Abstract
Background
There are no conclusive cost-effectiveness studies measuring the efficacy of salvage LT after liver resection (LR) and radiofrequency ablation (RFA) in patients with early hepatocellular carcinoma (HCC) and compensated cirrhosis. The aim of the present study is to compare liver transplantation (LT) versus locoregional therapy plus salvage LT (to treat tumor recurrence) in patients with early HCC and compensated cirrhosis.
Methods
Reference case: 55-year old male with HCC within Milan criteria and Child-Pugh A cirrhosis. The analysis was performed in two geographical cost settings: USA and Italy. Survival benefit measured in quality-adjusted life years (QALYs), costs (C) in US$, incremental cost-effectiveness, willingness to pay, and net health benefit (NHB).
Results
In the base-case analysis, NHB of LT vs. LR and RFA was −1.7 and −1.3 years for single tumor ≤3 cm, −1.2 and −0.7 for single nodules measuring 3.1–5 cm and −0.7 and −0.7 for multi-nodular tumor ≤3 cm in Italy. In USA, NHB of LT versus LR and RFA were −1.2 and −0.8 years for single tumor ≤3 cm, −0.9 and −0.5 for single nodules measuring 3.1–5 cm, and −0.5 and −0.4 for multi-nodular tumor ≤ 3 cm. On the Monte Carlo simulation, only young patients with multi-nodular HCC and short waiting list time had a positive NHB. Salvage LT proved to be an ineffective cost strategy after RFA or LR.
Conclusion
In patients with HCC within Milan criteria and Child-Pugh A cirrhosis, LR and RFA were more cost-effective than LT. Salvage LT was not cost-effective.
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References
Mazzaferro V, Regalia E, Doci R et al (1996) Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334:693–699
Bruix J, Sherman M (2011) American Association for the Study of Liver D Management of hepatocellular carcinoma: an update. Hepatology 53:1020–1022
Forner A, Hessheimer AJ, Isabel Real M et al (2006) Treatment of hepatocellular carcinoma. Crit Rev Oncol Hematol 60:89–98
Nathan H, Bridges JF, Schulick RD et al (2011) Understanding surgical decision making in early hepatocellular carcinoma. J Clin Oncol 29:619–625
Adam R, Bhangui P, Vibert E et al (2012) Resection or transplantation for early hepatocellular carcinoma in a cirrhotic liver: does size define the best oncological strategy? Ann Surg 256:883–891
Bismuth H, Chiche L, Adam R et al (1993) Liver resection versus transplantation for hepatocellular carcinoma in cirrhotic patients. Ann Surg 218:145–151
Cherqui D, Laurent A, Mocellin N et al (2009) Liver resection for transplantable hepatocellular carcinoma: long-term survival and role of secondary liver transplantation. Ann Surg 250:738–746
Park YK, Kim BW, Wang HJ et al (2009) Hepatic resection for hepatocellular carcinoma meeting Milan criteria in Child-Turcotte-Pugh class a patients with cirrhosis. Transpl Proc 41:1691–1697
Cunningham SC, Tsai S, Marques HP et al (2009) Management of early hepatocellular carcinoma in patients with well-compensated cirrhosis. Ann Surg Oncol 16:1820–1831
Ni JY, Xu LF, Sun HL et al (2013) Percutaneous ablation therapy versus surgical resection in the treatment for early-stage hepatocellular carcinoma: a meta-analysis of 21,494 patients. J Cancer Res Clin Oncol 139:2021–2033
Cucchetti A, Piscaglia F, Cescon M et al (2013) Cost-effectiveness of hepatic resection versus percutaneous radiofrequency ablation for early hepatocellular carcinoma. J Hepatol 59:300–307
Lim KC, Wang VW, Siddiqui FJ, et al.(2014) Cost-effectiveness analysis of liver resection versus transplantation for early hepatocellular carcinoma within the Milan criteria. Hepatology. doi:10.1002/hep.27135
Stinnett AA (1998) Mullahy J Net health benefits: a new framework for the analysis of uncertainty in cost-effectiveness analysis. Med Decis Making 18:S68–S80
Grosse SD (2008) Assessing cost-effectiveness in healthcare: history of the $50,000 per QALY threshold. Expert Rev Pharmacoecon Outcomes Res 8:165–178
Lang K, Danchenko N, Gondek K et al (2009) The burden of illness associated with hepatocellular carcinoma in the United States. J Hepatol 50:89–99
Mazzaferro V, Llovet JM, Miceli R et al (2009) Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol 10:35–43
Onaca N, Davis GL, Goldstein RM et al (2007) Expanded criteria for liver transplantation in patients with hepatocellular carcinoma: a report from the International Registry of Hepatic Tumors in Liver Transplantation. Liver Transpl 13:391–399
Volk ML, Vijan S, Marrero JA (2008) A novel model measuring the harm of transplanting hepatocellular carcinoma exceeding Milan criteria American journal of transplantation. J Am Soc Transpl Am Soc Transpl Surg 8:839–846
Beck JR, Kassirer JP, Pauker SG (1982) A convenient approximation of life expectancy (the “DEALE”). I. Validation of the method. Am J Med 73:883–888
Salvalaggio PR, Dzebisashvili N, MacLeod KE et al (2011) The interaction among donor characteristics, severity of liver disease, and the cost of liver transplantation. Liver Transpl 17:233–242
Trotter JF, Mackenzie S, Wachs M et al (2003) Comprehensive cost comparison of adult-adult right hepatic lobe living-donor liver transplantation with cadaveric transplantation. Transplantation 75:473–476
Sagmeister M, Mullhaupt B, Kadry Z et al (2002) Cost-effectiveness of cadaveric and living-donor liver transplantation. Transplantation 73:616–622
Sagmeister M, Renner EL, Mullhaupt B et al (2002) Simulation of hepatitis C based on a mandatory reporting system. Eur J Gastroenterol Hepatol 14:25–34
Majno PE, Sarasin FP, Mentha G et al (2000) 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 31:899–906
Fuks D, Dokmak S, Paradis V et al (2012) Benefit of initial resection of hepatocellular carcinoma followed by transplantation in case of recurrence: an intention-to-treat analysis. Hepatology 55:132–140
N’Kontchou G, Aout M, Laurent A et al (2012) Survival after radiofrequency ablation and salvage transplantation in patients with hepatocellular carcinoma and Child-Pugh A cirrhosis. J Hepatol 56:160–166
Vitale A, Volk ML, Pastorelli D et al (2010) Use of sorafenib in patients with hepatocellular carcinoma before liver transplantation: a cost-benefit analysis while awaiting data on sorafenib safety. Hepatology 51:165–173
Erlinge D, Gotberg M, Lang I et al (2014) Rapid endovascular catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction. The CHILL-MI trial: a randomized controlled study of the use of central venous catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction. J Am Coll Cardiol 63:1857–1865
Fenwick E, O’Brien BJ, Briggs A (2004) Cost-effectiveness acceptability curves–facts, fallacies and frequently asked questions. Health Econ 13:405–415
Siegel JE, Weinstein MC, Russell LB et al (1996) Recommendations for reporting cost-effectiveness analyses. Panel on Cost-Effectiveness in Health and Medicine. JAMA 276:1339–1341
Cucchetti A, Piscaglia F, Cescon M et al (2013) Systematic review of surgical resection vs radiofrequency ablation for hepatocellular carcinoma. World J Gastroenterol 19:4106–4118
Nathan H, Segev DL, Mayo SC et al (2012) National trends in surgical procedures for hepatocellular carcinoma: 1998-2008. Cancer 118:1838–1844
Washburn K, Edwards E, Harper A et al (2010) Hepatocellular carcinoma patients are advantaged in the current liver transplant allocation system. Am J Transpl 10:1643–1648
Landman MP, Feurer ID, Pinson CW et al (2011) Which is more cost-effective under the MELD system: primary liver transplantation, or salvage transplantation after hepatic resection or after loco-regional therapy for hepatocellular carcinoma within Milan criteria? HPB 13:783–791
Zimmerman MA, Ghobrial RM, Tong MJ et al (2008) Recurrence of hepatocellular carcinoma following liver transplantation: a review of preoperative and postoperative prognostic indicators Archives of surgery 143:182–188 discussion 188
Cha CH, Ruo L, Fong Y et al (2003) Resection of hepatocellular carcinoma in patients otherwise eligible for transplantation. Ann Surg 238:315–321 discussion 321-313
Xu XS, Liu C, Qu K et al (2014) Liver transplantation versus liver resection for hepatocellular carcinoma: a meta-analysis. Hepatobiliary Pancreat Dis Int 13:234–241
Izumi R, Shimizu K, Ii T et al (1994) Prognostic factors of hepatocellular carcinoma in patients undergoing hepatic resection. Gastroenterology 106:720–727
Cucchetti A, Vitale A, Del Gaudio M et al (2010) Harm and benefits of primary liver resection and salvage transplantation for hepatocellular carcinoma. Am J Transpl 10:619–627
Buscarini L, Buscarini E, Di Stasi M et al (2001) Percutaneous radiofrequency ablation of small hepatocellular carcinoma: long-term results. Eur Radiol 11:914–921
Lencioni R, Cioni D, Crocetti L et al (2005) Early-stage hepatocellular carcinoma in patients with cirrhosis: long-term results of percutaneous image-guided radiofrequency ablation. Radiology 234:961–967
Chou CT, Chou JM, Chang TA et al (2013) Differentiation between dysplastic nodule and early-stage hepatocellular carcinoma: the utility of conventional MR imaging. World J Gastroenterol 19:7433–7439
Poon RT, Fan ST, Lo CM et al (2002) 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 235:373–382
Chan AC, Chan SC, Chok KS et al (2013) Treatment strategy for recurrent hepatocellular carcinoma: salvage transplantation, repeated resection, or radiofrequency ablation? Liver transpl 19:411–419
Polesel J, Zucchetto A, Montella M et al (2009) The impact of obesity and diabetes mellitus on the risk of hepatocellular carcinoma. Ann Oncol 20:353–357
Naugler WE, Sonnenberg A (2010) Sonnenberg a survival and cost-effectiveness analysis of competing strategies in the management of small hepatocellular carcinoma. Liver Transpl 16:1186–1194
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Authors Gaya Spolverato and Alessandro Vitale contributed equally to this work.
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Spolverato, G., Vitale, A., Ejaz, A. et al. The Relative Net Health Benefit of Liver Resection, Ablation, and Transplantation for Early Hepatocellular Carcinoma. World J Surg 39, 1474–1484 (2015). https://doi.org/10.1007/s00268-015-2987-7
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DOI: https://doi.org/10.1007/s00268-015-2987-7