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Background: Donors with hyperbilirubinemia are often not utilized for liver transplantation (LT) due to concerns about potential liver dysfunction and graft survival. The potential to mitigate organ shortages using such donors remains unclear. Methods: This study analyzed adult deceased donor data from the United Network for Organ Sharing database (2002–2022). Hyperbilirubinemia was categorized as high total bilirubin (3.0–5.0 mg/dL) and very high bilirubin (≥5.0 mg/dL) in brain‐dead donors. We assessed the impact of donor hyperbilirubinemia on 3‐month and 3‐year graft survival, comparing these outcomes to donors after circulatory death (DCD). Results: Of 138 622 donors, 3452 (2.5%) had high bilirubin and 1999 (1.4%) had very high bilirubin levels. Utilization rates for normal, high, and very high bilirubin groups were 73.5%, 56.4%, and 29.2%, respectively. No significant differences were found in 3‐month and 3‐year graft survival between groups. Donors with high bilirubin had superior 3‐year graft survival compared to DCD (hazard ratio.83, p =.02). Factors associated with inferior short‐term graft survival included recipient medical condition in intensive care unit (ICU) and longer cold ischemic time; factors associated with inferior long‐term graft survival included older donor age, recipient medical condition in ICU, older recipient age, and longer cold ischemic time. Donors with ≥10% macrosteatosis in the very high bilirubin group were also associated with worse 3‐year graft survival (p =.04). Discussion: The study suggests that despite many grafts with hyperbilirubinemia being non‐utilized, acceptable post‐LT outcomes can be achieved using donors with hyperbilirubinemia. Careful selection may increase utilization and expand the donor pool without negatively affecting graft outcome. [ABSTRACT FROM AUTHOR]

Hepatic stellate cells (HSCs) store retinoids and triacylglycerols in cytoplasmic lipid droplets. Two prominent features of HSC activation in liver fibrosis are loss of lipid droplets along with increase of α-smooth muscle actin (α-SMA), but the link between these responses and HSC activation remains elusive. In non-adipose cells, adipose differentiation-related protein (ADRP) coats lipid droplets and regulates their formation and lipolysis; however its function in HSCs is unknown. Here, we observed, in human liver sections or primary HSC culture, ADRP localization to lipid droplets of HSCs, and reduced staining coincident with loss of lipid droplets in liver fibrosis and in culture-activated HSCs, consistent with HSC activation. In the LX-2 human immortalized HSCs, with scant lipid droplets and features of activated HSCs, we found that the upregulation of ADRP mRNA by palmitate is potentiated by retinol, accompanied by increased ADRP protein, generation of retinyl palmitate, and lipid droplet formation. ADRP induction also led to decreased expression of α-SMA mRNA and its protein, while ADRP knockdown with small interfering RNA (siRNA) normalized α-SMA expression. Furthermore, ADRP induction by retinol and palmitate resulted in decreased expression of collagen I and matrix metalloproteinase-2 mRNA, fibrogenic genes associated with activated HSCs, while increasing matrix metalloproteinase-1 mRNA; ADRP knockdown with siRNA reversed these changes. Tissue inhibitor of metalloproteinase-1 was not affected. Thus, ADRP upregulation mediated by retinol and palmitate promotes downregulation of HSC activation and is functionally linked to the expression of fibrogenic genes. J. Cell. Physiol. 223:648–657, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Singh et al papers. To view these articles, visit https://doi.org/10.1111/apt.15633 and https://doi.org/10.1111/apt.15666. [ABSTRACT FROM AUTHOR]