Journal of Cancer Research and Clinical Oncology

, Volume 135, Issue 10, pp 1403–1412

Liver transplantation outcomes in 1,078 hepatocellular carcinoma patients: a multi-center experience in Shanghai, China

  • Jia Fan
  • Guang-Shun Yang
  • Zhi-Ren Fu
  • Zhi-Hai Peng
  • Qiang Xia
  • Chen-Hong Peng
  • Jian-Ming Qian
  • Jian Zhou
  • Yang Xu
  • Shuang-Jian Qiu
  • Lin Zhong
  • Guang-Wen Zhou
  • Jian-Jun Zhang
Original Paper



To evaluate current selection criteria for patients undergoing liver transplantation (LT) in response to hepatocellular carcinoma (HCC), and to analyze the prognostic factors for successful transplantation.


We evaluated the outcome of 1,078 consecutive patients with HCC from the Shanghai Multi-Center Collaborative LT Group who underwent LT over a 6-year period. Clinicopathologic data for these patients were evaluated. The prognostic significance was assessed using Kaplan–Meier survival estimates and log-rank tests. Multivariate study with Cox’s proportional hazard model was used to evaluate the prognosis-relative aspects.


We determined that expansion of Milan criteria to include: a solitary lesion ≤9 cm in diameter, no more than three lesions with the largest ≤5 cm, a total tumor diameter ≤9 cm without macrovascular invasion, lymph node invasion and extrahepatic metastasis (referred to as the “Shanghai criteria”), resulted in overall survival (OS) and disease-free survival (DFS) rates that were similar to the Milan criteria. Multivariate analysis using the Cox proportional hazards regression model showed that the Child-Pugh-Turcotte classification (P = 0.010, 0.000), tumor differentiation (P = 0.001, 0.000), tumor size (P = 0.000, 0.000) and number (P = 0.014, 0.016), macrovascular invasion (P = 0.022, 0.000) and alpha-fetoprotein (AFP) levels (P = 0.031, 0.003) were independent predictors of OS and DFS, while post-LT chemotherapy (OS, P = 0.000) and tumor encapsulation (DFS, P = 0.038) were independent predictors of OS or DFS.


Shanghai criteria expanded the current criteria while maintaining similar survival.


Hepatocellular carcinoma Liver transplantation Criteria Prognosis 



Hepatocellular carcinoma


Liver transplantation






Computed tomography


Magnetic resonance imaging


World Health Organization


Mycophenolate mofetil




Transcatheter arterial chemoembolization


Percutaneous ethanol injection


Radio-frequency ablation


Overall survival


Disease-free survival






International Union against cancer


Hepatitis B virus


Hepatitis B surface antigen


Hepatitis C virus


Positron emission tomography


  1. Bismuth H, Majno PE, Adam R (1999) Liver transplantation for hepatocellular carcinoma. Semin Liver Dis 19:311–322. doi:10.1055/s-2007-1007120 CrossRefPubMedGoogle Scholar
  2. Chen G, Lin W, Shen F, Iloeje UH, London WT, Evans AA (2006) Past HBV viral load as predictor of mortality and morbidity from HCC and chronic liver disease in a prospective study. Am J Gastroenterol 101:1797–1803. doi:10.1111/j.1572-0241.2006.00647.x CrossRefPubMedGoogle Scholar
  3. De Carlis L, Giacomoni A, Lauterio A, Slim A, Sammartino C, Pirotta V, Colella G, Forti D (2003) Liver transplantation for hepatocellular cancer: should the current indication criteria be changed? Transpl Int 16:115–122. doi:10.1111/j.1432-2277.2003.tb00272.x CrossRefPubMedGoogle Scholar
  4. de Villa V, Lo CM (2007) Liver transplantation for hepatocellular carcinoma in Asia. Oncologist 12:1321–1331. doi:10.1634/theoncologist.12-11-1321 CrossRefPubMedGoogle Scholar
  5. Debruyne EN, Delanghe JR (2008) Diagnosing and monitoring hepatocellular carcinoma with alpha-fetoprotein: new aspects and applications. Clin Chim Acta 395:19–26. doi:10.1016/j.cca.2008.05.010 CrossRefPubMedGoogle Scholar
  6. Di Benedetto F, Di Sandro S, De Ruvo N, Masetti M, Montalti R, Romano A, Guerrini GP, Ballarin R, De Blasiis MG, Gerunda GE (2007) Sirolimus monotherapy in liver transplantation. Transplant Proc 39:1930–1932. doi:10.1016/j.transproceed.2007.07.018 CrossRefPubMedGoogle Scholar
  7. Duffy JP, Vardanian A, Benjamin E, Watson M, Farmer DG, Ghobrial RM, Lipshutz G, Yersiz H, Lu DS, Lassman C, Tong MJ, Hiatt JR, Busuttil RW (2007) Liver transplantation criteria for hepatocellular carcinoma should be expanded: a 22-year experience with 467 patients at UCLA. Ann Surg 246:502–509. doi:10.1097/SLA.0b013e318148c704 (discussion 509-11)CrossRefPubMedGoogle Scholar
  8. Fan J, Zhou J, Xu Y, Qiu SJ, Wu ZQ, Yu Y, Huang XW, Tang ZY, Wang YQ (2006) Indication of liver transplantation for hepatocellular carcinoma: Shanghai Fudan Criteria. Zhonghua Yi Xue Za Zhi 86:1227–1231PubMedGoogle Scholar
  9. Hertl M, Cosimi AB (2005) Liver transplantation for malignancy. Oncologist 10:269–281. doi:10.1634/theoncologist.10-4-269 CrossRefPubMedGoogle Scholar
  10. Huang J (2007) Ethical and legislative perspectives on liver transplantation in the People’s Republic of China. Liver Transpl 13:193–196. doi:10.1002/lt.21081 CrossRefPubMedGoogle Scholar
  11. Huang J, Mao Y, Millis JM (2008) Government policy and organ transplantation in China. Lancet 372:1937–1938. doi:10.1016/S0140-6736(08)61359-8 CrossRefPubMedGoogle Scholar
  12. Marubashi S, Dono K, Nagano H, Sugita Y, Asaoka T, Hama N, Miyamoto A, Takeda Y, Umeshita K, Monden M (2007) Detection of AFP mRNA-expressing cells in the peripheral blood for prediction of HCC recurrence after living donor liver transplantation. Transpl Int 20:576–582. doi:10.1111/j.1432-2277.2007.00480.x CrossRefPubMedGoogle Scholar
  13. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L (1996) Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334:693–699. doi:10.1056/NEJM199603143341104 CrossRefPubMedGoogle Scholar
  14. Mazzaferro V, Chun YS, Poon RT, Schwartz ME, Yao FY, Marsh JW, Bhoori S, Lee SG (2008) Liver Transplantation for Hepatocellular Carcinoma. Ann Surg Oncol 15:1001–1007. doi:10.1245/s10434-007-9559-5 CrossRefPubMedGoogle Scholar
  15. Mourad W, Khalaf H, Tulbah A, Al Omari M, Al Mana H, Neimatallah M (2007) Clinicopathologic features of hepatic neoplasms in explanted livers: a single institution experience. Ann Saudi Med 27:437–441CrossRefPubMedGoogle Scholar
  16. Onaca N, Davis GL, Goldstein RM, Jennings LW, Klintmalm GB (2007) Expanded criteria for liver transplantation in patients with hepatocellular carcinoma: a report from the International Registry of Hepatic Tumors in Liver Transplantation. Liver Transpl 13:391–399. doi:10.1002/lt.21095 CrossRefPubMedGoogle Scholar
  17. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108. doi:10.3322/canjclin.55.2.74 CrossRefPubMedGoogle Scholar
  18. Perez-Saborido B, de los Galanes SJ, Meneu-Diaz JC, Romero CJ, Elola-Olaso AM, Suarez YF, Valencia VB, Moreno-Gonzalez E (2007) Tumor recurrence after liver transplantation for hepatocellular carcinoma: recurrence pathway and prognostic factors. Transplant Proc 39:2304–2307. doi:10.1016/j.transproceed.2007.06.059 CrossRefPubMedGoogle Scholar
  19. Rakela J, Fung JJ (2007) Liver transplantation in China. Liver Transpl 13:182. doi:10.1002/lt.21079 CrossRefPubMedGoogle Scholar
  20. Rossi M, Merli M, Lai Q, Gentili F, Mennini G, Bussotti A, Pugliese F, Della Pietra F, Poli L, Novelli G, Giusto M, Ginanni Corradini S, Iappelli M, Onetti Muda A, Di Tondo U, Gossetti F, Attili AF, Berloco PB (2007) Outcome after liver transplantation in patients with cirrhosis and hepatocellular carcinoma. Transplant Proc 39:1895–1897. doi:10.1016/j.transproceed.2007.05.083 CrossRefPubMedGoogle Scholar
  21. Said A, Einstein M, Lucey MR (2007) Liver transplantation: an update 2007. Curr Opin Gastroenterol 23:292–298. doi:10.1097/MOG.0b013e3280f9df41 CrossRefPubMedGoogle Scholar
  22. Schwartz ME, Sung M, Mor E, Fisher A, Popescu I, Fiel I, Sheiner P, Emre S, Guy S, Miller CM (1995) A multidisciplinary approach to hepatocellular carcinoma in patients with cirrhosis. J Am Coll Surg 180:596–603PubMedGoogle Scholar
  23. Shi J, Zhu L, Liu S, Xie WF (2005) A meta-analysis of case-control studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma in China. Br J Cancer 92:607–612. doi:10.1038/sj.bjc.6602460 CrossRefPubMedGoogle Scholar
  24. Soejima Y, Taketomi A, Yoshizumi T, Uchiyama H, Aishima S, Terashi T, Shimada M, Maehara Y (2007) Extended indication for living donor liver transplantation in patients with hepatocellular carcinoma. Transplantation 83:893–899. doi:10.1097/ CrossRefPubMedGoogle Scholar
  25. Tang ZY (2001) Hepatocellular carcinoma—cause, treatment and metastasis. World J Gastroenterol 7:445–454PubMedGoogle Scholar
  26. Tang ZY, Ye SL, Liu YK, Qin LX, Sun HC, Ye QH, Wang L, Zhou J, Qiu SJ, Li Y, Ji XN, Liu H, Xia JL, Wu ZQ, Fan J, Ma ZC, Zhou XD, Lin ZY, Liu KD (2004) A decade’s studies on metastasis of hepatocellular carcinoma. J Cancer Res Clin Oncol 130:187–196. doi:10.1007/s00432-003-0511-1 CrossRefPubMedGoogle Scholar
  27. Todo S, Furukawa H, Tada M (2007) Extending indication: role of living donor liver transplantation for hepatocellular carcinoma. Liver Transpl 13:S48–S54. doi:10.1002/lt.21334 CrossRefPubMedGoogle Scholar
  28. Vitale A, Gringeri E, Valmasoni M, D’Amico F, Carraro A, Pauletto A, D’Amico FJ, Polacco M, D’Amico DF, Cillo U (2007) Long-term results of liver transplantation for hepatocellular carcinoma: an update of the University of Padova experience. Transplant Proc 39:1892–1894. doi:10.1016/j.transproceed.2007.05.031 CrossRefPubMedGoogle Scholar
  29. Vivarelli M, Cucchetti A, Piscaglia F, La Barba G, Bolondi L, Cavallari A, Pinna AD (2005) Analysis of risk factors for tumor recurrence after liver transplantation for hepatocellular carcinoma: key role of immunosuppression. Liver Transpl 11:497–503. doi:10.1002/lt.20391 CrossRefPubMedGoogle Scholar
  30. Wittekind C (2006) Pitfalls in the classification of liver tumors. Pathologe 27:289–293. doi:10.1007/s00292-006-0834-1 CrossRefPubMedGoogle Scholar
  31. Wittekind C, International Union Against Cancer (2005) TNM atlas : illustrated guide to the TNM/pTNM classification of malignant tumours. Springer, BerlinGoogle Scholar
  32. Yao FY (2007) Expanded criteria for liver transplantation in patients with hepatocellular carcinoma. Hepatol Res 37(Suppl 2):S267–S274. doi:10.1111/j.1872-034X.2007.00195.x CrossRefPubMedGoogle Scholar
  33. Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, Ascher NL, Roberts JP (2001) Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 33:1394–1403. doi:10.1053/jhep.2001.24563 CrossRefPubMedGoogle Scholar
  34. 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. doi:10.1053/jlts.2002.34892 CrossRefPubMedGoogle Scholar
  35. Yao FY, Xiao L, Bass NM, Kerlan R, Ascher NL, Roberts JP (2007) Liver transplantation for hepatocellular carcinoma: validation of the UCSF-expanded criteria based on preoperative imaging. Am J Transplant 7:2587–2596. doi:10.1111/j.1600-6143.2007.01965.x CrossRefPubMedGoogle Scholar
  36. Zheng SS, Xu X, Wu J, Chen J, Wang WL, Zhang M, Liang TB, Wu LM (2008) Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation 85:1726–1732. doi:10.1097/TP.0b013e31816b67e4 CrossRefPubMedGoogle Scholar
  37. Zhou J, Fan J, Wang Z, Wu ZQ, Qiu SJ, Huang XW, Yu Y, Sun J, Xiao YS, He YF, Wang YQ, Tang ZY (2006) Conversion to sirolimus immunosuppression in liver transplantation recipients with hepatocellular carcinoma: Report of an initial experience. World J Gastroenterol 12:3114–3118PubMedGoogle Scholar
  38. Zieniewicz K, Patkowski W, Nyckowski P, Alsharabi A, Michalowicz B, Pawlak J, Paluszkiewicz R, Wroblewski T, Najnigier B, Smoter P, Hevelke P, Skwarek A, Remiszewski P, Kotulski M, Skalski M, Paczek L, Krawczyk M (2007) Results of liver transplantation for hepatocellular cancer. Ann Transplant 12:11–14PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Jia Fan
    • 1
  • Guang-Shun Yang
    • 2
  • Zhi-Ren Fu
    • 3
  • Zhi-Hai Peng
    • 4
  • Qiang Xia
    • 5
  • Chen-Hong Peng
    • 6
  • Jian-Ming Qian
    • 7
  • Jian Zhou
    • 1
  • Yang Xu
    • 1
  • Shuang-Jian Qiu
    • 1
  • Lin Zhong
    • 4
  • Guang-Wen Zhou
    • 6
  • Jian-Jun Zhang
    • 5
  1. 1.Liver Cancer Institute, Shanghai Medical School, Zhong Shan HospitalFudan UniversityShanghaiPeople’s Republic of China
  2. 2.Dong Fang Gan Dan HospitalShanghai Second Military Medical UniversityShanghaiPeople’s Republic of China
  3. 3.Chang Zheng HospitalShanghai Second Military Medical UniversityShanghaiPeople’s Republic of China
  4. 4.Shanghai First HospitalMedical School of Jiaotong UniversityShanghaiPeople’s Republic of China
  5. 5.Ren Ji HospitalMedical School of Jiaotong UniversityShanghaiPeople’s Republic of China
  6. 6.Rui Jing HospitalMedical School of Jiaotong UniversityShanghaiPeople’s Republic of China
  7. 7.Hua Shan Hospital, Shanghai Medical SchoolFudan UniversityShanghaiPeople’s Republic of China

Personalised recommendations