Liver and intrahepatic bile ducts-nontumor
Hepatitis - noninfectious
Drug / toxin induced hepatitis - Other examples

Author: Anthony W.H. Chan, BMedSc, MBChB, FRCPA, FHKAM (see Authors page)

Revised: 27 July 2016, last major update July 2016

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Drug induced hepatitis [title] OR Toxin induced hepatitis [title]

Cite this page: Drug / toxin induced hepatitis - other examples. PathologyOutlines.com website. http://pathologyoutlines.com/topic/liverdrugtoxinexamples.html. Accessed January 21st, 2017.
Definition / General
  • Drug / toxin reactions can present with a wide range of clinical and pathological manifestations, and mimic various acute, chronic, vascular or neoplastic liver diseases
  • The website, LiverTox, which is produced by NLM (National Library of Medicine) and NIDDK (National Institute of Diabetes and Digestive and Kidney Disease), provides up to date, accurate and easily accessed information on drug induced liver injury

  • Anabolic steroids:
    • Elevation of liver enzymes, cholestatic jaundice, liver tumors (benign and malignant), peliosis hepatitis

  • Chlorpromazine:
    • Slow metabolizers have cholestasis and jaundice 1 - 5 weeks after treatment
    • Good prognosis

  • Halothane:
    • Rare, fatal immune mediated hepatitis

  • Isoniazid:
    • Hepatocellular inflammation

  • Methotrexate:
    • Related to duration of therapy

  • Ramipril:
    • An inhibitor of angiotensin converting enzyme
    • Case reports of hepatitis in 3 men ages 51 - 59 years (Arch Pathol Lab Med 2003;127:1493)
    • May cause prolonged cholestatic hepatitis and biliary cirrhosis; other ACE inhibitors rarely cause cholestasis

  • Terbinafine:
    • Antifungal drug for onychomycosis and chronic subcutaneous mycosis
    • May cause persistent cholestasis (even after drug withdrawal), liver failure and death
    • Histologic changes resemble acute cellular rejection (Hum Pathol 2003;34:187)
Case Reports
Gross Images

Images hosted on other servers:

Halothane: soft friable liver
due to massive necrosis

Micro Description
    Typical examples:

  • Carbon tetrachloride:
    • Centrilobular necrosis

  • Chlorpromazine:
    • Cytoplasmic and canalicular cholestasis, portal inflammation with eosinophils
    • Minimal necrosis

  • Cholestatic injury:
    • Bland cholestasis, due to oral contraceptives
    • Acute cholestatic hepatitis, due to amoxicillin / clavulanate (Gut 1992;33:368)
    • Chronic cholestatic injury, due to chlorpromazine (Hepatology 1994;20:1437)

  • Methotrexate:
    • Steatosis, ballooning degeneration and necrosis, cholestasis, portal inflammation, progressive fibrosis, cirrhosis

  • Necroinflammatory injury:
  • Neoplasm and mimics
  • Oral contraceptives:
    • Pure canalicular cholestasis with normal portal tracts

  • Phenothiazines:
    • Neutrophils, cholestatic hepatitis

  • Phenylbutazone:
    • Epithelioid granulomas

  • Phenytoin (Dilantin):
    • Multiple histiocytic granulomas
    • Also cholestasis, multifocal necrosis, lymphocyte beading in sinusoids (similar to infectious mononucleosis)

  • Ramipril:
    • Cholestasis, duct necrosis, extravasation of bile, ductular proliferation, portal inflammation

  • Steatosis and steatohepatitis
  • Sulfa drugs:
    • Granulomas, often epithelioid

  • Terbinafine:
    • Marked centrilobular cholestasis, severe bile duct damage

  • Tetracycline:
    • Microvesicular steatosis

  • Vascular lesion
Micro Images

Images hosted on other servers:

Anabolic steroid
induced pure cholestasis:
Prominent bile plugs are
present in hepatocytes
and canaliculi without
inflammation or
hepatocellular damage

Atorvastatin induced
acute hepatitis: mixed
parenchymal inflammation
with lymphocytes,
plasmahistiocytic cells,
neutrophils; no bile duct
damage or fibrosis

Cresol: focal hepatocyte
dropout and regeneration

Erythromycin related cholestatic
hepatitis: features similar to
acute hepatitis, plus bile plugs in
hepatocytes and canaliculi



Methotrexate
toxicity: prominent
macrovesicular steatosis
and periportal fibrosis

Methotrexate: advanced
lesion with ballooning
degeneration and necrosis,
cholestasis, early fibrosis

Phenytoin (Dilantin):
cytoplasmic cholestasis
and lymphocyte beading
in sinusoids

Tetracycline: minocycline induced
autoimmune hepatitis: marked
necroinflammatory activity with
numerous plasma cells



Phenytoin (Dilantin): histiocytic granuloma

Ramipril: necrotic bile ducts

Sulfa drugs: granuloma

Microvesicular steatosis