Drug-Induced Liver Injury and Acute Liver Failure

• Audio chapter
  Single-voice audio, listen on the commute.
• ABIM-format MCQs
  5-option vignettes with full wrong-answer teaching.
• Study guide
  Tables, decision trees, primary sources.
• AI tutor
  Chapter-grounded, answers the question you're stuck on.

What this chapter covers

• Section 19.1: DILI epidemiology and risk factors

  Drug-induced liver injury belongs in the differential of any new liver test abnormality, because essentially any drug, herbal product, or dietary supplement can produce essentially any pattern of injury.

• Section 19.2: CYP interactions and metabolic activation

  DILI is fundamentally a problem of reactive metabolite generation, which explains why a particular drug becomes hepatotoxic in a particular host.

• Section 19.3: Hy's Law and severity

  Hy's Law identifies an early biochemical signature of serious DILI before fulminant failure becomes obvious.

• Section 19.4: Histology patterns by drug class

  DILI histology falls into recognizable patterns, and the pattern often points to the drug class.

• Section 19.5: Acetaminophen toxicity and NAC

  Acetaminophen toxicity is the prototypical intrinsic DILI, the leading cause of acute liver failure in the United States and the United Kingdom.

• Section 19.6: ALF definition, etiologies, and ALFSG distribution

  Acute liver failure is the small but lethal entity defined by the rapid loss of hepatic synthetic and detoxifying function in a previously healthy liver, and management depends on applying the definition correctly.

• Section 19.7: Wilsonian and HSV ALF

  Wilsonian ALF and HSV ALF need specific recognition, because both have characteristic findings and specific measures that should be started before confirmation.

• Section 19.8: King's College Criteria and ALF triage

  The King's College Criteria are the prognostic scoring tools developed at King's College Hospital in London that identify ALF patients who are unlikely to recover without transplantation.

Podcast episodes

1. 01

   Drug Injury and Liver Failure: Causes and Patterns

   Drug injury happens when a drug's reactive intermediate outruns the liver's ability to neutralize it, and that one idea ties the episode together. It starts with a woman on nitrofurantoin, where Hy's law, the R ratio, and RUCAM set severity, pattern, and causality, and where autoimmune-like injury is told apart from true autoimmune hepatitis. Supplements and HLA testing before abacavir follow, then the metabolic mechanism seen with isoniazid and acetaminophen, and the separate rules for valproate, methotrexate, statins, and amiodarone. Biopsy patterns come next, from cholestasis after amoxicillin-clavulanate to DRESS, granulomas, steatosis, and sinusoidal obstruction. The episode ends with acetaminophen: toxic thresholds, the limits of the nomogram, and N-acetylcysteine dosing.

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2. 02

   Drug Injury and Liver Failure: Acute Liver Failure

   Acute liver failure is a loss of liver function in a previously healthy liver, and the organizing idea is that the cause and the timing drive every decision. The episode defines it with four criteria, separates it from acute-on-chronic failure, and explains why only acute liver failure swells the brain. It then covers causes and which recover alone, followed by ICU management of glucose, coagulopathy, infection, and cerebral edema. Three treatments that start before confirmation come next: fulminant Wilson disease, herpes simplex hepatitis, and N-acetylcysteine for non-acetaminophen failure. It closes with early transfer, the two King's College versions, Status one-A listing, and contraindications.

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Key topics

• ·Three kinds of drug injury and risk factors
• ·Hy's law and the R ratio
• ·RUCAM causality scoring
• ·Drug-induced autoimmune-like hepatitis
• ·Supplements and HLA-B 5701 testing
• ·Reactive metabolites and isoniazid
• ·Valproate, methotrexate, statins, and amiodarone
• ·Biopsy patterns of drug injury
• ·Acetaminophen toxicity and the nomogram
• ·N-acetylcysteine dosing
• ·Four criteria for acute liver failure
• ·Acute-on-chronic failure and cerebral edema
• ·Encephalopathy grades
• ·Causes and spontaneous recovery
• ·ICU management of complications
• ·Intracranial hypertension management
• ·Fulminant Wilson disease
• ·Herpes simplex hepatitis
• ·N-acetylcysteine without acetaminophen
• ·Transfer, King's College criteria, and Status one-A listing