Diagnostic performance of EUS-FNA for pancreatic lesions at tertiary centers in Iran without rapid on-site evaluation

Complement component 4 degradation product (C4d) staining is a routine ancillary tool in diagnosing antibody-mediated rejection (AMR) in renal and cardiac allografts, but its role in liver transplantation (LT) remains controversial, especially given the infrequency of AMR. This study aimed to assess the positivity and pattern of C4d staining in ABO-compatible (ABO-C) LT allografts with varying degrees of rejection.

In this retrospective cross-sectional study, we analyzed patients who received ABO-C LT between 2019 and 2021. We assessed the presence of AMR by evaluating C4d staining intensity and diffuseness using immunohistochemistry (IHC) on formalin-fixed paraffin-embedded liver tissue, which interpreted according to BANFF criteria. Donor-specific antibodies (DSAs), clinical, histological, and outcome data were also collected.

A total of 90 ABO-C LT recipients were included, with C4d data available for 47 subjects. Of these, 12 (25.5%) were C4d-positive based on BANFF criteria. C4d positivity was not significantly associated with mortality (P = 0.244), rejection (P = 0.310), or liver enzyme levels (i.e., AST, ALT, ALK; P = 0.958, 0.958, and 1.000, respectively). Additionally, the survival distributions for C4d + and C4d- groups were not significantly different (χ² = 1.599, P = 0.206). Twelve subjects had concomitant DSA and C4d data, but all were C4d-negative, limiting our ability to assess the diagnostic value of the C4d+/DSA+ immunophenotype. DSAs did not show a significant relationship with mortality or rejection either.

The limited availability of paired C4d and DSAs data in this cohort precluded a meaningful evaluation of their combined role in diagnosing AMR in ABO-compatible liver transplantation. In the absence of cases with concurrent C4d and DSA positivity, our findings are inconclusive regarding their diagnostic utility. Larger, prospective studies with complete datasets are required to clarify the value of integrating C4d, DSA, and clinicopathological features in AMR diagnosis.