What is the definition of acute liver injury?

Definition of Acute Liver Injury

Acute liver injury is defined by any of the following criteria: 1) Alanine aminotransferase (ALT) level ≥5× upper limit of normal (ULN), 2) Alkaline phosphatase (ALP) level ≥2 ULN, or 3) ALT level ≥3× ULN with simultaneous total bilirubin level >2 ULN. 1, 2

Diagnostic Criteria

• The definition of acute liver injury requires meeting at least one of the three threshold criteria for liver enzyme or bilirubin elevation 1
• For patients with abnormal baseline liver tests, the ULN should be replaced by the mean baseline values obtained prior to exposure to the suspect agent 1, 2
• AST can replace ALT when ALT is unavailable for assessment of acute liver injury 1
• Isolated increases in GGT activity are not markers of cellular damage but rather indicate enzyme induction 1

Pattern Classification

• The pattern of liver damage can be classified using the R value, calculated as (ALT/ULN)/(ALP/ULN) 1
• Liver injury is categorized as:
  • Hepatocellular pattern: R ≥5 1, 2
  • Cholestatic pattern: R ≤2 1, 2
  • Mixed pattern: R value >2 and <5 1, 2
• The values used for classification should be those available when liver injury is first recognized, as the pattern may shift over time due to differences in clearance kinetics of ALT and ALP 1

Clinical Presentations

• Acute liver injury can present with various histological patterns, including hepatocellular necrosis, cholestatic/mixed injury, and steatosis 1
• Acute liver injury may progress to acute liver failure if hepatic encephalopathy develops 3, 4
• The risk of progression to poor outcomes (acute liver failure, need for liver transplantation, or death) varies significantly by etiology, with non-acetaminophen causes having a much higher risk (40%) compared to acetaminophen-induced injury (7.2%) 3

Severity Grading

• Severity of acute chemical liver injury can be evaluated using the adapted severity index scale designed for drug-induced liver injury 1
• The progression from acute liver injury to acute liver failure is marked by the development of hepatic encephalopathy 3, 4
• Predictors of progression to poor outcomes include etiology (non-acetaminophen), bilirubin level, INR, and duration of jaundice 3

Important Considerations

• Due to differences in clearance kinetics of ALT and ALP, the injury pattern may shift to a cholestatic/mixed signature over time 1
• In occupational liver diseases, the standard classification used for idiosyncratic drug-induced acute liver failure may not apply due to the direct, massive, and rapid liver damage induced by chemicals 1
• Early recognition of acute liver injury is crucial, as prompt management can prevent progression to acute liver failure 3, 5
• Patients with non-acetaminophen acute liver injury should be considered for early referral to a liver transplant center due to their higher risk of poor outcomes 3, 4