Morphologic and immunophenotypic evaluation of liver allograft biopsies with contemporaneous serum DSA measurements

Background: Acute antibody mediated rejection is increasingly identified in liver allografts as a unique form of alloimmune injury associated with donor specific antibodies (DSA). This manifests pathologically as microvascular injury and C4d uptake. Despite the liver allograft's relative resistance to alloimmune injury, liver allografts are not impervious to cellular and antibody-mediated rejection. Methods: In this blinded control study, we evaluated CD163 immunohistochemistry and applied the Banff 2016 criteria for diagnosis of acute AMR on a group of indication allograft liver biopsies from DSA positive patients and compared them to indication biopsies from DSA negative controls. Results: Most DSA positive patients were females (75%, p =.027), and underwent transplantation for HCV infection. Significant histopathological predictors of serum DSA positivity were Banff H-score (p =.01), moderate to severe cholestasis (p =.03), and CD163 score > 2 (p =.029). Other morphologic features that showed a trend with DSA positivity include Banff portal C4d-score (p =.06), bile ductular reaction (p =.07), and central perivenulitis (p =.07). The odds of DSA sMFI ≥5000 was 12.5 times higher in those with a C4d score >1 than those with a C4d score ≤ 1 (p =.04). Incidence of definite for aAMR in the DSA positive cohort was 25% (n = 5), and 0% in the DSA negative cohort. A group of 5 DSA positive cases were not classifiable by the current scheme. Conclusion: Sinusoidal CD163, Banff H-score, and diffuse C4d are predictors of serum DSA, and facilitate recognition of histopathological features associated with serum DSA and tissue–antibody interaction.