Prognosis of Liver Transplantation for Hepatocellular Carcinoma in Terms of Different Criteria: A Single Center Experience

Abstract

Objective

Patients undergoing liver transplantation for hepatocellular carcinoma (HCC) within the Milan criteria have an excellent outcome. We developed a program to analyze and prove that the Milan criteria can be expanded safely and effectively.

Methods

We retrospectively reviewed 117 HCC patients treated with liver transplantation between January 2013 and December 2017. Patients were grouped according to the Milan criteria, the University of California, San Francisco (UCSF) criteria, Up-to-seven criteria and Hangzhou criteria. Tumor-free and overall survival rates were investigated with a Kaplan-Meier analysis. Multivariable regression Cox models produced survival estimates for the patients that exceeded the Milan criteria.

Results

The 1-year, 3-year and 5-year overall survival rates of patients fulfilling the Milan criteria (n=44) were 100%, 87.5% and 78.9%, respectively. Compared with the Milan criteria, the UCSF criteria (n=50), Up-to-seven criteria (n=51) and Hangzhou criteria (n=86) provided an expansion of 13.6%, 15.9% and 95.9%, respectively. The 1-year, 3-year and 5-year overall survival rates of patients fulfilling UCSF criteria, Up-to-seven criteria and Hangzhou criteria were 96.0%, 84.9%, 76.9%; 96.1%, 85.2%, 77.6% and 97.7%, 83.9%, 66.7%, respectively (P>0.05). Multifactor Cox regression showed that tumor diameter and microvascular invasion were independent risk factors for survival in patients that exceeded the Milan criteria.

Conclusion

Compared with the Milan criteria, the Hangzhou criteria can safely expand the scope of liver transplantation for HCC to a certain extent. By contrast, the UCSF criteria and Up-to-seven criteria result in a limited number of patients which need further expansion. Tumor diameter and microvascular invasion were the independent risk factors for survival in patients that exceeded the Milan criteria.

Keywords

liver transplantation / hepatocellular carcinoma / survival / Milan criteria

References

[1] BrayF, FerlayJ, SoerjomataramI, et al.. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424

[2] WangFS, FanJG, ZhangZ, et al.. The global burden of liver disease: The major impact of China. Hepatology, 2014, 60(6): 2099-2108

[3] OfosuA, GurakarA. Current concepts in hepatocellular carcinoma and liver transplantation: a review and 2014 update. Euroasian J Hepatogastroenterol, 2015, 5(1): 19-25

[4] AravinthanAD, BruniSG, DoyleAC, et al.. Liver transplantation is a preferable alternative to palliative therapy for selected patients with advanced hepatocellular carcinoma. Ann Surg Oncol, 2017, 24(7): 1843-1851

[5] KaidoT. Selection criteria and current issues in liver transplantation for hepatocellular carcinoma. Liver Cancer, 2016, 5(2): 121-127

[6] PavelMC, FusterJ. Expansion of the hepatocellular carcinoma Milan criteria in liver transplantation: Future directions. World J Gastroenterol, 2018, 24(32): 3626-3636

[7] KaidoT. Selection criteria and current issues in liver transplantation for hepatocellular carcinoma. Liver Cancer, 2016, 5(2): 121-127

[8] MancusoA, PerriconeG. Hepatocellular carcinoma and liver transplantation: state of the art. J Clin Transl Hepatol, 2014, 2(3): 176-181

[9] MazzaferroV, RegaliaE, DociR, et al.. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med, 1996, 334(11): 693-699

[10] GunsarF. Liver transplantation for hepatocellular carcinoma beyond the Milan criteria. Exp Clin Transplant, 2017, 15(Suppl 2): 59-64

[11] FanJ, YangGS, FuZR, et al.. Liver transplantation outcomes in 1078 hepatocellular carcinoma patients: a muticenter experience in Shanghai, China. J Cancer Res Clin Oncol, 2009, 135(10): 1403-1412

[12] Cascales-CamposP, Martinez-InsfranLA, RamirezP, et al.. Liver Transplantation in Patients With Hepatocellular Carcinoma Outside the Milan Criteria After Downstaging: Is It Worth It?. Transplant Proc, 2018, 50(2): 591-594

[13] LingiahVA, NiaziM, OlivoR, et al.. Liver Transplantation Beyond Milan Criteria. J Clin Transl Hepatol, 2020, 8(1): 69-75

[14] CommanderSJ, ShawB, WashburnL, et al.. A long-term experience with expansion of Milan criteria for liver transplant recipients. Clin Transplant, 2018, 32(6): e13254

[15] YaoFY, FerrellL, BassNM, et al.. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology, 2001, 33(6): 1394-1403

[16] DuffyJP, VardanianA, BenjaminE, et al.. Liver transplantation criteria for hepatocellular carcinoma should be expanded: a 22-yearexperience with 467 patients at UCLA. Ann Surg, 2007, 246(3): 502-509

[17] MazzaferroV, LlovetJM, MiceliRMetroticket Investigator Study Group, et al.. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol, 2009, 10(1): 35-43

[18] ZhengSS, XuX, WuJ, et al.. Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation, 2008, 85(12): 1726-1732

[19] QuZ, LingQ, GwiasdaJ, et al.. Hangzhou criteria are more accurate than Milan criteria in predicting long-term survival after liver transplantation for HCC in Germany. Langenbecks Arch Surg, 2018, 403(5): 643-654

[20] LeiJY, WangWT, YanLN. Hangzhou criteria for liver transplantation in hepatocellular carcinoma: a single-center experience. Eur J Gastroenterol Hepatol, 2014, 26(2): 200-204

[21] GuerriniGP, PinelliD, Di BenedettoF, et al.. Predictive value of nodule size and differentiation in HCC recurrence after liver transplantation. Surg Oncol, 2016, 25(4): 419-428

[22] PolatKY, AcarS, GencdalG, et al.. Hepatocellular Carcinoma and Liver Transplantation: A Single-Center Experience. Transplant Proc, 2020, 52(1): 259-264

[23] SorianoA, VaronaA, GianchandaniR, et al.. Selection of patients with hepatocellular carcinoma for liver transplantation: past and future. World J Hepatol, 2016, 8(1): 58-68

[24] XuX, LuD, LingQ, et al.. Liver transplantation for hepatocellular carcinoma beyond the Milan criteria. Gut, 2016, 65(6): 1035-1041