C4d immunopositivity is uncommon in ABO-compatible liver allografts, but correlates partially with lymphocytotoxic antibody status

Aims: To determine whether C4d immunopositivity helps recognition of humoral rejection in dysfunctional liver allografts. Methods and results: C4d immunopositivity was retrospectively evaluated in liver allografts. There were three staining patterns: portal venular plexus, sinusoidal and hepatocellular. The latter was related to ischaemic necrosis and not scored as positive. C4d immunopositivity was not encountered in 10 preperfusion or 15 consecutive early protocol biopsies. However, three of 12 early protocol biopsy specimens from crossmatch-positive patients were C4d+, two showing repeated positivity on at least one further biopsy specimen, while others remained negative. C4d was also positive in 2/16 early moderate acute cellular rejections, 3/14 cases of centrilobular necroinflammation, 3/11 biliary obstructions, 3/13 chronic rejections and 1/10 primary non-functional allografts. Conclusions: C4d immunopositivity is uncommon in liver allografts. There is a weak positive correlation with a positive lymphocytotoxic crossmatch and some patterns of allograft dysfunction. The morphological associations resemble those reported in lymphocytotoxic crossmatch-positive patients, plus occasional sinusoidal and hepatocellular injury. Although the practical utility of C4d immunohistochemistry seems limited, it may identify a small subgroup of individuals in whom chronic humoral microvascular injury contributes to allograft dysfunction.