Advertisement

Indian Journal of Gastroenterology

, Volume 36, Issue 2, pp 117–125 | Cite as

Hepatocellular carcinoma biology predicts survival outcome after liver transplantation in the USA

  • Mohamed Abd El-Fattah
Original Article

Abstract

Purpose

The aim of this study is to evaluate the clinicopathologic prognostic factors of cancer-specific survival (CSS) in hepatocellular carcinoma (HCC) patients who underwent liver transplantation (LT) stratified by tumor size.

Methods

From the Surveillance, Epidemiology, and End Results (SEER) 18 registries (2004–2012), we retrieved data of 570 patients who underwent LT for a solitary primary HCC lesion ≤5 cm. A two multivariable Cox models were constructed to identify prognostic factors of CSS in a two different tumor sizes (2 cm cutoff).

Results

Out of 570 HCC patients (median age 57 years), 16% had microvascular invasion (MVI) and 12% had a poorly differentiated tumor. Male sex (odds ratio [OR] 2.6), tumor size >2 cm (OR 1.78), elevated AFP (OR 2.31), and poor tumor differentiation (OR 2.59) are significant predictors of MVI. With a median follow up of 41.5 months (range 1–107 months), the 5-year CSS rate was 90% in the absence of MVI compared to 75% in the presence of MVI (p<0.001). Multivariate models revealed that age ≥60 years (hazard ratio [HR] 2.08), MVI (HR 2.26), and poor tumor differentiation (HR 2.42), were significant risk factors of a dismal CSS with HCC size >2 cm, but not with HCC ≤2 cm.

Conclusions

Primary HCC tumor size ≤2 cm had an excellent prognosis after LT and was not affect by the presence of MVI or poor tumor differentiation.

Keywords

HCC Hepatocellular carcinoma Liver transplantation Microvascular invasion Prognosis 

Notes

Compliance with ethical standards

Funding

This study was not funded.

Conflict of interest

MA El-F declares that he has no conflict of interest.

Human informed consent

There were no human consents, as this study was a retrospective database report.

References

  1. 1.
    Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.CrossRefPubMedGoogle Scholar
  2. 2.
    El-Serag HB, Kanwal F. Epidemiology of hepatocellular carcinoma in the United States: where are we? Where do we go? Hepatology. 2014;60:1767–75.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Bruix J, Llovet JM. Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology. 2002;35:519–24.CrossRefPubMedGoogle Scholar
  4. 4.
    Doyle MB, Vachharajani N, Maynard E, et al. Liver transplantation for hepatocellular carcinoma: long-term results suggest excellent outcomes. J Am Coll Surg. 2012;215:19–28. discussion 28-30CrossRefPubMedGoogle Scholar
  5. 5.
    Tamura S, Kato T, Berho M, et al. Impact of histological grade of hepatocellular carcinoma on the outcome of liver transplantation. Arch Surg. 2001;136:25–30. discussion 31CrossRefPubMedGoogle Scholar
  6. 6.
    Iwatsuki S, Gordon RD, Shaw BW Jr, Starzl TE. Role of liver transplantation in cancer therapy. Ann Surg. 1985;202:401–7.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Cillo U, Vitale A, Bassanello M, et al. Liver transplantation for the treatment of moderately or well-differentiated hepatocellular carcinoma. Ann Surg. 2004;239:150–9.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Hwang S, Lee YJ, Kim KH, et al. The impact of tumor size on long-term survival outcomes after resection of solitary hepatocellular carcinoma: single-institution experience with 2558 patients. J Gastrointest Surg. 2015;19:1281–90.CrossRefPubMedGoogle Scholar
  10. 10.
    Oishi K, Itamoto T, Amano H, et al. Clinicopathologic features of poorly differentiated hepatocellular carcinoma. J Surg Oncol. 2007;95:311–6.CrossRefPubMedGoogle Scholar
  11. 11.
    Roayaie S, Blume IN, Thung SN, et al. A system of classifying microvascular invasion to predict outcome after resection in patients with hepatocellular carcinoma. Gastroenterology. 2009;137:850–5.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Han K, Tzimas GN, Barkun JS, et al. Preoperative alpha-fetoprotein slope is predictive of hepatocellular carcinoma recurrence after livertransplantation. Can J Gastroenterol. 2007;21:39–45.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Yao FY, Saab S, Bass NM, et al. Prediction of survival after liver retransplantation for late graft failure based on preoperative prognosticscores. Hepatology. 2004;39:230–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Jonas S, Bechstein WO, Steinmüller T, et al. Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis. Hepatology. 2001;33:1080–6.CrossRefPubMedGoogle Scholar
  15. 15.
    Shindoh J, Andreou A, Aloia TA, et al. Microvascular invasion does not predict long-term survival in hepatocellular carcinoma up to 2 cm: reappraisal of the staging system for solitary tumors. Ann Surg Oncol. 2013;20:1223–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Roayaie S, Obeidat K, Sposito C, et al. Resection of hepatocellular cancer ≤2 cm: results from two Western centers. Hepatology. 2013;57:1426–35.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Yamashita Y, Tsuijita E, Takeishi K, et al. Predictors for microinvasion of small hepatocellular carcinoma ≤2 cm. Ann Surg Oncol. 2012;19:2027–34.CrossRefPubMedGoogle Scholar
  18. 18.
    Fritz A, Percy C, Jack A, et al. International classification of diseases for oncology (ed 3). Geneva: Switzerland, World Health Organization; 2000.Google Scholar
  19. 19.
    El-Fattah MA, Aboelmagd M, Elhamouly M. Prognostic factors of hepatocellular carcinoma survival after radiofrequency ablation: a US population-based study. United European Gastroenterol J. 2016; doi: 10.1177/2050640616659024.PubMedPubMedCentralGoogle Scholar
  20. 20.
    El-Serag HB, Davila JA. Is fibrolamellar carcinoma different from hepatocellular carcinoma? A US population-based study. Hepatology. 2004;39:798–803.CrossRefPubMedGoogle Scholar
  21. 21.
    Shimada S, Kamiyama T, Yokoo H, et al. Clinicopathological characteristics and prognostic factors in young patients after hepatectomy for hepatocellular carcinoma. World J Surg Oncol. 2013;11:52.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Chen CH, Chang TT, Cheng KS, et al. Do young hepatocellular carcinoma patients have worse prognosis? The paradox of age as a prognostic factor in the survival of hepatocellular carcinoma patients. Liver Int. 2006;26:766–73.CrossRefPubMedGoogle Scholar
  23. 23.
    Niederle IM, Wörns MA, Koch S, et al. Clinicopathologic features and prognosis of young patients with hepatocellular carcinoma in a large German cohort. J Clin Gastroenterol. 2012;46:775–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Kim JH, Choi MS, Lee H, et al. Clinical features and prognosis of hepatocellular carcinoma in young patients from a hepatitis B-endemicarea. J Gastroenterol Hepatol. 2006;21:588–94.CrossRefPubMedGoogle Scholar
  25. 25.
    Yamazaki Y, Kakizaki S, Sohara N, et al. Hepatocellular carcinoma in young adults: the clinical characteristics, prognosis, and findings of a patient survival analysis. Dig Dis Sci. 2007;52:1103–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Mazzaferro V, Llovet JM, Miceli R, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10:35–43.CrossRefPubMedGoogle Scholar
  27. 27.
    Hyeon J, Ahn S, Lee JJ, Song DH, Park CK. Prognostic significance of BCL9 expression in hepatocellular carcinoma. Korean J Pathol. 2013;47:130–6.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Shah SA, Tan JC, McGilvray ID, et al. Does microvascular invasion affect outcomes after liver transplantation for HCC? A histopathological analysis of 155 consecutive explants. J Gastrointest Surg. 2007;11:464–71.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Fan L, Mac MT, Frishberg DP, et al. Interobserver and intraobserver variability in evaluating vascular invasion in hepatocellular carcinoma. J Gastroenterol Hepatol. 2010;25:1556–61.CrossRefPubMedGoogle Scholar
  30. 30.
    Mazzaferro V, Bhoori S, Sposito C, et al. Milan criteria in liver transplantation for hepatocellular carcinoma: an evidence-based analysis of 15 years of experience. Liver Transpl. 2011;17:S44–57.CrossRefPubMedGoogle Scholar
  31. 31.
    Sumie S, Kuromatsu R, Okuda K, et al. Microvascular invasion in patients with hepatocellular carcinoma and its predictable clinicopathological factors. Ann Surg Oncol. 2008;15:1375–82.CrossRefPubMedGoogle Scholar
  32. 32.
    Sala M, Fuster J, Llovet JM, et al. High pathological risk of recurrence after surgical resection for hepatocellular carcinoma: an indication for salvage liver transplantation. Liver Transpl. 2004;10:1294–300.CrossRefPubMedGoogle Scholar
  33. 33.
    Tangkijvanich P, Mahachai V, Suwangool P, Poovorawan Y. Gender difference in clinicopathologic features and survival of patients with hepatocellular carcinoma. World J Gastroenterol. 2004;10:1547–50.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Esnaola NF, Lauwers GY, Mirza NQ, et al. Predictors of microvascular invasion in patients with hepatocellular carcinoma who are candidates for orthotopic liver transplantation. J Gastrointest Surg. 2002;6:224–32. discussion 232CrossRefPubMedGoogle Scholar
  35. 35.
    McHugh PP, Gilbert J, Vera S, Koch A, Ranjan D, Gedaly R. Alpha-fetoprotein and tumour size are associated with microvascular invasion in explanted livers of patients undergoing transplantation with hepatocellular carcinoma. HPB (Oxford). 2010;12:56–61.CrossRefGoogle Scholar
  36. 36.
    Shirabe K, Itoh S, Yoshizumi T, et al. The predictors of microvascular invasion in candidates for liver transplantation with hepatocellular carcinoma—with special reference to the serum levels of des-gamma-carboxy prothrombin. J Surg Oncol. 2007;95:235–40.CrossRefPubMedGoogle Scholar
  37. 37.
    Kornberg A, Freesmeyer M, Bärthel E, et al. 18F-FDG-uptake of hepatocellular carcinoma on PET predicts microvascular tumor invasion in liver transplant patients. Am J Transplant. 2009;9:592–600.CrossRefPubMedGoogle Scholar
  38. 38.
    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.CrossRefPubMedGoogle Scholar
  39. 39.
    Hameed B, Mehta N, Sapisochin G, Roberts JP, Yao FY. Alpha-fetoprotein level >1000 ng/mL as an exclusion criterion for liver transplantation in patients with hepatocellular carcinoma meeting the Milan criteria. Liver Transpl. 2014;20:945–51.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Shetty K, Timmins K, Brensinger C, et al. Liver transplantation for hepatocellular carcinoma validation of present selection criteria in predicting outcome. Liver Transpl. 2004;10:911–8.CrossRefPubMedGoogle Scholar
  41. 41.
    Huang ZY, Liang BY, Xiong M, et al. Severity of cirrhosis should determine the operative modality for patients with early hepatocellular carcinoma and compensated liver function. Surgery. 2016;159:621–31.CrossRefPubMedGoogle Scholar
  42. 42.
    Esnaola NF, Mirza N, Lauwers GY, et al. Comparison of clinicopathologic characteristics and outcomes after resection in patients with hepatocellular carcinoma treated in the United States, France, and Japan. Ann Surg. 2003;238:711–9.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Zheng SS, Xu X, Wu J, et al. Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation. 2008;85:1726–32.CrossRefPubMedGoogle Scholar
  44. 44.
    Jun L, Zhenlin Y, Renyan G, et al. Independent factors and predictive score for extrahepatic metastasis of hepatocellular carcinoma following curative hepatectomy. Oncologist. 2012;17:963–9.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Lu Y, Zhu M, Li W, et al. Alpha fetoprotein plays a critical role in promoting metastasis of hepatocellular carcinoma cells. J Cell Mol Med. 2016;20:549–58.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Duvoux C, Roudot-Thoraval F, Decaens T, et al. Liver transplantation for hepatocellular carcinoma: a model including α-fetoprotein improves the performance of Milan criteria. Gastroenterology. 2012;143:986–94.CrossRefPubMedGoogle Scholar
  47. 47.
    Jin T, Peng H, Wu H. Clinical value of circulating liver cancer cells for the diagnosis of hepatocellular carcinoma: a meta-analysis. Biomed Rep. 2013;1:731–6.PubMedPubMedCentralGoogle Scholar

Copyright information

© Indian Society of Gastroenterology 2017

Authors and Affiliations

  1. 1.Department of Internal Medicine, Faculty of MedicineSuez Canal UniversityIsmailiaEgypt

Personalised recommendations