What is Transaminitis?
Transaminitis is a term used to describe elevated serum levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST), indicating hepatocellular inflammation or injury. 1, 2
Definition and Terminology
Transaminitis specifically refers to inflammatory liver processes characterized by elevated ALT and AST levels, distinguishing it from "abnormal liver function tests" which denote loss of synthetic function (measured by albumin and prothrombin time). 2
The term should be reserved for describing inflammatory conditions rather than all causes of elevated liver enzymes, as transaminases are sensitive markers of tissue damage but not always specific to hepatotoxicity. 3
Grading System
Transaminitis severity is classified based on the degree of enzyme elevation: 1
- Grade 1: AST/ALT > upper limit of normal (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
Clinical Significance
Transaminitis is typically asymptomatic and detected on routine blood monitoring, though patients may present with fatigue, nausea, jaundice, or other symptoms depending on the underlying cause. 4
The presence of elevated ALT is associated with increased liver-related mortality, making it an important marker for identifying patients requiring further evaluation. 5
ALT is more specific for liver injury than AST, as AST can be elevated in cardiac, skeletal muscle, kidney, and red blood cell disorders. 6
Common Etiologies
The most frequent causes requiring investigation include: 4, 6
- Non-alcoholic fatty liver disease (NAFLD) - the most common cause of mild transaminitis in developed countries
- Alcoholic liver disease - requires detailed alcohol consumption history
- Viral hepatitis (A, B, C, E) - necessitates serological testing 4
- Drug-induced liver injury - requires comprehensive medication and supplement review 1, 7
- Autoimmune hepatitis - presents with hyperglobulinemia and positive autoantibodies 4
- Metabolic/genetic disorders - including hemochromatosis, Wilson's disease, and alpha-1 antitrypsin deficiency 4, 5
Important Caveats
Normal transaminase levels do not rule out significant liver disease, as the majority of NAFLD patients have normal transaminases, and some patients with cirrhosis may present with normal values. 4
Transaminase elevation can occur without true hepatotoxicity, particularly with drugs that modify gluconeogenesis (such as α-glucosidase inhibitors and fibrates), representing "pharmacology-related elevation" rather than drug-induced liver injury. 3
The traditional upper limit of "normal" ALT underestimates liver disease prevalence; revised thresholds are 30 U/L for men and 19 U/L for women. 4