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Acute Hepatocellular Injury (”Transaminosis” “Transaminitis”)

One Pager ✍️

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Definitions 📚

  • Acute Hepatocellular Injury (“transaminosis, transaminitis”) 🟤 : ↑ AST & ALT (i.e. doesn’t imply liver function)

  • Acute Liver Injury (ALI) 🟤 : ↑ AST & ALT without liver failure (i.e. normal INR, no hepatic encephalopathy)

  • Acute Liver Failure (ALF) 💀: ALI + liver failure (i.e. coagulopathy, hepatic encephalopathy)

Filters 🔍

Mild vs. Severe

  • “Severe” Acute Hepatocellular Injury: the **asterisks** in the one-pager above denote those disorders that can lead to severely elevated AST & ALT (e.g. > 1,000 U/L). This is an important DDx filter as only a narrow list of diseases can lead to elevations within this range

  • Filtering the Filter: of the **asterisk’d** diseases, those diseases that lead to hepatocyte release of AST & ALT via necrosis lead to a much more impressive rise (e.g. > 2,000 U/L) than those diseases that lead to release via apoptosis. Necrosis is generally related to ischemia (e.g. ischemic hepatitis, metastatic liver crisis), toxins (e.g. DILI), & profound inflammation (e.g. viral hepatitis, autoimmune hepatitis). Apoptosis is seen in metabolic disorders (e.g. Wilson’s crisis): the severity of AST & ALT elevation in these disorders is generally lesser (e.g. < 2,000 U/L)

AST:ALT > 2

  • This frequently cited lab pattern in the acute setting usually conjures extrahepatic hypotheses since AST is found inside numerous other cells (i.e. skeletal muscle, myocardium, RBCs), with rhabdomyolysis being the most common extrahepatic source of AST > ALT in clinical practice. (AST as a signal for MI & hemolysis is generally only seen in severe presentations of MI & hemolysis, & thus is generally easily recognizable.) For this reason, the highest-yield screening test for extrahepatic AST is the CK.
  • After consideration of extrahepatic sources of AST, the AST:ALT ratio of >2 then implies several unique hepatic diseases, noted by mechanism below:

Acute

  • Extrahepatic
    • Rhabdomyolysis (↑ CK)
    • Myocardial infarction (↑ troponin)
    • Massive hemolysis (↓ haptoglobin)
    • Bone marrow precursors (e.g. myelophthisis, MDS, HLH, necrosis)

  • Hepatic
    • Mild-Moderate
      • Alcohol-associated hepatitis (mitochondrial AST release, ↓ ALT synth.)
    • Moderate-Severe
      • Ischemic hepatitis* & hepatic infarction (↓ ATP → mitochondrial failure)
      • Toxic liver injury (direct mitochondrial membrane disruption)
      • Glycogenic hepatopathy (organeller crowding → mitochondrial leak)
      • Metastatic liver crisis (occult sinusoidal compression e.g. SCLC, breast)

      ⚪ Of the shock states, cardiogenic shock is the most common culprit, as ↑ venous hepatic outflow pressure is generally required for frank ischemia of hepatocytes, which are protected by their dual blood supply (i.e. portal vein ⊕ hepatic artery)

Chronic

  • “MacroAST” disease

Visceral crisis of malignancy (AST > ALT, serially rising INR)
Visceral crisis of malignancy (AST > ALT, serially rising INR)

References 📚