迟发移植物失功是肝移植的重要问题，其发病机制依然未知。杀伤免疫球蛋白样受体(KIRs) 能够调节NK细胞的细胞毒活性，而HLA-C是其主要的抑制性配体。根据其对HIR特异性，HLA-C等位基因分为两组，成为HLA-C1和HLA-C2。而HLA-C2对于NK细胞的活性有更强的抑制作用。我们研究了HLA-C基因型的对于大型肝移植队列患者的重要的临床意义，并发现至少1个HLA-C2等位基因的存在与较少的慢性排斥反应和移植物纤维化的组织学证据相关，10年的移植物丢失率下降16.2% (p = 0.003) (危害比: 2.7, 95% CI 1.4-5.3)且10年患者生存率升高13.6%(p = 0.01) (危害比: 1.9, 95% CI 1.1-3.3)。相比于HLA-C1纯合型的移植物，接受HLA-C2纯合型的移植物的患者10年移植物丢失率惊人地降低了26.5%(p < 0.001) (危害比: 7.2, 95% CI 2.2-23.0)。因此供者HLA-C基因型是肝移植后临床效果的主要决定因素，并提示了NK细胞在慢性排斥和移植物纤维化中的重要性。HLA-C和KIR相互作用的调节为提高移植物和患者的长期存活率提供了一种全新的途径。

Late allograft dysfunction is a significant problem following liver transplantation and its pathogenesis is uncertain. HLA-C is the major inhibitory ligand for killer immunoglobulin-like receptors (KIRs) that regulate the cytotoxic activity of natural killer (NK) cells. HLA-C alleles can be allocated into two groups, termed HLA-C1 and HLA-C2, based on their KIR specificity. HLA-C2 interactions are more inhibiting to NK cell activation. We studied the clinical importance of HLA-C genotype in a large liver transplant cohort and found that possession of at least one HLA-C2 allele by the donor allograft was associated with less histological evidence of chronic rejection and graft cirrhosis, a 16.2% reduction in graft loss (p = 0.003) (hazard ratio: 2.7, 95% CI 1.4-5.3) and a 13.6% improvement in patient survival (p = 0.01) (hazard ratio: 1.9, 95% CI 1.1-3.3) at 10 years. Transplantation of an HLA-C2 homozygous allograft led to a particularly striking 26.5% reduction in graft loss (p < 0.001) (hazard ratio: 7.2, 95% CI 2.2-23.0) at 10 years when compared to HLA-C1 homozygous allografts. Donor HLA-C genotype is therefore a major determinant of clinical outcome after liver transplantation and reveals the importance of NK cells in chronic rejection and graft cirrhosis. Modulation of HLA-C and KIR interactions represents an important novel approach to promote long-term graft and patient survival.