Skip to main content

Benefit of Treating Hepatocellular Carcinoma Recurrence after Liver Transplantation and Analysis of Prognostic Factors for Survival in a Large Euro-American Series

Annals of Surgical Oncology volume 22, pages 2286–2294 (2015)Cite this article

Abstract

Purpose

To identify prognostic factors after hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT).

Methods

We retrospectively reviewed the combined experience at Toronto General Hospital and Hospital Vall d’Hebron managing HCC recurrence after LT (n = 121) between 2000 and 2012. We analyzed prognostic factors by uni- and multi-variate analysis. Median follow-up from LT was 29.5 (range 2–129.4) months. Median follow-up from HCC recurrence was 12.2 (range 0.1–112.5) months.

Results

At recurrence, 31.4 % were treated with curative-intent treatments (surgery or ablation), 42.1 % received palliative treatment, and 26.4 % received best supportive care. The 1-, 3-, and 5-year survivals, respectively, after HCC recurrence were 75, 60, and 31 %, vs. 60, 19, and 12 %, vs. 52, 4, and 5 % (p < 0.001). By multivariate analysis, not being amenable to a curative-intent treatment [hazard ratio (HR) 4.7, 95 % confidence interval (CI) 2.7–8.3, p < 0.001], α-fetoprotein of ≥100 ng/mL at the time of HCC recurrence (HR 2.1, 95 % CI 1.3–2.3, p = 0.002) and early recurrence (<12 months) after LT (HR 1.6, 95 % CI 1.1–2.5, p = 0.03) were found to be poor prognosis factors. A prognostic score was devised on the basis of these three independent variables. Patients were divided into three groups, as follows: good prognosis, 0 points (n = 22); moderate prognosis, 1 or 2 points (n = 84); and poor prognosis, 3 points (n = 15). The 1-, 3-, and 5-year actuarial survival for each group was 91, 50, and 50 %, vs. 52, 7, and 2 %, vs. 13, 0, and 0 %, respectively (p < 0.001).

Conclusions

Patients with HCC recurrence after transplant amenable to curative-intent treatments can experience significant long-term survival (~50 % at 5 years), so aggressive management should be offered. Poor prognosis factors after recurrence are not being amenable to a curative-intent treatment, α-fetoprotein of ≥100 ng/mL, and early (<1 year) recurrence after LT.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

References

  1. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012;31:1245–55.

    Google Scholar 

  2. Yao FY. Liver transplantation for hepatocellular carcinoma: beyond the Milan criteria. Am J Transplant. 2008;8:1982–9.

    PubMed  Article  Google Scholar 

  3. Mazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiavo M, Mariani L, Camerini T, et al; Metroticket Investigator Study Group. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10:35–43.

    PubMed  Article  Google Scholar 

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

    PubMed  Article  Google Scholar 

  5. DuBay D, Sandroussi C, Sandhu L, Cleary S, Guba M, Cattral MS, McGilvray I, et al. Liver transplantation for advanced hepatocellular carcinoma using poor tumor differentiation on biopsy as an exclusion criterion. Ann Surg. 2011;253:166–72.

    PubMed  Article  Google Scholar 

  6. Jonas S, Bechstein WO, Steinmüller T, Herrmann M, Radke C, Berg T, Settmacher U, et al. Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis. Hepatology. 2001;33:1080–6.

    PubMed  Article  Google Scholar 

  7. Rodríguez-Perálvarez M, Luong TV, Andreana L, Meyer T, Dhillon AP, Burroughs AK. A systematic review of microvascular invasion in hepatocellular carcinoma: diagnostic and prognostic variability. Ann Surg Oncol. 2013;20:325–39.

    PubMed  Article  Google Scholar 

  8. Cillo U, Vitale A, Grigoletto F, Gringeri E, D’Amico F, Valmasoni M, Brolese A, et al. Intention-to-treat analysis of liver transplantation in selected, aggressively treated HCC patients exceeding the Milan criteria. Am J Transpl. 2007;7:972–81.

    PubMed  Article  Google Scholar 

  9. Toso C, Cader S, Mentha-Dugerdil A, Meeberg G, Majno P, Morard I, Giostra E, et al. Factors predicting survival after post-transplant hepatocellular carcinoma recurrence. J Hepatobiliary Pancreat Sci. 2013;20:342–7.

    PubMed  Google Scholar 

  10. Welker MW, Bechstein WO, Zeuzem S, Trojan J. Recurrent hepatocellular carcinoma after liver transplantation—an emerging clinical challenge. Transpl Int. 2013;26:109–18.

    PubMed  Article  Google Scholar 

  11. DuBay DA, Sandroussi C, Kachura JR, Ho CS, Beecroft JR, Vollmer CM, Ghanekar A, et al. Radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation. HPB (Oxford). 2011;13:24–32.

    PubMed Central  PubMed  Article  Google Scholar 

  12. Wo JY, Dawson LA, Zhu AX, Hong TS. An emerging role for radiation therapy in the treatment of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Surg Oncol Clin N Am. 2014;23:353–68.

    PubMed  Article  Google Scholar 

  13. Sapisochin G, Castells L, Dopazo C, Bilbao I, Minguez B, Lázaro JL, Allende H, et al. Single HCC in cirrhotic patients: liver resection or liver transplantation? Long-term outcome according to an intention-to-treat basis. Ann Surg Oncol. 2013;20:1194–202.

    PubMed  Article  Google Scholar 

  14. Valdivieso A, Bustamante J, Gastaca M, Uriarte JG, Ventoso A, Ruiz P, Fernandez JR, et al. Management of hepatocellular carcinoma recurrence after liver transplantation. Transpl Proc. 2010;42:660–2.

    PubMed  Article  Google Scholar 

  15. Pfiffer TE, Seehofer D, Nicolaou A, Neuhaus R, Riess H, Trappe RU. Recurrent hepatocellular carcinoma in liver transplant recipients: parameters affecting time to recurrence, treatment options and survival in the sorafenib era. Tumori. 2011;97:436–41.

    PubMed  Google Scholar 

  16. Taketomi A, Toshima T, Kitagawa D, Motomura T, Takeishi K, Mano Y, Kayashima H, et al. Predictors of extrahepatic recurrence after curative hepatectomy for hepatocellular carcinoma. Ann Surg Oncol. 2010;17:2740–6.

    PubMed  Google Scholar 

  17. Toso C, Mentha G, Majno P. Integrating sorafenib into an algorithm for the management of post-transplant hepatocellular carcinoma recurrence. J Hepatol. 2013;59:3–5.

    CAS  PubMed  Article  Google Scholar 

  18. Kornberg A, Küpper B, Tannapfel A, Katenkamp K, Thrum K, Habrecht O, Willberg J. Long-term survival after recurrent hepatocellular carcinoma in liver transplant patients: clinical patterns and outcome variables. Eur J Surg Oncol. 2010;36:275–80.

    PubMed  Article  Google Scholar 

  19. Roayaie S, Schwartz JD, Sung MW, Emre SH, Miller CM, Gondolesi GE, Krieger NR, et al. Recurrence of hepatocellular carcinoma after liver transplant: patterns and prognosis. Liver Transpl. 2004;10:534–44.

    Article  Google Scholar 

  20. Hameed B, Mehta N, Sapisochin G, Roberts JP, Yao FY. Alpha-fetoprotein >1000 ng/mL as an exclusion criterion for liver transplantation in patients with hepatocellular carcinoma meeting Milan criteria. Liver Transpl. 2014.

  21. Duvoux C, Roudot-Thoraval F, Decaens T, Pessione F, Badran H, Piardi T, Francoz C, et al; Liver Transplantation French Study Group. Liver transplantation for hepatocellular carcinoma: a model including α-fetoprotein improves the performance of Milan criteria. Gastroenterology. 2012;143:986–94.

    Article  Google Scholar 

  22. Shah SA, Cleary SP, Wei AC, Yang I, Taylor BR, Hemming AW, Langer B, et al. Recurrence after liver resection for hepatocellular carcinoma: risk factors, treatment, and outcomes. Surgery. 2007;141:330–9.

    PubMed  Article  Google Scholar 

Download references

Conflict of interest

The authors declare no conflict of interest.

Author information

Affiliations

  1. Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada

    G. Sapisochin MD, PhD, N. Goldaracena MD, J. M. Laurence MD, PhD, D. Davidson BSc, D. R. Grant MD, A. Ghanekar MD, PhD, I. D. McGilvray MD, PhD, M. S. Cattral MD, M. Selzner MD & P. D. Greig MD

  2. Department of HPB Surgery and Transplantation, Hospital Universitario Vall d’Hebron, Universidad Autónoma de Barcelona, Barcelona, Spain

    G. Sapisochin MD, PhD, S. Astete MD, L. Castells MD, PhD, I. Bilbao MD, PhD, C. Dopazo MD, PhD, J. L. Lázaro MD, M. Caralt MD, PhD & R. Charco MD, PhD

  3. Department of Transplantation, Skane University Hospital, Malmö, Sweden

    E. Rafael MD, PhD

  4. University of Sydney, Sydney, Australia

    C. Sandroussi MD

  5. Department of Medicine, Toronto General Hospital and University of Toronto, Toronto, Canada

    L Lilly MD

Authors
  1. G. Sapisochin MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. Goldaracena MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Astete MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. M. Laurence MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. Davidson BSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E. Rafael MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L. Castells MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C. Sandroussi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. I. Bilbao MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. C. Dopazo MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. D. R. Grant MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. J. L. Lázaro MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. M. Caralt MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. A. Ghanekar MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. I. D. McGilvray MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. L Lilly MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. M. S. Cattral MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. M. Selzner MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. R. Charco MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. P. D. Greig MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. Sapisochin MD, PhD.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sapisochin, G., Goldaracena, N., Astete, S. et al. Benefit of Treating Hepatocellular Carcinoma Recurrence after Liver Transplantation and Analysis of Prognostic Factors for Survival in a Large Euro-American Series. Ann Surg Oncol 22, 2286–2294 (2015). https://doi.org/10.1245/s10434-014-4273-6

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-014-4273-6

Keywords

  • Liver Transplantation
  • Sorafenib
  • Palliative Treatment
  • Early Recurrence
  • Prognostic Score