Expression of SREBF2 and HMGCR discriminates the viability of steatotic grafts for human liver transplantation
Baulies, Anna (Hospital Clínic i Provincial de Barcelona)
Torres, Sandra (Hospital Clínic i Provincial de Barcelona)
Fucho, Raquel (Hospital Clínic i Provincial de Barcelona)
Núñez Pereira, Susana (Hospital Clínic i Provincial de Barcelona)
Torres, Ferran (Universitat Autònoma de Barcelona. Departament de Pediatria, Obstetrícia i Ginecologia i de Medicina Preventiva i Salut Pública)
Ferrer-Fàbrega, Joana (Hospital Clínic i Provincial de Barcelona)
Díaz, Alba (Hospital Clínic i Provincial de Barcelona)
Rico, Naira (Hospital Clínic i Provincial de Barcelona)
García-Valdecasas, Juan Carlos (Hospital Clínic i Provincial de Barcelona)
Fuster, Josep (Hospital Clínic i Provincial de Barcelona)
Adàlia, Ramon (Hospital Clínic i Provincial de Barcelona)
Paredes, David (Hospital Clínic i Provincial de Barcelona)
Rimola, Antoni (Hospital Clínic i Provincial de Barcelona)
Fernández-Checa, José C. (Hospital Clínic i Provincial de Barcelona)
García-Ruiz, Carmen (Hospital Clínic i Provincial de Barcelona)

Data:	2025
Resum:	Hepatic steatosis presents a rising challenge in liver transplantation (LT), yet the precise underlying players remain incompletely understood. As steatosis reflects the accumulation of several types of lipids, including cholesterol, which has emerged as a key player in metabolic-dysfunction associated fatty liver disease, we aimed to characterize the content of lipids and the expression of cholesterol metabolic genes in liver biopsies before (pre-LT) and after LT (post-LT), with the ultimate goal of identifying factors that may impact graft loss and the overall outcomes of LT. Lipid content and cholesterol-related genes in pre- and post-LT graft biopsies, clinical outcome, and survival within the first year after LT were analyzed in 174 patients. Unlike free fatty acids (FFA) and triglycerides, total and free cholesterol (FC) levels are maintained in pre- and post-LT samples. Increased FC and FFA levels in pre-LT samples were associated with early allograft dysfunction (EAD). The increase in the expression of cholesterol regulatory genes SREBF2 and HMGCR in pre-LT samples was identified as a potential risk factor of death after LT, particularly with SREBF2, whose expression is associated with EAD and graft loss (GL). Collectively, these data link the expression of genes involved in the synthesis of cholesterol to LT-related mortality. These findings may translate to an increased application of marginal steatotic grafts in LT, thereby promoting a safe outcome.
Ajuts:	Agencia Estatal de Investigación PID2022-140169OB-C22 Generalitat de Catalunya 2021/SGR-00491 European Commission 101095679
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Liver transplantation ; Cholesterol ; Lipid profile ; Steatotic grafts ; Graft loss
Publicat a:	Journal of Lipid Research, Vol. 66, Num. 10 (October 2025) , art. 100901, ISSN 1539-7262

DOI: 10.1016/j.jlr.2025.100901
PMID: 40967384

15 p, 5.9 MB

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