Liver, Pancreas and Biliary Tract|Articles in Press

The prognostic relationship between donor age and infectious risk in liver transplant patients with nonalcoholic steatohepatitis: Analysis of UNOS database

Published:February 15, 2023DOI:


      Background & Aims

      We investigate the effects of advancing donor age on the prognostic outcomes of patients with NASH who undergo liver transplant (LT), with a specialized attention toward infectious outcomes post-LT.


      The UNOS-STAR registry was used to select 2005 to 2019 LT recipients with NASH, who were stratified by donor age into the following categories: recipients with younger donors (less than 50 years of age–reference), quinquagenarian donors, sexagenarian donors, septuagenarian donors, and octogenarian donors. Cox regression analyses were conducted for all-cause mortality, graft failure, infectious causes of death.


      From a total of 8888 recipients, the quinquagenarian, septuagenarian, and octogenarian donor cohorts showed greater risk of all-cause mortality (quinquagenarian: aHR 1.16 95%CI 1.03–1.30; septuagenarian: aHR 1.20 95%CI 1.00–1.44; octogenarian: aHR 2.01 95%CI 1.40–2.88). With advancing donor age, there was an increased risk of death from sepsis (quinquagenarian: aHR 1.71 95% CI 1.24–2.36; sexagenarian: aHR 1.73 95% CI 1.21–2.48; septuagenarian: aHR 1.76 95% CI 1.07–2.90; octogenarian: aHR 3.58 95% CI 1.42–9.06) and infectious causes (quinquagenarian: aHR 1.46 95% CI 1.12–1.90; sexagenarian: aHR 1.58 95% CI 1.18–2.11; septuagenarian: aHR 1.73 95% CI 1.15–2.61; octogenarian: aHR 3.70 95% CI 1.78–7.69).


      NASH patients who receive grafts from elderly donors exhibit higher risk of post-LT mortality, especially due to infection.


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        • Katsarou A.
        • Moustakas I.I.
        • Pyrina I.
        • Lembessis P.
        • Koutsilieris M.
        • Chatzigeorgiou A
        Metabolic inflammation as an instigator of fibrosis during non-alcoholic fatty liver disease.
        World J Gastroenterol. 2020; 26: 1993-2011
        • Heyens L.J.M.
        • Busschots D.
        • Koek G.H.
        • Robaeys G.
        • Francque S
        Liver fibrosis in non-alcoholic fatty liver disease: from liver biopsy to non-invasive biomarkers in diagnosis and treatment.
        Front Med. 2021; 8615978
        • Gressner A.M
        Hepatic fibrogenesis: the puzzle of interacting cells, fibrogenic cytokines, regulatory loops, and extracellular matrix molecules.
        Z Gastroenterol. 1992; 30 Suppl 1: 5-16
        • Schultz G.S.
        • Wysocki A
        Interactions between extracellular matrix and growth factors in wound healing.
        Wound Repair Regen. 2009; 17: 153-162
        • Sullivan W.J.
        • Mullen P.J.
        • Schmid E.W.
        • et al.
        Extracellular matrix remodeling regulates glucose metabolism through TXNIP destabilization.
        Cell. 2018; 175 (e21): 117-132
        • Selicean S.
        • Wang C.
        • Guixé-Muntet S.
        • Stefanescu H.
        • Kawada N.
        • Gracia-Sancho J
        Regression of portal hypertension: underlying mechanisms and therapeutic strategies.
        Hepatol Int. 2021; 15: 36-50
        • Zipprich A.
        • Garcia-Tsao G.
        • Rogowski S.
        • Fleig W.E.
        • Seufferlein T.
        • Dollinger M.M
        Prognostic indicators of survival in patients with compensated and decompensated cirrhosis.
        Liver Int. 2012; 32: 1407-1414
        • Potosek J.
        • Curry M.
        • Buss M.
        • Chittenden E
        Integration of palliative care in end-stage liver disease and liver transplantation.
        J Palliat Med. 2014; 17: 1271-1277
        • O'Grady J
        Timing and benefit of liver transplantation in acute liver failure.
        J Hepatol. 2014; 60: 663-670
        • Nagai S.
        • Collins K.
        • Chau L.C.
        • et al.
        Increased risk of death in first year after liver transplantation among patients with nonalcoholic steatohepatitis vs liver disease of other etiologies.
        Clin Gastroenterol Hepatol. 2019; 17 (e5): 2759-2768
        • VanWagner L.B.
        • Lapin B.
        • Skaro A.I.
        • Lloyd-Jones D.M.
        • Rinella M.E
        Impact of renal impairment on cardiovascular disease mortality after liver transplantation for nonalcoholic steatohepatitis cirrhosis.
        Liver Int. 2015; 35: 2575-2583
        • Castelló B.
        • Aguilera V.
        • Blázquez M.T.
        • et al.
        Post-transplantation outcome in non-alcoholic steatohepatitis cirrhosis: comparison with alcoholic cirrhosis.
        Ann Hepatol. 2019; 18: 855-861
        • Kubota T.
        • Hata K.
        • Sozu T.
        • et al.
        Impact of donor age on recipient survival in adult-to-adult living-donor liver transplantation.
        Ann Surg. 2018; 267: 1126-1133
      1. Cuervas-Mons V., de la Rosa G., Pardo F., San Juan F., Valdivieso A., en representación del Registro Español de Trasplante Hepático. [Activity and results of liver transplantation in Spain during 1984-2012. Analysis of the Spanish Liver Transplant Registry]. Med Clin . 2015;144(8):337–47.

        • Anderson C.D.
        • Vachharajani N.
        • Doyle M.
        • et al.
        Advanced donor age alone does not affect patient or graft survival after liver transplantation.
        J Am Coll Surg. 2008; 207: 847-852
        • Machicao V.I.
        • Bonatti H.
        • Krishna M.
        • et al.
        Donor age affects fibrosis progression and graft survival after liver transplantation for hepatitis C.
        Transplantation. 2004; 77: 84-92
        • Wali M.
        • Harrison R.F.
        • Gow P.J.
        • Mutimer D
        Advancing donor liver age and rapid fibrosis progression following transplantation for hepatitis C.
        Gut. 2002; 51: 248-252
        • Zhou J.
        • Huang Z.
        • Chen Z.
        • Xu F.
        • Tong R.
        • Zheng S
        Impact of donor age on liver transplant outcomes in patients with hepatocellular carcinoma: analysis of the SRTR database.
        BMC Gastroenterol. 2021; 21: 195
        • Doycheva I.
        • Issa D.
        • Watt K.D.
        • Lopez R.
        • Rifai G.
        • Alkhouri N
        Nonalcoholic steatohepatitis is the most rapidly increasing indication for liver transplantation in young adults in the United States.
        J Clin Gastroenterol. 2018; 52: 339-346
        • Stahl E.C.
        • Haschak M.J.
        • Popovic B.
        • Brown B.N
        Macrophages in the aging liver and age-related liver disease.
        Front Immunol. 2018; 9: 2795
        • Fine J.P.
        • Gray R.J
        A proportional hazards model for the subdistribution of a competing risk.
        J Am Stat Assoc. 1999; 94: 496-509
      2. Pantanowitz A., Marwala T. Evaluating the Impact of Missing Data Imputation through the use of the Random Forest Algorithm. arXiv [statME]. Published online December 12, 2008.

        • Gayowski T.
        • Marino I.R.
        • Singh N.
        • et al.
        Orthotopic liver transplantation in high-risk patients.
        Transplantation. 1998; 65: 499-504
        • Wong R.J.
        • Singal A.K
        Trends in liver disease etiology among adults awaiting liver transplantation in the United States, 2014-2019.
        JAMA Netw Open. 2020; 3e1920294
        • Hunt N.J.
        • Kang S.W.S.
        • Lockwood G.P.
        • Le Couteur D.G.
        • Cogger V.C
        Hallmarks of aging in the liver.
        Comput Struct Biotechnol J. 2019; 17: 1151-1161
        • Videla L.A.
        • Tapia G.
        • Fernández V
        Influence of aging on Kupffer cell respiratory activity in relation to particle phagocytosis and oxidative stress parameters in mouse liver.
        Redox Rep. 2001; 6: 155-159
        • Kosugi I.
        • Muro H.
        • Shirasawa H.
        • Ito I
        Endocytosis of soluble IgG immune complex and its transport to lysosomes in hepatic sinusoidal endothelial cells.
        J Hepatol. 1992; 16: 106-114
        • Bilzer M.
        • Roggel F.
        • Gerbes A.L
        Role of Kupffer cells in host defense and liver disease.
        Liver Int. 2006; 26: 1175-1186
        • Maeso-Díaz R.
        • Ortega-Ribera M.
        • Fernández-Iglesias A.
        • et al.
        Effects of aging on liver microcirculatory function and sinusoidal phenotype.
        Aging Cell. 2018; 17: e12829
        • Terrault N.A.
        • Roland M.E.
        • Schiano T.
        • et al.
        Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection.
        Liver Transpl. 2012; 18: 716-726
        • Adam R.
        • Karam V.
        • Delvart V.
        • et al.
        Improved survival in liver transplant recipients receiving prolonged-release tacrolimus in the European Liver Transplant Registry.
        Am J Transplant. 2015; 15: 1267-1282
        • Hibi T.
        • Tanabe M.
        • Hoshino K.
        • et al.
        Cyclosporine A-based immunotherapy in adult living donor liver transplantation: accurate and improved therapeutic drug monitoring by 4-hr intravenous infusion.
        Transplantation. 2011; 92: 100-105
        • Levy G.
        • Grazi G.L.
        • Sanjuan F.
        • et al.
        12-month follow-up analysis of a multicenter, randomized, prospective trial in de novo liver transplant recipients (LIS2T) comparing cyclosporine microemulsion (C2 monitoring) and tacrolimus.
        Liver Transpl. 2006; 12: 1464-1472
        • Vandenbroucke J.P
        Prospective or retrospective: what's in a name?.
        BMJ. 1991; 302: 249-250
        • Gil E.
        • Kim J.M.
        • Jeon K.
        • et al.
        Recipient age and mortality after liver transplantation: a population-based cohort study.
        Transplantation. 2018; 102: 2025-2032