Drug-Related Acute Hepatitis

Drug-Related Acute Hepatitis

Sanjay Kakar, MD


2 Chief Mechanisms

  • Intrinsic hepatotoxicity

    • Predictable, dose-dependent hepatocellular damage by drug or its metabolite

      • Industrial, household, or environmental toxins

    • Typical histological feature is necrosis with negligible inflammation

  • Idiosyncratic hepatoxicity

    • Majority of adverse drug reactions fall in this category; antimicrobial and central nervous system drugs are the most common offending agents in children

    • Further classified into metabolic and immunological categories

      • Metabolic: Drug is metabolized into toxic metabolite in predisposed individuals

      • Immunological: “Drug allergy” or hypersensitivity following sensitization to drug

    • Typical histological feature is inflammation-predominant liver injury


  • Important but often overlooked cause of hepatotoxicity

  • Not regulated by Food and Drug Administration and hence not subject to rigorous testing

  • Nearly 20% of American adults have used herbal remedies, and > 5 billion dollars are spent on these annually

  • Contaminants in herbal supplements, including heavy metals such as arsenic, cadmium, lead, or mercury, can also lead to liver toxicity



  • Clinical patterns of injury classified based on pattern of liver enzyme abnormalities

    • Hepatitic

      • Acute hepatitis with autoimmune markers may mimic autoimmune hepatitis (AIH)

      • May have features of hypersensitivity like rash, arthralgia, and peripheral eosinophilia

      • Progression to chronic hepatitis with fibrosis and even cirrhosis can occur

    • Cholestatic

    • Mixed

  • Classified into acute or chronic based on duration of injury

  • Establishing drug as causative agent is key

    • Temporal profile of onset of liver dysfunction is crucial

    • Liver toxicity may manifest weeks or months after drug ingestion and even after drug has been stopped

    • Systematic literature search for each drug that patient has been taking is necessary

    • If observed and reported patterns of clinical and histological injury are similar, case for drug-induced liver injury (DILI) is strengthened

    • Rechallenge can help confirm drug etiology but is rarely done

Laboratory Tests

  • Measurement of serum levels of drug or its metabolite can be helpful in diagnosis (e.g., acetaminophen toxicity)

  • Antinuclear &/or anti-smooth muscle antibodies may be present

  • Transaminase elevations may be marked


Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Drug-Related Acute Hepatitis
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