, Rosewicz S et al (2002) Sirolimus inhibits growth of human hepatoma cells in contrast to tacrolimus which promotes cell growth. Transplant Proc 34:1392–1393
Kneteman NM, Oberholzer J, Al Saghier M et al (2004) Sirolimus-based immunosuppression for liver transplantation in the presence of extended criteria for hepatocellular carcinoma. Liver Transpl 10:1301–1311
Marsh JW, Finkelstein SD, Demetris AJ et al (2003) Genotyping of hepatocellular carcinoma in liver transplant recipients adds predictive power for determining recurrence-free survival. Liver Transpl 9:664–671
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Aloia, T.A., Gaber, A.O., Ghobrial, R.M. (2011). Liver Transplant for Hepatocellular Carcinoma. In: McMasters, K. (eds) Hepatocellular Carcinoma:. Springer, New York, NY. https://doi.org/10.1007/978-1-60327-522-4_14
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