Journal of Gastrointestinal Surgery

, Volume 18, Issue 4, pp 701–708 | Cite as

The Postresection Alpha-Fetoprotein in Cirrhotic Patients with Hepatocellular Carcinoma. An Independent Predictor of Outcome

  • Marc-Antoine Allard
  • Antonio Sa Cunha
  • Aldrick Ruiz
  • Eric Vibert
  • Mylène Sebagh
  • Denis Castaing
  • René Adam
Original Article



The postresection alpha-fetoprotein (AFP) in cirrhotic patients with hepatocellular carcinoma (HCC) may predict overall survival (OS) and recurrence beyond Milan criteria (MC) among the subgroup of initially transplantable patients.


All patients with cirrhosis resected for HCC between January 1990 and December 2010 in a single institution and presenting a serum AFP value > 15 ng/ml at diagnosis were included. The postresection AFP was analyzed as a dichotomized variable: normalization (norm + group) or not (norm − group) within the 90-day postresection period.


Among 271 resected patients, 141 patients (52 %) had a level of serum AFP ≥ 15 ng/ml at diagnosis. Five-year OS and median survival were 42 % and 52 months in group norm + versus 20 % and 23 months in the group norm − (P = 0.009). On multivariate analysis, the absence of AFP normalization was an independent factor of poor OS as well as microvascular invasion, and satellites nodules. Among theoretically transplantable patients, independent predictors of recurrence beyond MC were the absence of AFP normalization (risk ratio (RR) 5.02 [1.53–16.34]) and microvascular invasion (RR 4.76 [1.42–15.34]).


The postresection AFP has an independent prognostic value. Transplantable patients resected for HCC without 90-day AFP normalization should be discussed for early liver transplantation.


Postresection alpha-fetoprotein Hepatocellular carcinoma Cirrhosis Milan criteria Liver transplantation 


  1. 1.
    Altekruse SF, McGlynn KA, Reichman ME: Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol 2009, 27:1485-1491.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Choti MA: Transplantation versus resection for hepatocellular carcinoma in the mild cirrhotic: framing the debate. J Gastrointest Surg 2009, 13:1021-1022.PubMedCrossRefGoogle Scholar
  3. 3.
    Cormier JN, Thomas KT, Chari RS, Pinson CW: Management of hepatocellular carcinoma. J Gastrointest Surg 2006, 10:761-780.PubMedCrossRefGoogle Scholar
  4. 4.
    Rahman A, Assifi MM, Pedroso FE, Maley WR, Sola JE, Lavu H, Winter JM, Yeo CJ, Koniaris LG: Is resection equivalent to transplantation for early cirrhotic patients with hepatocellular carcinoma? A meta-analysis. J Gastrointest Surg 2012, 16:1897-1909.PubMedCrossRefGoogle Scholar
  5. 5.
    Ng KK, Lo CM, Liu CL, Poon RT, Chan SC, Fan ST: Survival analysis of patients with transplantable recurrent hepatocellular carcinoma: implications for salvage liver transplant. Arch Surg 2008, 143:68-74; discussion 74.PubMedCrossRefGoogle Scholar
  6. 6.
    Majno PE, Sarasin FP, Mentha G, Hadengue A: Primary liver resection and salvage transplantation or primary liver transplantation in patients with single, small hepatocellular carcinoma and preserved liver function: an outcome-oriented decision analysis. Hepatology 2000, 31:899-906.PubMedCrossRefGoogle Scholar
  7. 7.
    Del Gaudio M, Ercolani G, Ravaioli M, Cescon M, Lauro A, Vivarelli M, Zanello M, Cucchetti A, Vetrone G, Tuci F, et al: Liver transplantation for recurrent hepatocellular carcinoma on cirrhosis after liver resection: University of Bologna experience. Am J Transplant 2008, 8:1177-1185.PubMedCrossRefGoogle Scholar
  8. 8.
    Cherqui D, Laurent A, Mocellin N, Tayar C, Luciani A, Van Nhieu JT, Decaens T, Hurtova M, Memeo R, Mallat A, Duvoux C: Liver resection for transplantable hepatocellular carcinoma: long-term survival and role of secondary liver transplantation. Ann Surg 2009, 250:738-746.PubMedCrossRefGoogle Scholar
  9. 9.
    Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L: Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996, 334:693-699.PubMedCrossRefGoogle Scholar
  10. 10.
    Abelev GI, Perova SD, Khramkova NI, Postnikova ZA, Irlin IS: Production of embryonal alpha-globulin by transplantable mouse hepatomas. Transplantation 1963, 1:174-180.PubMedCrossRefGoogle Scholar
  11. 11.
    Riaz A, Ryu RK, Kulik LM, Mulcahy MF, Lewandowski RJ, Minocha J, Ibrahim SM, Sato KT, Baker T, Miller FH, et al: Alpha-fetoprotein response after locoregional therapy for hepatocellular carcinoma: oncologic marker of radiologic response, progression, and survival. J Clin Oncol 2009, 27:5734-5742.PubMedCrossRefGoogle Scholar
  12. 12.
    Chan SL, Mo FK, Johnson PJ, Hui EP, Ma BB, Ho WM, Lam KC, Chan AT, Mok TS, Yeo W: New utility of an old marker: serial alpha-fetoprotein measurement in predicting radiologic response and survival of patients with hepatocellular carcinoma undergoing systemic chemotherapy. J Clin Oncol 2009, 27:446-452.PubMedCrossRefGoogle Scholar
  13. 13.
    Marrero JA, Feng Z, Wang Y, Nguyen MH, Befeler AS, Roberts LR, Reddy KR, Harnois D, Llovet JM, Normolle D, et al: Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma. Gastroenterology 2009, 137:110-118.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Mailey B, Artinyan A, Khalili J, Denitz J, Sanchez-Luege N, Sun CL, Bhatia S, Nissen N, Colquhoun SD, Kim J: Evaluation of absolute serum alpha-fetoprotein levels in liver transplant for hepatocellular cancer. Arch Surg 2011, 146:26-33.PubMedCrossRefGoogle Scholar
  15. 15.
    Vauthey JN, Pawlik TM, Abdalla EK, Arens JF, Nemr RA, Wei SH, Kennamer DL, Ellis LM, Curley SA: Is extended hepatectomy for hepatobiliary malignancy justified? Ann Surg 2004, 239:722-730; discussion 730-722.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Vauthey JN, Pawlik TM, Ribero D, Wu TT, Zorzi D, Hoff PM, Xiong HQ, Eng C, Lauwers GY, Mino-Kenudson M, et al: Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol 2006, 24:2065-2072.PubMedCrossRefGoogle Scholar
  17. 17.
    Vibert E, Azoulay D, Hoti E, Iacopinelli S, Samuel D, Salloum C, Lemoine A, Bismuth H, Castaing D, Adam R: Progression of alphafetoprotein before liver transplantation for hepatocellular carcinoma in cirrhotic patients: a critical factor. Am J Transplant 2010, 10:129-137.PubMedCrossRefGoogle Scholar
  18. 18.
    Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E, Pagliaro L, Colombo M, Rodes J: Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001, 35:421-430.PubMedCrossRefGoogle Scholar
  19. 19.
    Majno PE, Adam R, Bismuth H, Castaing D, Ariche A, Krissat J, Perrin H, Azoulay D: Influence of preoperative transarterial lipiodol chemoembolization on resection and transplantation for hepatocellular carcinoma in patients with cirrhosis. Ann Surg 1997, 226:688-701; discussion 701-683.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Ishizawa T, Hasegawa K, Aoki T, Takahashi M, Inoue Y, Sano K, Imamura H, Sugawara Y, Kokudo N, Makuuchi M: Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma. Gastroenterology 2008, 134:1908-1916.PubMedCrossRefGoogle Scholar
  21. 21.
    Bismuth H, Houssin D, Ornowski J, Meriggi F: Liver resections in cirrhotic patients: a Western experience. World J Surg 1986, 10:311-317.PubMedCrossRefGoogle Scholar
  22. 22.
    Tung-Ping Poon R, Fan ST, Wong J: Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg 2000, 232:10-24.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Sumie S, Kuromatsu R, Okuda K, Ando E, Takata A, Fukushima N, Watanabe Y, Kojiro M, Sata M: Microvascular invasion in patients with hepatocellular carcinoma and its predictable clinicopathological factors. Ann Surg Oncol 2008, 15:1375-1382.PubMedCrossRefGoogle Scholar
  24. 24.
    Toyoda H, Kumada T, Kaneoka Y, Osaki Y, Kimura T, Arimoto A, Oka H, Yamazaki O, Manabe T, Urano F, et al: Prognostic value of pretreatment levels of tumor markers for hepatocellular carcinoma on survival after curative treatment of patients with HCC. J Hepatol 2008, 49:223-232.PubMedCrossRefGoogle Scholar
  25. 25.
    Johnson PJ: The role of serum alpha-fetoprotein estimation in the diagnosis and management of hepatocellular carcinoma. Clin Liver Dis 2001, 5:145-159.PubMedCrossRefGoogle Scholar
  26. 26.
    Peng SY, Chen WJ, Lai PL, Jeng YM, Sheu JC, Hsu HC: High alpha-fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: significance of hepatitis virus infection, age, p53 and beta-catenin mutations. Int J Cancer 2004, 112:44-50.PubMedCrossRefGoogle Scholar
  27. 27.
    Yamamoto K, Imamura H, Matsuyama Y, Hasegawa K, Beck Y, Sugawara Y, Makuuchi M, Kokudo N: Significance of alpha-fetoprotein and des-gamma-carboxy prothrombin in patients with hepatocellular carcinoma undergoing hepatectomy. Ann Surg Oncol 2009, 16:2795-2804.PubMedCrossRefGoogle Scholar
  28. 28.
    Santambrogio R, Opocher E, Costa M, Barabino M, Zuin M, Bertolini E, De Filippi F, Bruno S: Hepatic resection for “BCLC stage A” hepatocellular carcinoma. The prognostic role of alpha-fetoprotein. Ann Surg Oncol 2012, 19:426-434.PubMedCrossRefGoogle Scholar
  29. 29.
    Lee YH, Hsu CY, Huang YH, Su CW, Lin HC, Hsia CY, Huo TI: alpha-fetoprotein-to-total tumor volume ratio predicts post-operative tumor recurrence in hepatocellular carcinoma. J Gastrointest Surg 2013, 17:730-738.PubMedCrossRefGoogle Scholar
  30. 30.
    Zimmerman MA, Ghobrial RM, Tong MJ, Hiatt JR, Cameron AM, Hong J, Busuttil RW: Recurrence of hepatocellular carcinoma following liver transplantation: a review of preoperative and postoperative prognostic indicators. Arch Surg 2008, 143:182-188; discussion 188.PubMedCrossRefGoogle Scholar
  31. 31.
    Duvoux C, Roudot-Thoraval F, Decaens T, Pessione F, Badran H, Wolf P, Francoz C, Compagnon P, Vanlemmens C, Dumortier J, et al: Liver transplantation for hepatocellular carcinoma: a model including alpha-fetoprotein improves the performance of Milan criteria. Gastroenterology 2012.Google Scholar
  32. 32.
    Nobuoka D, Kato Y, Gotohda N, Takahashi S, Nakagohri T, Konishi M, Kinoshita T, Nakatsura T: Postoperative serum alpha-fetoprotein level is a useful predictor of recurrence after hepatectomy for hepatocellular carcinoma. Oncol Rep 2010, 24:521-528.PubMedGoogle Scholar
  33. 33.
    Nanashima A, Taura N, Abo T, Ichikawa T, Sakamoto I, Nagayasu T, Nakao K: Tumor marker levels before and after curative treatment of hepatocellular carcinoma as predictors of patient survival. Dig Dis Sci 2011, 56:3086-3100.PubMedCrossRefGoogle Scholar
  34. 34.
    Shim JH, Han S, Lee YJ, Lee SG, Kim KM, Lim YS, Chung YH, Lee YS, Lee HC: Half-Life of Serum Alpha-Fetoprotein: An Early Prognostic Index of Recurrence and Survival After Hepatic Resection for Hepatocellular Carcinoma. Ann Surg 2012.Google Scholar
  35. 35.
    Seppala M, Ruoslahti E: Radioimmunoassay of maternal serum alpha fetoprotein during pregnancy and delivery. Am J Obstet Gynecol 1972, 112:208-212.PubMedGoogle Scholar
  36. 36.
    Sakon M, Nagano H, Nakamori S, Dono K, Umeshita K, Murakami T, Nakamura H, Monden M: Intrahepatic recurrences of hepatocellular carcinoma after hepatectomy: analysis based on tumor hemodynamics. Arch Surg 2002, 137:94-99.PubMedCrossRefGoogle Scholar
  37. 37.
    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, 55:132-140.PubMedCrossRefGoogle Scholar
  38. 38.
    Tincani G, Hoti E, Andreani P, Ricca L, Pittau G, Vitale V, Blandin F, Adam R, Castaing D, Azoulay D: Operative risks of domino liver transplantation for the familial amyloid polyneuropathy liver donor and recipient: a double analysis. Am J Transplant 2011, 11:759-766.PubMedCrossRefGoogle Scholar

Copyright information

© The Society for Surgery of the Alimentary Tract 2014

Authors and Affiliations

  • Marc-Antoine Allard
    • 1
    • 4
  • Antonio Sa Cunha
    • 1
    • 2
    • 4
  • Aldrick Ruiz
    • 1
    • 4
  • Eric Vibert
    • 1
    • 2
    • 4
  • Mylène Sebagh
    • 1
    • 4
    • 5
  • Denis Castaing
    • 1
    • 2
    • 4
  • René Adam
    • 1
    • 3
    • 4
  1. 1.Centre Hépato-BiliaireAP-HP, Hôpital Paul BrousseVillejuifFrance
  2. 2.InsermVillejuifFrance
  3. 3.InsermVillejuifFrance
  4. 4.Université Paris-SudVillejuifFrance
  5. 5.Department of PathologyAP-HP, Hôpital du Kremlin-BicêtreKremlin-BicêtreFrance

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