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

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

Revised: 12 October 2016, last major update June 2016

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

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

Cite this page: Drug / toxin induced hepatitis - General. website. Accessed September 26th, 2017.
Definition / general
  • Drug / toxin reactions can be intrinsic or predictable, where they are dose dependent (e.g. acetaminophen - see topic); or idiosyncratic and unpredictable, where they are dose independent (e.g. isoniazid)
  • The underlying mechanisms include direct / indirect toxicity, aberrant metabolism producing toxic metabolites, and immune-mediated hypersensitivity

  • Risk factors (J Hepatol 2015;63:503)
    • Drug properties (e.g. threshold dosage, lipophilicity, toxic metabolite, oxidative stress, mitochondrial liability, inhibition of hepatobiliary transporters)
    • Host factors (e.g. age, gender, underlying liver or other disease, genetic factors)
    • Drug-host interaction
Diagrams / tables

Images hosted on other servers:

Consensus criteria for terminology in drug-induced liver injury

Overview of drug-induced liver injury patterns

Herbal products with known hepatotoxicity

Clinical features
  • A very wide range of clinical and pathological presentations can result. The time of onset after drug exposure varies from hours to months
  • The clinical manifestations range from asymptomatic deranged liver function to fulminant hepatic failure and death
  • Mimic all forms of acute, chronic, vascular or neoplastic liver diseases that are caused by other etiologies
  • The diagnosis of drug or toxin-induced liver injuries requires clinical, biochemical and pathological correlation
  • 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
Microscopic (histologic) description
  • The morphological patterns can be categorized into:
    • Necroinflammatory injury: Acute hepatic necrosis, acute hepatitis, and granulomatous hepatitis
    • Cholestatic injury: Bland cholestasis, acute cholestatic hepatitis and chronic cholestatic injury
    • Steatosis and steatohepatitis
    • Vascular lesion: Sinusoidal obstruction syndrome, Budd-Chiari syndrome, nodular regenerative hyperplasia, hepatoportal sclerosis, sinusoidal dilatation and peliosis
    • Neoplasm and neoplasm-like lesion
    • Adaptive change
Microscopic (histologic) images

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Resolving hepatitis: Left-
parenchymal infiltrate is
diminished compared to
acute hepatitis; hepatocellular
injury is minimal; prominent
pigment accumulation in
sinusoidal macrophages

Resolving hepatitis: Right-
sinusoidal macrophages are
evident with PAS+ diastase
resistant cytoplasmic contents

Prolonged cholestasis:
persistence of canalicular bile
plugs accompanied by feathery
degeneration of periportal
hepatocytes (cholate stasis)

Microvesicular steatosis:
numerous small lipid
droplets are present
in hepatocyte cytoplasm

Sinusoidal obstruction
syndrome: endothelial injury
in small hepatic venules
leads to luminal occlusion
due to endothelial swelling
and thrombosis, and results in
sinusoidal dilatation and congestion

Peliosis: the hepatic
parenchyma contains
blood-filled cavities that
lack an endothelial lining

Stellate (Ito) cell lipidosis:
fat-laden stellate cells with
multiple lipid vacuoles that
indent the nucleus; Ito cells
are along sinusoids in
space of Disse

Ground-glass hepatocytes:
with cyanamide (used
for alcohol abuse), diazepam,
barbiturates, insulin, IV glucose