Future economics of liver transplantation: A 20-year cost modeling forecast and the prospect of bioengineering autologous liver grafts

PLoS ONE

Volumn 10, Issue 7, 2015, Pages

  Habka, Dany ^a   Mann, David ^a   Landes, Ronald ^a   Soto Gutierrez, Alejandro ^a,b,c,d  

^a Health Systems Reform ^*  (United States)

^b UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

^d UNIVERSITY OF PITTSBURGH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; AUTOLOGOUS LIVER GRAFT; BIOENGINEERING; COMPARATIVE STUDY; CONTROLLED STUDY; COST MODELING FORECAST; ECONOMIC MODEL; FACTUAL DATABASE; FORECASTING; GENERAL EPIDEMIOLOGY MODEL; HEALTH CARE COST; HEALTH CARE POLICY; HEALTH DISPARITY; HEALTH ECONOMICS; HOSPITAL ADMISSION EPIDEMIOLOGY MODEL; HOSPITAL ADMISSION TREATMENT COST MODEL; HUMAN; LIVER GRAFT; LIVER TRANSPLANTATION; MAJOR CLINICAL STUDY; MODEL FOR END STAGE LIVER DISEASE SCORE; MORTALITY; NONBIOLOGICAL MODEL; PATIENT; PLURIPOTENT STEM CELL; POST TRANSPLANT RELATED COST; POST TRANSPLANTATION EPIDEMIOLOGY MODEL; POST TRANSPLANTATION TREATMENT COST MODEL; PRE TRANSPLANT RELATED COST; PRE TRANSPLANTATION EPIDEMIOLOGY MODEL; PRE TRANSPLANTATION TREATMENT COST MODEL; RESOURCE ALLOCATION; SENSITIVITY ANALYSIS; SURGICAL PATIENT; TRANSPLANT RELATED COST; UNCERTAINTY; WAIT LISTED PATIENT; AUTOTRANSPLANTATION; ECONOMICS; END STAGE LIVER DISEASE; MALE; PATHOLOGY; SEVERITY OF ILLNESS INDEX;

BIOENGINEERING; END STAGE LIVER DISEASE; HUMANS; LIVER TRANSPLANTATION; MALE; MODELS, ECONOMIC; SEVERITY OF ILLNESS INDEX; TRANSPLANTATION, AUTOLOGOUS; UNCERTAINTY;

EID: 84941365920     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0131764     Document Type: Article

References (57)

1. Hoyert DL, Xu J. Deaths: preliminary data for 2011. Natl Vital Stat Rep. 2012; 61(6):1-51. PMID: 24984457.
2. Alqahtani SA. Update in liver transplantation. Curr Opin Gastroenterol. 2012; 28(3):230-8. doi: 10. 1097/MOG.0b013e3283527f16 PMID: 22450898.
3. Jimenez-Romero C, Caso Maestro O, Cambra Molero F, Justo Alonso I, Alegre Torrado C, Manrique Municio A, et al. Using old liver grafts for liver transplantation: where are the limits? World J Gastroenterol. 2014; 20(31):10691-702. doi: 10.3748/wjg.v20.i31.10691 PMID: 25152573; PubMed Central PMCID: PMC4138450.
4. U.S. Department of Health & Human Services HRaSA. Organ Procurement and Transplantation Network (OPTN). Available: http://optn.transplant.hrsa.gov/.
5. Busuttil RW, Tanaka K. The utility of marginal donors in liver transplantation. Liver Transpl. 2003; 9 (7):651-63. doi: 10.1053/jlts.2003.50105 PMID: 12827549.
6. Zarrinpar A, Busuttil RW. Liver transplantation: past, present and future. Nat Rev Gastroenterol Hepatol. 2013; 10(7):434-40. doi: 10.1038/nrgastro.2013.88 PMID: 23752825.
7. Graham JA, Guarrera JV. "Resuscitation" of marginal liver allografts for transplantation with machine perfusion technology. J Hepatol. 2014; 61(2):418-31. doi: 10.1016/j.jhep.2014.04.019 PMID: 24768755.
8. Cooper DK, Hara H, Ezzelarab M, Bottino R, Trucco M, Phelps C, et al. The potential of geneticallyengineered pigs in providing an alternative source of organs and cells for transplantation. J Biomed Res. 2013; 27(4):249-53. doi: 10.7555/JBR.27.20130063 PMID: 23885264; PubMed Central PMCID: PMC3721033.
9. Soltys KA, Soto-Gutierrez A, Nagaya M, Baskin KM, Deutsch M, Ito R, et al. Barriers to the successful treatment of liver disease by hepatocyte transplantation. J Hepatol. 2010; 53(4):769-74. doi: 10.1016/j. jhep.2010.05.010 PMID: 20667616; PubMed Central PMCID: PMC2930077.
10. Ciria R, Davila D, Heaton N. Auxiliary liver transplantation in children. Curr Opin Organ Transplant. 2011; 16(5):489-93. doi: 10.1097/MOT.0b013e32834a94cf PMID: 21897245.
11. Converter of current to real US dollars (using GDP deflator) 2014 [cited 2014 6th November 2015]. Available: http://stats.areppim.com/calc/calc-usdlrxdeflator.php.
12. Yen EF, Hardinger K, Brennan DC, Woodward RS, Desai NM, Crippin JS, et al. Cost-effectiveness of extending Medicare coverage of immunosuppressive medications to the life of a kidney transplant. Am J Transplant. 2004; 4(10):1703-8. doi: 10.1111/j.1600-6143.2004.00565.x PMID: 15367228.
13. Torgerson D, Raftery J. Economics notes: measuring outcomes in economic evaluations. BMJ. 1999; 318(7195):1413. PMID: 10334758; PubMed Central PMCID: PMC1115785.
14. (SRTR) OPaTNOaSRoTR. OPTN/SRTR 2012 Annual Data Report. Rockville, MD: Department of Health and Human Services, Health Resources and Services Administration. 2014:1-185.
15. Wiesner R, Edwards E, Freeman R, Harper A, Kim R, Kamath P, et al. Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology. 2003; 124(1):91-6. doi: 10.1053/gast. 2003.50016 PMID: 12512033.
16. Showstack J, Katz PP, Lake JR, Brown RS Jr., Dudley RA, Belle S, et al. Resource utilization in liver transplantation: effects of patient characteristics and clinical practice. NIDDK Liver Transplantation Database Group. JAMA. 1999; 281(15):1381-6. PMID: 10217053.
17. Washburn WK, Pollock BH, Nichols L, Speeg KV, Halff G. Impact of recipient MELD score on resource utilization. Am J Transplant. 2006; 6(10):2449-54. doi: 10.1111/j.1600-6143.2006.01490.x PMID: 16889598.
18. Bentley TS, Hanson SG, Hauboldt RH. 2011 U.S. organ and tissue transplant cost estimates and disscussion. Milliman Research Report. 2011:2-16.
19. California Pacific Medical Center website 2014. Available: http://www.cpmc.org/advanced/liver/patients/topics/finance.html.
20. Longworth L, Young T, Buxton MJ, Ratcliffe J, Neuberger J, Burroughs A, et al. Midterm cost-effectiveness of the liver transplantation program of England and Wales for three disease groups. Liver Transpl. 2003; 9(12):1295-307. doi: 10.1016/j.lts.2003.09.012 PMID: 14625830.
21. Ammori JB, Pelletier SJ, Lynch R, Cohn J, Ads Y, Campbell DA, et al. Incremental costs of post-liver transplantation complications. J Am Coll Surg. 2008; 206(1):89-95. doi: 10.1016/j.jamcollsurg.2007. 06.292 PMID: 18155573.
22. Global Health Expenditure Database [Internet]. World Health Organization 2014. Available: http://apps. who.int/nha/database/Select/Indicators/en.
23. Axelrod DA, Dzebisashvili N, Lentine K, Segev DL, Dickson R, Tuttle-Newhall E, et al. Assessing variation in the costs of care among patients awaiting liver transplantation. Am J Transplant. 2014; 14(1):70-8 doi: 10.1111/ajt.12494 PMID: 24165015.
24. Baptista PM, Siddiqui MM, Lozier G, Rodriguez SR, Atala A, Soker S. The use of whole organ decellularization for the generation of a vascularized liver organoid. Hepatology. 2011; 53(2):604-17. doi: 10. 1002/hep.24067 PMID: 21274881.
25. Ott HC, Clippinger B, Conrad C, Schuetz C, Pomerantseva I, Ikonomou L, et al. Regeneration and orthotopic transplantation of a bioartificial lung. Nat Med. 2010; 16(8):927-33. doi: 10.1038/nm.2193 PMID: 20628374.
26. Ott HC, Matthiesen TS, Goh SK, Black LD, Kren SM, Netoff TI, et al. Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart. Nat Med. 2008; 14(2):213-21. doi: 10.1038/nm1684 PMID: 18193059.
27. Petersen TH, Calle EA, Zhao L, Lee EJ, Gui L, Raredon MB, et al. Tissue-engineered lungs for in vivo implantation. Science. 2010; 329(5991):538-41. doi: 10.1126/science.1189345 PMID: 20576850; PubMed Central PMCID: PMC3640463.
28. Song JJ, Guyette JP, Gilpin SE, Gonzalez G, Vacanti JP, Ott HC. Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat Med. 2013; 19(5):646-51. doi: 10.1038/nm. 3154 PMID: 23584091; PubMed Central PMCID: PMC3650107.
29. Uygun BE, Soto-Gutierrez A, Yagi H, Izamis ML, Guzzardi MA, Shulman C, et al. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med. 2010; 16(7):814-20. doi: 10.1038/nm.2170 PMID: 20543851; PubMed Central PMCID: PMC2930603.
30. Yagi H, Fukumitsu K, Fukuda K, Kitago M, Shinoda M, Obara H, et al. Human-scale whole-organ bioengineering for liver transplantation: a regenerative medicine approach. Cell Transplant. 2013; 22 (2):231-42. doi: 10.3727/096368912X654939 PMID: 22943797; PubMed Central PMCID: PMC3682787.
31. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007; 131(5):861-72. Epub 2007/11/24. doi: 10.1016/j.cell.2007.11.019 PMID: 18035408.
32. Sohlenius-Sternbeck AK. Determination of the hepatocellularity number for human, dog, rabbit, rat and mouse livers from protein concentration measurements. Toxicol In Vitro. 2006; 20(8):1582-6. doi: 10. 1016/j.tiv.2006.06.003 PMID: 16930941.
33. Si-Tayeb K, Lemaigre FP, Duncan SA. Organogenesis and development of the liver. Dev Cell. 2010; 18(2):175-89. doi: 10.1016/j.devcel.2010.01.011 PMID: 20159590.
34. Blouin A, Bolender RP, Weibel ER. Distribution of organelles and membranes between hepatocytes and nonhepatocytes in the rat liver parenchyma. A stereological study. J Cell Biol. 1977; 72(2):441-55. PMID: 833203; PubMed Central PMCID: PMC2110997.
35. Menzin J, White LA, Nichols C, Deniz B. The economic burden of advanced liver disease among patients with hepatitis C virus: a large state Medicaid perspective. BMC Health Serv Res. 2012; 12:459. doi: 10.1186/1472-6963-12-459 PMID: 23241078; PubMed Central PMCID: PMC3529684.
36. Inc. GS. Harvoni (Ledipasvir and Sofosbuvir) tablets for oral use: US prescribing information. European Medicines Agency. 2015.
37. Harvoni (ledipasvir/sofosbuvir) film-coated tablets: EU summary of product characteristics. 2014.
38. Pawlotsky J-M. Hepatitis C treatment: the data flood goes on-An update from the liver meeting 2014. Gastroenterology. 2015; 148(3):468-79. Epub 2015 Jan 7. doi: 10.1053/j.gastro.2015.01.002 PMID: 25576860
39. Hoofnagle JH, Sherker AH. Therapy for hepatitis C-the costs of success. N Engl J Med. 2014; 370 (16):1552-3. doi: 10.1056/NEJMe1401508 PMID: 24725236.
40. Denniston MM, Jiles RB, Drobeniuc J, Klevens RM, Ward JW, McQuillan GM, et al. Chronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010. Ann Intern Med. 2014; 160(5):293-300. doi: 10.7326/M13-1133 PMID: 24737271.
41. Wong RJ, Aguilar M, Cheung R, Perumpail RB, Harrison SA, Younossi ZM, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology. 2015; 148(3):547-55. doi: 10.1053/j.gastro.2014.11.039 PMID: 25461851.
42. Geissler EK, Hutchinson JA. Cell therapy as a strategy to minimize maintenance immunosuppression in solid organ transplant recipients. Curr Opin Organ Transplant. 2013; 18(4):408-15. doi: 10.1097/MOT.0b013e328363319d PMID: 23838645.
43. Buchanan P, Dzebisashvili N, Lentine KL, Axelrod DA, Schnitzler MA, Salvalaggio PR. Liver transplantation cost in the model for end-stage liver disease era: looking beyond the transplant admission. Liver Transpl. 2009; 15(10):1270-7. doi: 10.1002/lt.21802 PMID: 19790155.
44. Schnitzler MA, Whiting JF, Brennan DC, Lentine KL, Desai NM, Chapman W, et al. The life-years saved by a deceased organ donor. Am J Transplant. 2005; 5(9):2289-96. doi: 10.1111/j.1600-6143. 2005.01021.x PMID: 16095511.
45. Schnitzler MA, Woodward RS, Brennan DC, Whiting JF, Tesi RJ, Lowell JA. The economic impact of preservation time in cadaveric liver transplantation. Am J Transplant. 2001; 1(4):360-5. PMID: 12099381.
46. Salvalaggio PR, Dzebisashvili N, MacLeod KE, Lentine KL, Gheorghian A, Schnitzler MA, et al. The interaction among donor characteristics, severity of liver disease, and the cost of liver transplantation. Liver Transpl. 2011; 17(3):233-42. doi: 10.1002/lt.22230 PMID: 21384505.
47. Soto-Gutierrez A, Wertheim JA, Ott HC, Gilbert TW. Perspectives on whole-organ assembly: moving toward transplantation on demand. J Clin Invest. 2012; 122(11):3817-23. doi: 10.1172/JCI61974 PMID: 23114604; PubMed Central PMCID: PMC3484436.
48. Sullivan GJ, Hay DC, Park IH, Fletcher J, Hannoun Z, Payne CM, et al. Generation of functional human hepatic endoderm from human induced pluripotent stem cells. Hepatology. 2010; 51(1):329-35. doi: 10.1002/hep.23335 PMID: 19877180; PubMed Central PMCID: PMC2799548.
49. Si-Tayeb K, Noto FK, Nagaoka M, Li J, Battle MA, Duris C, et al. Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology. 2010; 51(1):297-305. doi: 10. 1002/hep.23354 PMID: 19998274; PubMed Central PMCID: PMC2946078.
50. Ulvestad M, Nordell P, Asplund A, Rehnstrom M, Jacobsson S, Holmgren G, et al. Drug metabolizing enzyme and transporter protein profiles of hepatocytes derived from human embryonic and induced pluripotent stem cells. Biochem Pharmacol. 2013; 86(5):691-702. doi: 10.1016/j.bcp.2013.06.029 PMID: 23856292.
51. Ma X, Duan Y, Tschudy-Seney B, Roll G, Behbahan IS, Ahuja TP, et al. Highly efficient differentiation of functional hepatocytes from human induced pluripotent stem cells. Stem Cells Transl Med. 2013; 2 (6):409-19. doi: 10.5966/sctm.2012-0160 PMID: 23681950; PubMed Central PMCID: PMC3673753.
52. The Human Genome Project Completion: Frequently Asked Questions: National Human Genome Research Institute; 2010 [cited 2010 01/07/2015]. Available: http://www.genome.gov/11006943.
53. Yarbrough C, Thomson A. International Human Genome Sequencing Consortium Announces "Working Draft" of Human Genome 2000. Available: http://www.nih.gov/news/pr/jun2000/nhgri-26.htm.
54. Hayden EC. Technology: The $1,000 genome. Nature. 2014; 507(7492):294-5. doi: 10.1038/507294a PMID: 24646979.
55. Bredenkamp N, Ulyanchenko S, O'Neill KE, Manley NR, Vaidya HJ, Blackburn CC. An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts. Nat Cell Biol. 2014; 16(9):902-8. doi: 10.1038/ncb3023 PMID: 25150981; PubMed Central PMCID: PMC4153409.
56. Nishikawa T, Bell A, Brooks JM, Setoyama K, Melis M, Han B, et al. Resetting the transcription factor network reverses terminal chronic hepatic failure. J Clin Invest. 2015; 125(4):1533-44. doi: 10.1172/JCI73137 PMID: 25774505.
57. Song K, Nam YJ, Luo X, Qi X, Tan W, Huang GN, et al. Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature. 2012; 485(7400):599-604. doi: 10.1038/nature11139 PMID: 22660318; PubMed Central PMCID: PMC3367390.