Docetaxel Induced Sclerosing Cholangitis

Abstract

A 78 year-old man with history of high-grade metastatic prostate cancer was referred to hepatology for abnormal liver function tests. Prior to evaluation, tumor had been surgically removed, he was started on dual androgen deprivation therapy with leuprolide and bicalutamide, and underwent 43 fractions of palliative radiation. Then single agent docetaxel treatment was initiated. Labs drawn with second dosing of the agent, a month after first dose, demonstrated elevated liver injury tests (LITs): alkaline phosphatase 859 u/l, alanine aminotransferase 87 u/l, aspartate aminotransferase 121 u/l, total bilirubin 1.1 mg/dL, which had never been abnormal previously. Patient was asymptomatic, and CT of the abdomen and pelvis prior to initial docetaxel dosing when LFTs were normal, demonstrated normal liver appearance. After abnormal LITs repeat CT demonstrated new diffuse intrahepatic biliary dilatation with periductal enhancement suggestive of a diffuse cholangitis picture. Docetaxel was held, and patient was followed for two additional months without resolution of abnormal LITs, which prompted magnetic resonance imaging (MRI). MRI demonstrated continued multifocal narrowing and dilatation of intrahepatic bile ducts, including peripheral bile ducts, with the appearance of sclerosing cholangitis. IgG4 level was normal. Patient underwent liver biopsy two months later when LITs continued to be abnormal. Biopsy revealed 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 and Batts-Ludwig fibrosis stage 2/4, consistent with drug-induced inflammation and sclerosing cholangitis. Additional staining with CK7 and copper stain also supported the diagnosis. Docetaxel is an anti-mitotic agent with extensive liver metabolism. Known adverse effects can include hepatotoxicity in the form of elevated LITs, which was the initial presentation of this patient. However, to our knowledge, it has never been associated with inducing secondary sclerosing cholangitis. Given the correlation of timing and direct comparison imaging showing the distinct changes of bile ducts associated with drug administration and LIT changes, without other cause being identified, it appears this patient's sclerosing cholangitis is secondary and likely caused by docetaxel.Figure 1Figure 2