What is Transaminitis?
Transaminitis is a term used to describe elevated levels of liver enzymes—specifically alanine aminotransferase (ALT) and aspartate aminotransferase (AST)—in the blood, indicating hepatocellular injury or inflammation. 1
Definition and Terminology
The term "transaminitis" or "abnormal liver enzymes" specifically refers to inflammatory processes characterized by elevated ALT, AST, and sometimes alkaline phosphatase, distinguishing it from "abnormal liver function tests" which denote loss of synthetic functions measured by serum albumin and prothrombin time 1
Transaminases are key enzymes in the gluconeogenesis and glycolysis pathways that exist in many organs and tissues with high metabolic activity, though ALT is primarily concentrated in the liver making it more specific for hepatocellular injury 2, 3
Severity Grading
Transaminitis is classified based on the degree of enzyme elevation relative to the upper limit of normal (ULN): 4
- 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 differ by sex: 29-33 IU/L for males and 19-25 IU/L for females 5, 3
These sex-specific ranges are critical for accurate interpretation, as elevations in women may be more clinically significant given their lower baseline values 5
Clinical Significance
ALT is more liver-specific than AST because it has minimal presence in other tissues like skeletal muscle and kidney, making ALT elevations more indicative of true hepatocellular damage 5, 3
AST can be elevated in non-hepatic conditions including cardiac injury, skeletal muscle disorders, kidney disease, and red blood cell disorders, reducing its specificity for liver injury 5
Multiple studies have demonstrated that elevated ALT is associated with increased liver-related mortality, underscoring the importance of proper evaluation 3
Common Causes
The most frequent etiologies of transaminitis include: 4
- Non-alcoholic fatty liver disease (NAFLD): The leading cause of mild transaminitis in developed countries, strongly associated with metabolic syndrome components
- Drug-induced liver injury (DILI): Caused by hepatotoxic medications including methotrexate, NSAIDs, statins, anticonvulsants, and herbal supplements
- Viral hepatitis: Including hepatitis A, B, C, and E
- Autoimmune hepatitis: Presents with persistently elevated transaminases, hyperglobulinemia, and positive autoantibodies
- Alcohol-related liver disease: Even moderate consumption can cause enzyme elevations
Important Clinical Pearls
Not all transaminase elevations indicate liver injury—pharmacology-related elevations can occur with drugs that modify gluconeogenesis (like α-glucosidase inhibitors and fibrates) without causing true hepatotoxicity 2
Transaminitis can be asymptomatic and discovered incidentally, or present with symptoms including fatigue, nausea, vomiting, right upper quadrant pain, and jaundice 4, 6
The AST:ALT ratio provides diagnostic clues: a ratio <1 suggests NAFLD or viral hepatitis, while a ratio >1 may indicate alcoholic liver disease or advanced fibrosis 4
Mild elevations (<3× ULN) without bilirubin elevation are often non-specific and may be related to NAFLD, dietary changes, or vigorous exercise rather than clinically significant liver injury 4