Fatal cholestatic liver injury following roxadustat administration in hemodialysis patients： A case series of four patients with autopsy findings

Abstract

Roxadustat, a hypoxia‒inducible factor prolyl hydroxylase inhibitor, is widely used to treat patients with renal anemia. We report four hemodialysis patients who developed fatal jaundice during roxadustat treatment. In all cases, direct bilirubin‒dominant jaundice manifested following dose escalation to 150 or 200 mg (three times weekly). Biliary obstruction and other primary liver diseases were ruled out, leading to a suspicion of drug‒induced liver injury (DILI). Although the elevation of hepatobiliary enzymes was disproportionately mild, the clinical presentation suggested a cholestatic pattern of liver injury. Autopsy findings in one case revealed a mixed pattern of DILI characterized by both hepatocellular necrosis and cholestasis. Correlation with the clinical course suggested that prolonged cholestasis may have induced secondary hepatocellular damage. Although all patients were classified as Child‒Pugh class A at the initiation of treatment, three had pre‒existing morphological liver abnormalities on prior imaging studies and elevated FIB‒4 index scores. When administering roxadustat, clinicians should pay close attention to any history of liver dysfunction or morphological abnormalities. Careful monitoring of the liver function, including bilirubin levels, is essential, especially during high‒dose therapy, to ensure early detection of clinical signs and prevent fatal outcomes.