Drug induced liver injury classification

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rachita Navara, M.D. [2]

Overview

Drug induced liver injury may be classified into multiple subtypes based on clinical presentation, mechanism, or histologic findings.[1]

Classification

Drug induced liver injury may be classified into multiple subtypes based on clinical presentation, mechanism, or histologic findings.

Clinical presentation:

Hepatocellular injury

  • Elevation of serum transaminases ≥ 2-5 times the upper limit of normal
  • May have hyperbilirubinemia
  • May have abnormal synthetic function tests (e.g. International Normalized Ratio, albumin)

Cholestatic injury

  • Elevation of alkaline phosphatase ≥ 3 times the upper limit of normal
  • May have hyperbilirubinemia
  • May have abnormal synthetic function tests (e.g. International Normalized Ratio, albumin)

Mixed injury

  • Both alkaline phosphatase and transaminases are elevated in roughly equal proportion, and/or an alanine aminotransferase to alkaline phosphatase ratio between 2-5

Mechanism:

Dose-dependent hepatotoxicity

  • e.g. Acetaminophen-induced centrilobular necrosis

Idiosyncratic hepatotoxicity

  • e.g. Stimulation of immune reponse by biologic agents, independent of dose, akin to drug hypersensitivity
  • e.g. Altered host genes involved in drug metabolism

Histologic findings:

Histologic findings may be further subclassified into:

References

  1. Fisher K, Vuppalanchi R, Saxena R (2015). "Drug-Induced Liver Injury". Arch Pathol Lab Med. 139 (7): 876–87. doi:10.5858/arpa.2014-0214-RA. PMID 26125428.