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Infection with Hepatitis C Virus is an Adverse Prognostic Factor after Liver Resection for Early-stage Hepatocellular Carcinoma

Implications for the Management of Hepatocellular Carcinoma Eligible for Liver Transplantation

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Introduction

Recent data support liver resection (LR) as first-line approach in patients with preserved liver function who have resectable/transplantable hepatocellular carcinoma (HCC). This study was designed to evaluate the outcome of LR in patients with transplantable HCC.

Methods

Between 1998 and 2009, 75 patients (65 men, mean age 61 ± 11 years) with HCC eligible for liver transplantation (LT) underwent LR. The underlying hepatic disease was related to hepatitis C (HCV) in 30 (40 %) patients, hepatitis B (HBV) in 15 (20 %) patients, alcohol abuse in 26 patients (36 %) and other in 10 patients (13 %). Fifty-five (73 %) patients had cirrhosis. Intermittent clamping of the hepatic pedicle was used in 41 (55 %) patients. Treatment of recurrence by salvage LT was performed in 6 (8 %) patients.

Results

Operative morbidity and mortality rates were 37 and 5  % respectively. At 1, 3, and 5 years, overall (OS) and disease-free (DFS) survival rates were 81, 69,55 and 56, 31, and 21 %, respectively. On multivariate analysis, HCV infection was the only independent factor associated with decreased OS (p = 0.02). On multivariate analysis, HCV infection (p = 0.05) and intermittent hepatic pedicle clamping (p = 0.003) were associated with decreased DFS. The 1-, 3-, and 5-year OS and DFS rates in patients with HCV-related HCC were 69, 53, 38 and 50, 18, and 9% respectively.

Conclusions

Overall and disease-free survival after liver resection in patients with HCV-related HCC and preserved liver function is poor. Primary LT should be offered to these patients.

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References

  1. Koniaris LG, Levi DM, Pedroso FE, Franceschi D, Tzakis AG, Santamaria-Barria JA, Tang J, Anderson M, Misra S, Solomon NL, Jin X, DiPasco PJ, Byrne MM, Zimmers TA. Is surgical resection superior to transplantation in the treatment of hepatocellular carcinoma? Ann Surg. 2011;254(3):527–37. discussion 537-8.

    Article  PubMed  Google Scholar 

  2. Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020–2.

    Article  PubMed  Google Scholar 

  3. 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(5):738–46.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  5. Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology. 1999;30(6):1434–40.

    Article  PubMed  CAS  Google Scholar 

  6. Ioannou GN, Perkins JD, Carithers RL Jr. Liver transplantation for hepatocellular carcinoma: impact of the MELD allocation system and predictors of survival. Gastroenterology. 2008;134(5):1342–51.

    Article  PubMed  Google Scholar 

  7. Del Gaudio M, Ercolani G, Ravaioli M, Cescon M, Lauro A, Vivarelli M, Zanello M, Cucchetti A, Vetrone G, Tuci F, Ramacciato G, Grazi GL, Pinna AD. Liver transplantation for recurrent hepatocellular carcinoma on cirrhosis after liver resection: University of Bologna experience. Am J Transplant. 2008;8(6):1177–85.

    Article  PubMed  Google Scholar 

  8. Margarit C, Escartin A, Castells L, Vargas V, Allende E, Bilbao I. Resection for hepatocellular carcinoma is a good option in Child-Turcotte-Pugh class A patients with cirrhosis who are eligible for liver transplantation. Liver Transpl. 2005;11(10):1242–51.

    Article  PubMed  Google Scholar 

  9. Berry K, Ioannou GN. Are patients with Child’s A cirrhosis and hepatocellular carcinoma appropriate candidates for liver transplantation? Am J Transplant. 2012;12(3):706–17.

    Article  PubMed  CAS  Google Scholar 

  10. 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(4):899–906.

    Article  PubMed  CAS  Google Scholar 

  11. Poon RT, Fan ST, Lo CM, Liu CL, Wong J. Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation. Ann Surg. 2002;235(3):373–82.

    Article  PubMed  Google Scholar 

  12. Sala M, Fuster J, Llovet JM, Navasa M, Sole M, Varela M, Pons F, Rimola A, Garcia-Valdecasas JC, Bru C, Bruix J. High pathological risk of recurrence after surgical resection for hepatocellular carcinoma: an indication for salvage liver transplantation. Liver Transpl. 2004;10(10):1294–300.

    Article  PubMed  Google Scholar 

  13. 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(11):693–9.

    Article  PubMed  CAS  Google Scholar 

  14. Cucchetti A, Ercolani G, Vivarelli M, Cescon M, Ravaioli M, Ramacciato G, Grazi GL, Pinna AD. Is portal hypertension a contraindication to hepatic resection? Ann Surg. 2009;250(6):922–8.

    Article  PubMed  Google Scholar 

  15. Wakai T, Shirai Y, Sakata J, Kaneko K, Cruz PV, Akazawa K, Hatakeyama K. Anatomic resection independently improves long-term survival in patients with T1-T2 hepatocellular carcinoma. Ann Surg Oncol. 2007;14(4):1356–65.

    Article  PubMed  Google Scholar 

  16. Regimbeau JM, Kianmanesh R, Farges O, Dondero F, Sauvanet A, Belghiti J. Extent of liver resection influences the outcome in patients with cirrhosis and small hepatocellular carcinoma. Surgery. 2002;131(3):311–7.

    Article  PubMed  Google Scholar 

  17. Hasegawa K, Kokudo N, Imamura H, Matsuyama Y, Aoki T, Minagawa M, Sano K, Sugawara Y, Takayama T, Makuuchi M. Prognostic impact of anatomic resection for hepatocellular carcinoma. Ann Surg. 2005;242(2):252–9.

    Article  PubMed  Google Scholar 

  18. Belghiti J, Cortes A, Abdalla EK, Regimbeau JM, Prakash K, Durand F, Sommacale D, Dondero F, Lesurtel M, Sauvanet A, Farges O, Kianmanesh R. Resection prior to liver transplantation for hepatocellular carcinoma. Ann Surg. 2003;238(6):885–92; discussion 892-3.

    Article  PubMed  Google Scholar 

  19. Minagawa M, Makuuchi M, Takayama T, Kokudo N. Selection criteria for repeat hepatectomy in patients with recurrent hepatocellular carcinoma. Ann Surg. 2003;238(5):703–10.

    Article  PubMed  Google Scholar 

  20. Poon RT, Fan ST, Lo CM, Liu CL, Wong J. Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors. Ann Surg. 1999;229(2):216–22.

    Article  PubMed  CAS  Google Scholar 

  21. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13.

    Article  PubMed  Google Scholar 

  22. Roayaie S, Haim MB, Emre S, Fishbein TM, Sheiner PA, Miller CM, Schwartz ME. Comparison of surgical outcomes for hepatocellular carcinoma in patients with hepatitis B versus hepatitis C: a western experience. Ann Surg Oncol. 2000;7(10):764–70.

    Article  PubMed  CAS  Google Scholar 

  23. Huang YH, Wu JC, Chen CH, Chang TT, Lee PC, Chau GY, Lui WY, Chang FY, Lee SD. Comparison of recurrence after hepatic resection in patients with hepatitis B vs. hepatitis C-related small hepatocellular carcinoma in hepatitis B virus endemic area. Liver Int. 2005;25(2):236–41.

    Article  PubMed  Google Scholar 

  24. Li Q, Li H, Qin Y, Wang PP, Hao X. Comparison of surgical outcomes for small hepatocellular carcinoma in patients with hepatitis B versus hepatitis C: a Chinese experience. J Gastroenterol Hepatol. 2007;22(11):1936–41.

    Article  PubMed  Google Scholar 

  25. Kao WY, Su CW, Chau GY, Lui WY, Wu CW, Wu JC. A comparison of prognosis between patients with hepatitis B and C virus-related hepatocellular carcinoma undergoing resection surgery. World J Surg. 2011;35(4):858–67.

    Article  PubMed  Google Scholar 

  26. Barazani Y, Hiatt JR, Tong MJ, Busuttil RW. Chronic viral hepatitis and hepatocellular carcinoma. World J Surg. 2007;31(6):1243–8.

    Article  PubMed  Google Scholar 

  27. Huo TI, Wu JC, Hsia CY, Chau GY, Lui WY, Huang YH, Lee PC, Chang FY, Lee SD. Hepatitis C virus infection is a risk factor for tumor recurrence after resection of small hepatocellular carcinomas. World J Surg. 2004;28(8):787–91.

    Article  PubMed  Google Scholar 

  28. McGivern DR, Lemon SM. Virus-specific mechanisms of carcinogenesis in hepatitis C virus associated liver cancer. Oncogene. 2011;30(17):1969–83.

    Article  PubMed  CAS  Google Scholar 

  29. 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 

  30. Cha CH, Ruo L, Fong Y, Jarnagin WR, Shia J, Blumgart LH, DeMatteo RP. Resection of hepatocellular carcinoma in patients otherwise eligible for transplantation. Ann Surg. 2003;238(3):315–21; discussion 321-3.

    PubMed  Google Scholar 

  31. Bozorgzadeh A, Orloff M, Abt P, Tsoulfas G, Younan D, Kashyap R, Jain A, Mantry P, Maliakkal B, Khorana A, Schwartz S. Survival outcomes in liver transplantation for hepatocellular carcinoma, comparing impact of hepatitis C versus other etiology of cirrhosis. Liver Transpl. 2007;13(6):807–13.

    Article  PubMed  Google Scholar 

  32. Shimoda M, Ghobrial RM, Carmody IC, Anselmo DM, Farmer DG, Yersiz H, Chen P, Dawson S, Durazo F, Han S, Goldstein LI, Saab S, Hiatt J, Busuttil RW. Predictors of survival after liver transplantation for hepatocellular carcinoma associated with hepatitis C. Liver Transpl. 2004;10(12):1478–86.

    Article  PubMed  Google Scholar 

  33. Moya A, Berenguer M, Aguilera V, Juan FS, Nicolas D, Pastor M, Lopez-Andujar R, Rayon M, Orbis F, Mora J, De Juan M, Carrasco D, Vila JJ, Prieto M, Berenguer J, Mir J. Hepatocellular carcinoma: can it be considered a controversial indication for liver transplantation in centers with high rates of hepatitis C? Liver Transpl. 2002;8(11):1020–7.

    Article  PubMed  Google Scholar 

  34. Tanimoto Y, Tashiro H, Aikata H, Amano H, Oshita A, Kobayashi T, Kuroda S, Tazawa H, Takahashi S, Itamoto T, Chayama K, Ohdan H. Impact of pegylated interferon therapy on outcomes of patients with hepatitis C virus-related hepatocellular carcinoma after curative hepatic resection. Ann Surg Oncol. 2012;19(2):418–25.

    Article  PubMed  Google Scholar 

  35. Shirabe K, Takeishi K, Taketomi A, Uchiyama H, Kayashima H, Maehara Y. Improvement of long-term outcomes in hepatitis C virus antibody-positive patients with hepatocellular carcinoma after hepatectomy in the modern era. World J Surg. 2011;35(5):1072–84.

    Article  PubMed  Google Scholar 

  36. Nathan H, Schulick RD, Choti MA, Pawlik TM. Predictors of survival after resection of early hepatocellular carcinoma. Ann Surg. 2009;249(5):799–805.

    Article  PubMed  Google Scholar 

  37. Scatton O, Zalinski S, Terris B, Lefevre JH, Casali A, Massault PP, Conti F, Calmus Y, Soubrane O. Hepatocellular carcinoma developed on compensated cirrhosis: resection as a selection tool for liver transplantation. Liver Transpl. 2008;14(6):779–88.

    Article  PubMed  Google Scholar 

  38. Katz SC, Shia J, Liau KH, Gonen M, Ruo L, Jarnagin WR, Fong Y, D’Angelica MI, Blumgart LH, Dematteo RP. Operative blood loss independently predicts recurrence and survival after resection of hepatocellular carcinoma. Ann Surg. 2009;249(4):617–23.

    Article  PubMed  Google Scholar 

  39. Hanazaki K, Kajikawa S, Shimozawa N, Mihara M, Shimada K, Hiraguri M, Koide N, Adachi W, Amano J. Survival and recurrence after hepatic resection of 386 consecutive patients with hepatocellular carcinoma. J Am Coll Surg. 2000;191(4):381–8.

    Article  PubMed  CAS  Google Scholar 

  40. Ishizuka M, Kubota K, Kita J, Shimoda M, Kato M, Sawada T. Duration of hepatic vascular inflow clamping and survival after liver resection for hepatocellular carcinoma. Br J Surg. 2011;98(9):1284–90.

    Article  PubMed  CAS  Google Scholar 

  41. Li H, Ge C, Zhao F, Yan M, Hu C, Jia D, Tian H, Zhu M, Chen T, Jiang G, Xie H, Cui Y, Gu J, Tu H, He X, Yao M, Liu Y, Li J. Hypoxia-inducible factor 1 alpha-activated angiopoietin-like protein 4 contributes to tumor metastasis via vascular cell adhesion molecule-1/integrin beta1 signaling in human hepatocellular carcinoma. Hepatology. 2011;54(3):910–9.

    Article  PubMed  CAS  Google Scholar 

  42. Xiaobin F, Shuguo Z, Jian Z, Yudong Q, Lijian L, Kuansheng M, Xiaowu L, Feng X, Dong Y, Shuguang W, Ping B, Jiahong D. Effect of the Pringle maneuver on tumor recurrence of hepatocellular carcinoma after curative resection (EPTRH): a randomized, prospective, controlled multicenter trial. BMC Cancer. 2012;12:340.

    Article  PubMed  Google Scholar 

  43. Liu L, Zhu XD, Wang WQ, Shen Y, Qin Y, Ren ZG, Sun HC, Tang ZY. Activation of beta-catenin by hypoxia in hepatocellular carcinoma contributes to enhanced metastatic potential and poor prognosis. Clin Cancer Res. 2010;16(10):2740–50.

    Article  PubMed  CAS  Google Scholar 

  44. Parfitt JR, Marotta P, Alghamdi M, Wall W, Khakhar A, Suskin NG, Quan D, McAllister V, Ghent C, Levstik M, McLean C, Chakrabarti S, Garcia B, Driman DK. Recurrent hepatocellular carcinoma after transplantation: use of a pathological score on explanted livers to predict recurrence. Liver Transpl. 2007;13(4):543–51.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Digestive Surgery, Hôpital Saint Antoine, 184, rue du faubourg Saint Antoine, 75012, Paris, France

    Mircea Chirica MD, Hadrien Tranchart MD, Viriane Tan MD, Matthieu Faron MD & François Paye MD, PhD

  2. University Pierre et Marie Curie, UPMC Paris VI, Paris, France

    Pierre Balladur MD, PhD & François Paye MD, PhD

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  1. Mircea Chirica MD
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Correspondence to François Paye MD, PhD.

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Chirica, M., Tranchart, H., Tan, V. et al. Infection with Hepatitis C Virus is an Adverse Prognostic Factor after Liver Resection for Early-stage Hepatocellular Carcinoma. Ann Surg Oncol 20, 2405–2412 (2013). https://doi.org/10.1245/s10434-012-2861-x

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  • DOI: https://doi.org/10.1245/s10434-012-2861-x

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