COVID-19-Related Cholangiopathy: Histological Findings

Abstract

Cholangiopathy has been described in survivors of severe COVID-19, presenting significant clinical parallels to the pre-pandemic condition of secondary sclerosing cholangitis in critically ill patients (SSC-CIP). We aimed to examine the liver histopathology of individuals with persistent cholestasis after severe COVID-19. Methods: We subjected post-COVID-19 cholestasis liver samples to routine staining techniques and cytokeratin 7 immunostaining and semi-quantitatively analyzed the portal and parenchymal changes. Results: All ten patients, five men, had a median age of 56, an interquartile range (IQR) of 51–60, and required intensive care unit and mechanical ventilation. The median and IQR liver enzyme concentrations proximal to biopsy were in IU/L: ALP 645 (390–1256); GGT 925 (664–2169); ALT 100 (86–113); AST 87 (68–106); and bilirubin 4 (1–9) mg/dL. Imaging revealed intrahepatic bile duct anomalies and biliary casts. We performed biopsies at a median of 203 (150–249) days after molecular confirmation of infection. We found portal and periportal fibrosis, moderate-to-severe ductular proliferation, and bile duct dystrophy in all patients, while we observed hepatocyte biliary metaplasia in all tested cases. We observed mild-to-severe parenchymal cholestasis and bile plugs in nine and six cases. We also observed mild swelling of the arteriolar endothelial cells in five patients. We observed a thrombus in a small portal vein branch and mild periductal fibrosis in one case each. One patient developed multiple small biliary infarctions. We did not observe ductopenia in any patient. Conclusions: The alterations were like those observed in SSC-CIP; however, pronounced swelling of endothelial cells, necrosis of the vessel walls, and thrombosis in small vessels were notable.