Acute Hepatocellular Injury

Principles ❗

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

• Acute Liver Injury 🟤 : acute transaminosis without liver failure (i.e. normal INR, no encephalopathy)

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

• Severe transaminosis: the asterisks in the one-pager above denote those disorders that can lead to severely elevated transaminases (e.g. > 1,000 U/L)

• 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), & 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)

• This frequently cited lab pattern in the acute setting usually conjures extrahepatic sources of elevated transaminases since AST is found inside other cells (i.e. skeletal muscle, myocardium, RBCs). However, this pattern is a consequence of various hepatic diseases of varying tempos:

References 📚

• DILI histopathology

• "The Kiss of Death" (NEJM HSV case)

• Macro-AST: A Normal Explanation for Abnormal LFTs

• 1/29/2025 VMR (D. Serantes)