Drug-Induced Cholestatic Liver Injury

 Commonly implicated drugs: Anabolic steroids, oral contraceptives, prochlorperazine, thiabendazole, warfarin



• Cholestatic hepatitis: Cholestasis with inflammation and hepatocellular damage
image Macrolide antibiotics (erythromycin), antipsychotics (chlorpromazine), numerous other drugs

• Prolonged cholestasis/ductopenia: Cholestasis > 3 months, bile duct loss
image Antibiotics, antifungals, anticonvulsants, antipsychotics, NSAIDs; rarely oral contraceptives, amiodarone

• Sclerosing duct injury: Fibrosis affecting large bile ducts similar to primary sclerosing cholangitis (PSC)
image 5-fluorodeoxyuridine (intraarterial infusion for metastatic colorectal carcinoma), formaldehyde, and sodium chloride (injected into hydatid cysts)




Top Differential Diagnoses




• Pure cholestasis: Sepsis, shock, benign recurrent intrahepatic cholestasis

• Cholestatic hepatitis: Other causes of hepatitis (viral, autoimmune, Wilson disease)

• Obstructive biliary disease

• Prolonged cholestasis/ductopenia: Primary biliary cholangitis and PSC

image
Obstruction-Like Features
Portal edema, inflammation, and bile ductular reaction in drug-induced liver injury (DILI) may be indistinguishable from obstructive biliary disease on histologic grounds.


image
Cholestatic Hepatitis
Cholestasis is accompanied by hepatitic features evidenced by lobular inflammation and hepatocellular dropout image. This is the most common histologic pattern observed in DILI.

image
Pure Cholestasis
This pattern, also known as bland cholestasis, is characterized by bile in hepatocytes and canaliculi image with no significant hepatocellular injury or inflammation. The portal tracts and interlobular bile ducts are normal and ductular reaction is not present in this pattern.

image
Prolonged Cholestasis
Arteriole without interlobular bile duct indicates bile duct loss image. Swelling of periportal hepatocytes is present image (cholate stasis), a feature of prolonged cholestasis.


TERMINOLOGY


Abbreviations




• Cholestatic drug-induced liver injury (DILI), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC)


ETIOLOGY/PATHOGENESIS


4 General Categories




• Based on symptom duration and histologic pattern of injury


Pure Cholestasis




• Cholestasis with minimal hepatocellular injury

• Commonly implicated drugs: Anabolic steroids, oral contraceptives, prochlorperazine, thiabendazole, warfarin

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Apr 20, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Drug-Induced Cholestatic Liver Injury
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