NON-INVASIVE METHODS FOR ASSESSING HEPATIC GRAFT STEATOSIS IN A DECEASED DONOR WHO IS DECLARED BRAIN-DEAD
Abstract
The increase in the number of patients requiring liver transplantation raises the question of expanding and clarifying the criteria of hepatic grafts suitability for transplantation, and also shows the need to develop new, fast and noninvasive methods for assessing the functional state of the liver at the stage of donor examination and treatment. Hepatic grafts with severe steatosis, previously considered unsuitable for transplantation due to the higher risk of primary graft failure, are now referred to as potential for transplantation. There are several ways to diagnose and determine the stage of steatosis, but, unfortunately, today none of them can give an accurate and rapid assessment of its grade in a hepatic graft. Currently, the "gold standard" for determining liver steatosis is a biopsy with subsequent examination of samples by a pathomorphologist. There are also prognostic models, non-invasive tests and instrumental methods, the effectiveness of which has been proven - these are ultrasound elastography, contrast computed tomography and contrast computed tomography with liver density measurement. The decision on the suitability of a hepatic graft for transplantation depends on many factors, both on the part of the donor and on the part of the recipient, and it would be correct to assume that these data should be taken into account in aggregate. The review covers all the approaches currently used to quantify and qualitatively assess steatosis in liver transplants from a brain-dead donor.
References
Aehling NF, Seehofer D, Berg T. [Liver transplantation – current trends].Dtsch Med Wochenschr. 2020;145(16):1124-1131. https://doi.org/10.1055/a-0982-0737. (German).
Cesaretti M, Addeo P, Schiavo L, Anty R, Iannelli A. Assessment of Liver Graft Steatosis: Where Do We Stand? Liver Transpl. 2019;25(3):500-509. https://doi.org/10.1002/lt.25379.
Gill MG, Majumdar A. Metabolic associated fatty liver disease: Addressing a new era in liver transplantation. World J Hepatol. 2020;12(12):1168-1181. https://doi.org/10.4254/wjh.v12.i12.1168.
Chen XB, Xu MQ. Primary graft dysfunction after liver transplantation. Hepatobiliary Pancreat Dis Int. 2014;13(2):125-37. https://doi.org/10.1016/s1499-3872(14)60023-0.
Zhou J, Chen J, Wei Q, Saeb-Parsy K, Xu X. The Role of Ischemia/Reperfusion Injury in Early Hepatic Allograft Dysfunction. Liver Transpl. 2020;26(8):1034-1048. https://doi.org/10.1002/lt.25779.
Todo S, Demetris AJ, Makowka L, Teperman L, Podesta L, Shaver T, Tzakis A, Starzl TE. Primary nonfunction of hepatic allografts with preexisting fatty infiltration. Transplantation. 1989;47(5):903-5. https://doi.org/10.1097/00007890-198905000-00034.
D’Alessandro AM, Kalayoglu M, Sollinger HW, Hoffmann RM, Reed A, Knechtle SJ, Pirsch JD, Hafez GR, Lorentzen D, Belzer FO. The predictive value of donor liver biopsies for the development of primary nonfunction after orthotopic liver transplantation. Transplantation. 1991;51(1):157-63. https://doi.org/10.1097/00007890-199101000-00024.
Ploeg RJ, D’Alessandro AM, Knechtle SJ, Stegall MD, Pirsch JD, Hoffmann RM, Sasaki T, Sollinger HW, Belzer FO, Kalayoglu M. Risk factors for primary dysfunction after liver transplantation – a multivariate analysis. Transplantation. 1993;55(4):807-13. https://doi.org/10.1097/00007890-199304000-00024.
Carr RM, Oranu A, Khungar V. Nonalcoholic Fatty Liver Disease: Pathophysiology and Management. Gastroenterol Clin North Am. 2016;45(4):639-652. https://doi.org/10.1016/j.gtc.2016.07.003.
Sanyal AJ, Brunt EM, Kleiner DE, Kowdley KV, Chalasani N, Lavine JE, Ratziu V, McCullough A. Endpoints and clinical trial design for nonalcoholic steatohepatitis. Hepatology. 2011;54(1):344-53. https://doi.org/10.1002/hep.24376.
Eslam M, Sanyal AJ, George J; International Consensus Panel. MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology. 2020;158(7):1999-2014. https://doi.org/10.1053/j.gastro.2019.11.312.
Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Romero-Gomez M, Zelber-Sagi S, Wai-Sun Wong V, Dufour JF, Schattenberg JM, Kawaguchi T, Arrese M, Valenti L, Shiha G, Tiribelli C, Yki-Järvinen H, Fan JG, Grønbæk H, Yilmaz Y, Cortez-Pinto H, Oliveira CP, Bedossa P, Adams LA, Zheng MH, Fouad Y, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol. 2020;73(1):202-209. https://doi.org/10.1016/j.jhep.2020.03.039.
Adam R, Karam V, Cailliez V, O Grady JG, Mirza D, Cherqui D, Klempnauer J, Salizzoni M, Pratschke J, Jamieson N, Hidalgo E, Paul A, Andujar RL, Lerut J, Fisher L, Boudjema K, Fondevila C, Soubrane O, Bachellier P, Pinna AD, Berlakovich G, Bennet W, Pinzani M, Schemmer P, Zieniewicz K, Romero CJ, De Simone P, et al. 2018 Annual Report of the European Liver Transplant Registry (ELTR) – 50-year evolution of liver transplantation. Transpl Int. 2018;31(12):1293-1317. https://doi.org/10.1111/tri.13358.
Rehm J, Taylor B, Mohapatra S, Irving H, Baliunas D, Patra J, Roerecke M. Alcohol as a risk factor for liver cirrhosis: a systematic review and meta-analysis. Drug Alcohol Rev. 2010;29(4):437-45. https://doi.org/10.1111/j.1465-3362.2009.00153.x.
Gill MG, Majumdar A. Metabolic associated fatty liver disease: Addressing a new era in liver transplantation. World J Hepatol. 2020;12(12):1168-1181. https://doi.org/10.4254/wjh.v12.i12.1168.
Jou J, Choi SS, Diehl AM. Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin Liver Dis. 2008;28(4):370-9. https://doi.org/10.1055/s-0028-1091981.
Podymova SD. Jevoljucija predstavlenij o nealkogolnoj zhirovoj bolezni pecheni. Jeksperimentalnaja i klinicheskaja gastrojenterologija [Experimental & clinical gastroenterology]. 2009;4:4-12. (Russian).
Osna NA, Donohue TM Jr, Kharbanda KK. Alcoholic Liver Disease: Pathogenesis and Current Management. Alcohol Res. 2017;38(2):147-161.
Seitz HK, Bataller R, Cortez-Pinto H, Gao B, Gual A, Lackner C, Mathurin P, Mueller S, Szabo G, Tsukamoto H. Alcoholic liver disease. Nat Rev Dis Primers. 2018;4(1):16. https://doi.org/10.1038/s41572-018-0014-7.
Zhong Z, Connor H, Mason RP, Qu W, Stachlewitz RF, Gao W, Lemasters JJ, Thurman RG. Destruction of Kupffer cells increases survival and reduces graft injury after transplantation of fatty livers from ethanol-treated rats. Liver Transpl Surg. 1996;2(5):383-7. https://doi.org/10.1002/lt.500020509.
Álvarez-Mercado AI, Gulfo J, Romero Gómez M, JiménezCastro MB, Gracia-Sancho J, Peralta C. Use of Steatotic Grafts in Liver Transplantation: Current Status. Liver Transpl. 2019;25(5):771-786. https://doi.org/10.1002/lt.25430.
Ijaz S, Yang W, Winslet MC, Seifalian AM. Impairment of hepatic microcirculation in fatty liver. Microcirculation. 2003;10(6):447-56. https://doi.org/10.1038/sj.mn.7800206.
Fernández L, Carrasco-Chaumel E, Serafín A, Xaus C, Grande L, Rimola A, Roselló-Catafau J, Peralta C. Is ischemic preconditioning a useful strategy in steatotic liver transplantation? Am J Transplant. 2004;4(6):888-99. https://doi.org/10.1111/j.1600-6143.2004.00447.x.
Castera L, Friedrich-Rust M, Loomba R. Noninvasive Assessment of Liver Disease in Patients with Nonalcoholic Fatty Liver Disease. Gastroenterology. 2019;156(5):1264-1281. https://doi.org/10.1053/j.gastro.2018.12.036.
Rosenberger LH, Gillen JR, Hranjec T, Stokes JB, Brayman KL, Kumer SC, Schmitt TM, Sawyer RG. Donor risk index predicts graft failure reliably but not post-transplant infections. Surg Infect. 2014;15(2):94-8. https://doi.org/10.1089/sur.2013.035.
Spitzer AL, Lao OB, Dick AA, Bakthavatsalam R, Halldorson JB, Yeh MM, Upton MP, Reyes JD, Perkins JD. The biopsied donor liver: incorporating macrosteatosis into high-risk donor assessment. Liver Transpl. 2010;16(7):874-84. https://doi.org/10.1002/lt.22085.
Dutkowski P, Schlegel A, Slankamenac K, Oberkofler CE, Adam R, Burroughs AK, Schadde E, Müllhaupt B, Clavien PA. The use of fatty liver grafts in modern allocation systems: risk assessment by the balance of risk (BAR) score. Ann Surg. 2012;256(5):861-8. https://doi.org/10.1097/SLA.0b013e318272dea2.
Briceño J, Cruz-Ramírez M, Prieto M, Navasa M, Ortiz de Urbina J, Orti R, Gómez-Bravo MÁ, Otero A, Varo E, Tomé S, Clemente G, Bañares R, Bárcena R, CuervasMons V, Solórzano G, Vinaixa C, Rubín A, Colmenero J, Valdivieso A, Ciria R, Hervás-Martínez C, de la Mata M. Use of artificial intelligence as an innovative donor-recipient matching model for liver transplantation: results from a multicenter Spanish study. J Hepatol. 2014;61(5):1020-8. https://doi.org/10.1016/j.jhep.2014.05.039.
Poynard T, Ratziu V, Naveau S, Thabut D, Charlotte F, Messous D, Capron D, Abella A, Massard J, Ngo Y, Munteanu M, Mercadier A, Manns M, Albrecht J. The diagnostic value of biomarkers (SteatoTest) for the prediction of liver steatosis. Comp Hepatol. 2005;4:10. https://doi.org/10.1186/1476-5926-4-10.
Poynard T, Peta V, Munteanu M, Charlotte F, Ngo Y, Ngo A, Perazzo H, Deckmyn O, Pais R, Mathurin P, Myers R, Loomba R, Ratziu V. The diagnostic performance of a simplified blood test (SteatoTest-2) for the prediction of liver steatosis. Eur J Gastroenterol Hepatol. 2019;31(3):393-402. https://doi.org/10.1097/MEG.0000000000001304.
Calori G, Lattuada G, Ragogna F, Garancini MP, Crosignani P, Villa M, Bosi E, Ruotolo G, Piemonti L, Perseghin G. Fatty liver index and mortality: the Cremona study in the 15th year of follow-up. Hepatology. 2011;54(1):145-52. https://doi.org/10.1002/hep.24356.
de Lédinghen V, Vergniol J, Capdepont M, Chermak F, Hiriart JB, Cassinotto C, Merrouche W, Foucher J, Brigitte le B. Controlled attenuation parameter (CAP) for the diagnosis of steatosis: a prospective study of 5323 examinations. J Hepatol. 2014;60(5):1026-31. https://doi.org/10.1016/j.jhep.2013.12.018.
Cuthbertson DJ, Weickert MO, Lythgoe D, Sprung VS, Dobson R, Shoajee-Moradie F, Umpleby M, Pfeiffer AF, Thomas EL, Bell JD, Jones H, Kemp GJ. External validation of the fatty liver index and lipid accumulation product indices, using 1H-magnetic resonance spectroscopy, to identify hepatic steatosis in healthy controls and obese, insulin-resistant individuals. Eur J Endocrinol. 2014;171(5):561-9. https://doi.org/10.1530/EJE-14-0112.
Castera L, Vilgrain V, Angulo P. Noninvasive evaluation of NAFLD. Nat Rev Gastroenterol Hepatol. 2013;10(11):666-75. https://doi.org/10.1038/nrgastro.2013.175.
Fedchuk L, Nascimbeni F, Pais R, Charlotte F, Housset C, Ratziu V; LIDO Study Group. Performance and limitations of steatosis biomarkers in patients with nonalcoholic fatty liver disease. Aliment Pharmacol Ther. 2014;40(10):1209-22. https://doi.org/10.1111/apt.12963.
Hernaez R, Lazo M, Bonekamp S, Kamel I, Brancati FL, Guallar E, Clark JM. Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis. Hepatology. 2011;54(3):1082-1090. https://doi.org/10.1002/hep.24452.
Park SH, Kim PN, Kim KW, Lee SW, Yoon SE, Park SW, Ha HK, Lee MG, Hwang S, Lee SG, Yu ES, Cho EY. Macrovesicular hepatic steatosis in living liver donors: use of CT for quantitative and qualitative assessment. Radiology. 2006;239(1):105-12. https://doi.org/10.1148/radiol.2391050361.
Yoon JH, Lee JM, Suh KS, Lee KW, Yi NJ, Lee KB, Han JK, Choi BI. Combined Use of MR Fat Quantification and MR Elastography in Living Liver Donors: Can It Reduce the Need for Preoperative Liver Biopsy? Radiology. 2015;276(2):453-64. https://doi.org/10.1148/radiol.15140908.
Bril F, Ortiz-Lopez C, Lomonaco R, Orsak B, Freckleton M, Chintapalli K, Hardies J, Lai S, Solano F, Tio F, Cusi K. Clinical value of liver ultrasound for the diagnosis of nonalcoholic fatty liver disease in overweight and obese patients. Liver Int. 2015;35(9):2139-46. https://doi.org/10.1111/liv.12840.
Rogier J, Roullet S, Cornélis F, Biais M, Quinart A, Revel P, Bioulac-Sage P, Le Bail B. Noninvasive assessment of macrovesicular liver steatosis in cadaveric donors based on computed tomography liver-to-spleen attenuation ratio. Liver Transpl. 2015;21(5):690-5. https://doi.org/10.1002/lt.24105.
McCormack L, Dutkowski P, El-Badry AM, Clavien PA. Liver transplantation using fatty livers: always feasible? J Hepatol. 2011;54(5):1055-62. https://doi.org/10.1016/j.jhep.2010.11.004.
Markin RS, Wisecarver JL, Radio SJ, Stratta RJ, Langnas AN, Hirst K, Shaw BW Jr. Frozen section evaluation of donor livers before transplantation. Transplantation. 1993;56(6):1403-9. https://doi.org/10.1097/00007890-199312000-00025.
Deroose JP, Kazemier G, Zondervan P, Ijzermans JN, Metselaar HJ, Alwayn IP. Hepatic steatosis is not always a contraindication for cadaveric liver transplantation. HPB (Oxford). 2011;13(6):417-25. https://doi.org/10.1111/j.1477-2574.2011.00310.x.
Gabrielli M, Moisan F, Vidal M, Duarte I, Jiménez M, Izquierdo G, Domínguez P, Méndez J, Soza A, Benitez C, Pérez R, Arrese M, Guerra J, Jarufe N, Martínez J. Steatotic livers. Can we use them in OLTX? Outcome data from a prospective baseline liver biopsy study. Ann Hepatol. 2012;11(6):891-8. https://doi.org/10.1016/S1665-2681(19)31415-2.
de Graaf EL, Kench J, Dilworth P, Shackel NA, Strasser SI, Joseph D, Pleass H, Crawford M, McCaughan GW, Verran DJ. Grade of deceased donor liver macrovesicular steatosis impacts graft and recipient outcomes more than the Donor Risk Index. J Gastroenterol Hepatol. 2012;27(3):540-6. https://doi.org/10.1111/j.1440-1746.2011.06844.x.
Shiff JuR, Sorrel MF, Mjeddrej US. Bolezni pecheni po Shiffu. Cirroz pecheni i ego oslozhnenija. Transplantacija pecheni. Moskva: GJEOTAR-Media; 2012. p. 42. (Russian).
Imber CJ, St Peter SD, Lopez I, Guiver L, Friend PJ. Current practice regarding the use of fatty livers: a trans-Atlantic survey. Liver Transpl. 2002;8(6):545-9. https://doi.org/10.1053/jlts.2002.31747.
Zamboni F, Franchello A, David E, Rocca G, Ricchiuti A, Lavezzo B, Rizzetto M, Salizzoni M. Effect of macrovescicular steatosis and other donor and recipient characteristics on the outcome of liver transplantation. Clin Transplant. 2001;15(1):53-7. https://doi.org/10.1034/j.1399-0012.2001.150109.x.
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