Docetaxel Induced Sclerosing Cholangitis

Excerpt

A 78-year-old gentleman was referred for hepatology consultation. One year prior, he was diagnosed with metastatic high-grade prostate adenocarcinoma. Dual androgen deprivation therapy (ADT) with leuprolide and bicalutamide was started, and he underwent 43 fractions of palliative radiation to the pelvis. Due to evidence of improved survival outcomes with combination ADT and docetaxel in hormonal-sensitive metastatic prostate cancer, chemotherapy was initiated [1]. Prior to initiation of docetaxel, his liver injury tests (LITs) were normal, and computer tomography (CT) of the abdomen and pelvis demonstrated normal liver appearance. Docetaxel was initiated using every 3 week dosing (75 mg/m², total dose = 134 mg), and after administration, the patient developed elevated LITs for the first time: alkaline phosphatase 197 u/l, alanine aminotransferase (ALT) 67 u/l, aspartate aminotransferase (AST) 59 u/l, and total bilirubin 0.9 mg/dl. Patient was asymptomatic, no evidence of abdominal pain, jaundice, or pruritus. He was switched to weekly docetaxel due to side effects (30 mg/m² weekly, total dose = 54 mg); however, LITs elevation continued: alkaline phosphatase 518 u/l, ALT 144 u/l, AST of 90 u/l, and total bilirubin of 0.8 mg/dl. Repeat CT demonstrated new diffuse intrahepatic biliary dilatation with periductal enhancement suggestive of a diffuse cholangitis picture (Fig. 1). Docetaxel was held, and patient was monitored. After 2 months without resolution of abnormal LITs, magnetic resonance imaging (MRI) was pursued, demonstrating continued multifocal narrowing and dilatation of intrahepatic bile ducts, including peripheral bile ducts, with the appearance of sclerosing cholangitis (Fig. 2). An IgG4 level was normal. Liver biopsy 2 months later was performed to determine whether further chemotherapy should be continued, and because of limited evidence that metastatic prostate cancer can simulate sclerosing cholangitis [2]. Biopsy revealed features of subacute bile duct obstruction and stricturing with moderate hepatocanalicular cholestasis, and reactive changes as evidenced by numerous eosinophils. There was biliary-type bridging fibrosis with no architectural distortion or regenerative nodules (Fig. 3). These findings are consistent with a drug-induced inflammation and sclerosing cholangitis. Five months later, imaging portrayed continued evidence of secondary sclerosing cholangitis.

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