361.3 🏥 內科專科考前版

361.3.1 Mechanistic Deep Dive

361.3.1.1 Acetaminophen Hepatotoxicity

  • NAPQI metabolite
  • Normally detoxified by glutathione
  • Overdose depletes glutathione
  • NAPQI binds hepatocyte proteins → necrosis
  • NAC replenishes glutathione + binds NAPQI
  • Effective at any time but earlier = better

361.3.1.2 Cerebral Edema Pathophysiology

  • Ammonia → astrocyte swelling (cytotoxic edema)
  • Glutamine accumulation
  • BBB disruption
  • ↑ ICP

361.3.1.3 Coagulopathy Paradox

  • Severe INR elevation but bleeding less common
  • ↓ all factors except VIII (synthesized by endothelium)
  • ↓ anticoagulants (proteins C, S, antithrombin) too
  • Rebalanced
  • Don’t routinely correct unless bleeding or pre-procedure

361.3.2 Recent Trials & Updates

361.3.2.1 NAC for Non-Acetaminophen ALF (Lee 2009)

  • ALF Study Group RCT
  • Improved transplant-free survival in early HE (I-II)
  • Not advanced HE
  • Now standard of care for early non-APAP ALF

361.3.2.2 MELD vs King’s College

  • MELD ≥ 30 also useful predictor
  • May complement King’s

361.3.2.3 Bioartificial Liver

  • Various devices investigated
  • Limited evidence for survival benefit
  • Bridge to transplant in some cases

361.3.2.4 Early LT for Severe Alcoholic Hepatitis

  • See Ch358 — overlaps with ALF
  • Mathurin 2011
  • Strict psychosocial selection

361.3.2.5 Hepatic Auxiliary Transplant

  • Living donor partial liver while native recovers
  • Used for ALF with potential recovery
  • Investigational/specialized centers

361.3.3 High-Yield Specialist Points

361.3.3.1 ICP Monitoring Controversy

  • Coagulopathy risk
  • Some centers use
  • Most rely on clinical + imaging
  • Target ICP < 20-25, CPP > 50-60

361.3.3.2 Mannitol Dose

  • 0.5-1 g/kg IV bolus
  • Repeat as needed
  • Osmolality target < 320

361.3.3.3 Hypertonic Saline

  • 3% NaCl infusion
  • Na target 145-150 mmol/L
  • Alternative to mannitol

361.3.3.4 Therapeutic Hypothermia

  • Some centers
  • 32-34°C
  • Reduces ICP
  • Not standard

361.3.3.5 Phosphate Trend

  • Low phosphate = regenerating liver
  • Good prognostic sign
  • High phosphate = poor recovery

361.3.3.6 Ammonia Levels

  • 200 ÎŒmol/L associated with cerebral edema

  • Trend more useful than absolute
  • Arterial preferred

361.3.3.8 Wilson ALF Markers

  • ALP : bilirubin < 4
  • AST : ALT > 2.2
  • Both criteria + Coombs-negative hemolysis = Wilson likely
  • Almost always need transplant

361.3.3.9 Plasma Exchange

  • High-volume plasmapheresis
  • Larsen 2016 — improved transplant-free survival
  • Mechanism: clearing toxins, inflammatory mediators
  • Increasing use

361.3.3.10 Bridging to Transplant

  • MARS (molecular adsorbent recirculating system)
  • Prometheus
  • Plasma exchange
  • Bioartificial liver
  • All evidence limited

361.3.4 Pearls

  • ALF = encephalopathy + INR ≥ 1.5 + no cirrhosis + < 26 weeks
  • Acetaminophen top in US/UK
  • Hyperacute (< 7 days): cerebral edema common, paradoxically better recovery
  • NAC for acetaminophen AND non-acetaminophen ALF
  • King’s College Criteria for transplant
  • MELD ≥ 30 also indicator
  • Cerebral edema = major cause of death
  • Wilson ALF: ALP : bili < 4, AST : ALT > 2.2, Coombs-negative hemolysis
  • HEV in pregnancy 20% mortality
  • Plasma exchange emerging
  • Transplant: Status 1A; 1-yr 80-85%