What is Transaminitis?
Transaminitis is defined as elevated serum levels of the aminotransferases (transaminases) alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which serve as sensitive markers of hepatocellular injury and disturbed cell membrane permeability. 1, 2, 3
Clinical Definition and Terminology
The term "transaminitis" specifically describes inflammatory processes characterized by elevated ALT and AST levels, and should be reserved for conditions involving hepatocellular injury rather than cholestatic patterns. 3
This terminology is distinct from "abnormal liver function tests," which specifically denotes loss of synthetic functions evaluated by serum albumin and prothrombin time, not just enzyme elevation. 3
Transaminases are key enzymes in gluconeogenesis and glycolysis pathways that exist in many organs and tissues with high metabolic activity, not exclusively in the liver. 4
Grading System
Transaminitis severity is classified using a standardized grading system based on multiples of the upper limit of normal (ULN): 1
- Grade 1: AST/ALT >ULN to 3.0× ULN
- Grade 2: AST/ALT >3.0 to 5.0× ULN
- Grade 3: AST/ALT >5.0 to 20× ULN
- Grade 4: AST/ALT >20× ULN
Normal Reference Ranges
Normal ALT levels range from 29-33 IU/L in males and 19-25 IU/L in females, with values varying by laboratory and population. 2
AST is less liver-specific than ALT, as it is found in other organs including heart and skeletal muscle, making ALT elevation more specific for hepatocellular injury. 5
Diagnostic Significance
The AST:ALT ratio provides important diagnostic clues: an AST:ALT ratio <1 suggests non-alcoholic fatty liver disease (NAFLD), while an AST:ALT ratio >1 may indicate advanced fibrosis, cirrhosis, or alcoholic liver disease. 1, 6
Elevated ALT is associated with increased liver-related mortality, making any persistent elevation clinically significant even when transaminases fluctuate between normal and abnormal ranges. 2, 6
Important Clinical Caveats
Transaminase elevation is not always accompanied by hepatotoxicity—drugs that modify gluconeogenesis (such as α-glucosidase inhibitors and fibrates) can cause "pharmacology-related elevation" without true liver injury. 4
Approximately 50% of patients with chronic liver disease can have normal transaminases despite ongoing hepatic injury, and transaminase levels correlate poorly with necroinflammatory and fibrosis scores. 6
Transaminases can be elevated from non-hepatic sources, including skeletal muscle disorders (myopathies, rhabdomyolysis, vigorous exercise) and cardiac conditions (congestive heart failure causing hepatic congestion). 1