What is Transaminitis?
Transaminitis is a clinical term describing elevated serum levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which indicate hepatocellular injury rather than actual measurement of liver function. 1
Definition and Terminology
- The term "transaminitis" or "abnormal liver enzymes" specifically refers to inflammatory processes characterized by elevated ALT and AST levels, along with alkaline phosphatase 1
- These enzymes leak from liver cells into serum when hepatocytic injury and necrosis occur due to diffuse hepatic infiltration (fat, copper, or iron), acute hepatitis, toxic injury, or ischemic damage 2
- It is important to distinguish transaminitis from "abnormal liver function tests," which specifically denote loss of synthetic functions measured by serum albumin and prothrombin time 1
Normal Values and Grading
- Normal ALT levels are 29 to 33 IU/L in men and 19 to 25 IU/L in women, though some sources suggest the upper limit of normal should be lowered to 30 U/L for men and 19 U/L for women 2
- Transaminitis severity is graded as follows: 3
- Grade 1: AST/ALT > upper normal limit (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
Enzyme Specificity
- ALT elevations are more specific for liver injury because ALT is concentrated primarily in the liver with low concentrations in skeletal muscle and kidney 2
- AST is less specific as it can be elevated due to disorders involving the heart, skeletal muscle, kidneys, brain, and red blood cells 2
- Both transaminases are key enzymes in gluconeogenesis and glycolysis pathways, and their activities can be altered by nutritional or hormonal factors even without true hepatotoxicity 4
Common Causes
The most common cause of mild transaminitis in developed countries is non-alcoholic fatty liver disease (NAFLD), which is strongly associated with metabolic syndrome components including obesity, type 2 diabetes, hypertension, and hypercholesterolemia 3
Other important causes include: 3
- Drug-induced liver injury (DILI) from medications such as methotrexate, NSAIDs, statins, anticonvulsants, and antiarrhythmics
- Viral hepatitis (hepatitis A, B, C, and E)
- Autoimmune hepatitis
- Alcohol-related liver disease
- Hemochromatosis and Wilson's disease
Important Clinical Pitfalls
- The majority of NAFLD patients have normal transaminases, and normal transaminase levels do not rule out histologically advanced liver disease 2
- Transaminase elevations can occur from extrahepatic causes, particularly muscle injury from vigorous exercise, which can cause tremendously elevated levels in otherwise healthy individuals 5
- Some medications like α-glucosidase inhibitors and fibrates can cause "pharmacology-related elevation" of transaminases through modification of gluconeogenesis, which may not represent true drug-induced liver injury 4
- Statin-induced transaminitis (>3× ULN) is infrequent, often resolves with dose reduction, and statins are not contraindicated in chronic stable liver disease like NAFLD 3