Pembrolizumab-related sclerosing cholangitis manifested by a pruned-tree appearance of the bile ducts

An 81-year-old man treated with pembrolizumab (200  mg, triweekly) for non-small-cell lung cancer showed a gradual worsening of his liver enzyme levels despite having no history of liver disease. The pembrolizumab treatments were continued as scheduled until the patient’s liver enzyme levels met the criteria for discontinuation. After the fifth c ycle of pembrolizumab, liver damage became apparent: the alanine aminotransferase level was 419 IU/L, the alkaline phosphatase level was 1987 IU/L and the total bilirubin level was 1.7 mg/dL. Computed tomography showed diffusely thickened extrahepatic bile duct walls (Fig. 1). Endoscopic retrograde cholangiography revealed an extrahepatic bile duct with localized dilatations and a beaded appearance (Fig. 2, arrows), together with irregular discontinuous widening and strictures of the left intrahepatic bile duct (arrowheads). A liver biopsy revealed fibrosis and inflammation accompanied by severe infiltration of the periportal zone (Fig. 3A), in which the inflammatory cells were mostly positive for CD8 (Fig. 3B) but were negative for CD4 (Fig. 3C). A high CD8+/CD4+ cell ratio is a pathological feature of immune-related adverse reactions. The patient did not receive any other drugs that could have caused the cholangitis. After starting oral prednisolone (1  mg/kg/day), the liver enzyme levels gradually improved. Although magnetic resonance cholangiography showed that the extrahepatic bile duct dilation and wall thickness had imp...
Source: Japanese Journal of Clinical Oncology - Category: Cancer & Oncology Source Type: research