The quality and size of liver grafts are critical factors that influence living-donor liver transplantation (LDLT) function and safety. However, the biomarkers used for predicting graft quality are lacking. In this study, we sought to identify unique graft quality markers, aside from donor age, by using the livers of non-human primates. Hepatic gene microarray expression data from young and elderly cynomolgus macaques revealed a total of 271 genes with significantly increased expression in the elderly. These candidate genes were then narrowed down to six through bioinformatics analyses. The expression patterns of these candidate genes in human donor liver tissues were subsequently examined. Importantly, we found that grafts exhibiting up-regulated expression of these six candidate genes were associated with an increased incidence of liver graft failure. Multivariable analysis further revealed that up-regulated expression of LRRN2 (encoding leucine-rich repeat protein, neuronal 2) in donor liver tissue served as an independent risk factor for graft failure (odds ratio 4.50, confidence interval 2.08-9.72). Stratification based on graft expression of LRRN2 and donor age was also significantly associated with 6-month graft survival rates. Conclusion: Up-regulated LRRN2 expression of liver graft is significantly correlated with graft failure in LDLT. In addition, combination of graft LRRN2 expression and donor age may represent a promising marker for predicting LDLT graft quality.
© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.