Histopathologic Approach to Cholestatic Diseases of the Liver

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Liver biopsy specimens of patients with cholestatic diseases pose a challenge to pathologists since, in most instances, this procedure is performed in a selected group of patients in whom clinical, laboratory, and imaging studies are inconclusive. Proper interpretation of the various histologic features is facilitated by the recognition of the most common patterns, which correlate with a defined group of diseases. Cholestatic disorders are grouped in 2 broad categories: acute and chronic. Four histologic patterns with different clinical implication are recognized within the first category: (1) ductular reaction, (2) pure canalicular cholestasis, (3) cholestasis with intrahepatic bile duct disease, and (4) cholestatic hepatitis. Chronic disorders are recognized by portal-based fibrosis, Mallory-Denk bodies, cholate stasis, accumulation of copper or copper-binding proteins, and biliary-type cirrhosis. Immunohistochemical reactions for cytokeratin 7 help to identify damaged bile ducts, highlight reactive ductules, and, most importantly, provide support for a cholestatic disorder by the staining of periportal hepatocytes (intermediate phenotype). The histologic features of primary biliary cholangitis and primary sclerosing cholangitis are reviewed with special emphasis on overlap syndromes and other entities that enter in the differential diagnosis.

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