Introduction: Liver chemistry abnormalities are a frequent manifestation of coronavirus disease 2019 (COVID-19) but are usually transient and resolve with disease resolution. Methods: We describe the clinical course and histologic features of 3 adults who developed prolonged and severe cholestasis during recovery from critical cardiopulmonary COVID-19. Results: These patients had clinical and histologic features similar to secondary sclerosing cholangitis of the critically ill patient, but with unique histologic features including severe cholangiocyte injury and intrahepatic microangiopathy suggestive of direct hepatic injury from COVID-19. DISCUSSION: We believe that these cases constitute a novel severe post–COVID-19 cholangiopathy with potential for long-term hepatic morbidity.

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