From the Guidelines
Acute rises in AST and ALT are primarily caused by hepatocellular injury, with common causes including fatty liver disease, acute or chronic viral hepatitis, and medications/toxins, as evidenced by the most recent study 1. The causes of acute rises in AST and ALT can be categorized into hepatocellular and non-hepatic causes.
- Hepatocellular causes include:
- Fatty liver disease, which is the most common liver disease in first-world countries, with a prevalence of 20% to 30% in the general population, increasing to 70% with obesity and 90% with diabetes mellitus 1
- Acute or chronic viral hepatitis, such as hepatitis B and C
- Medications/toxins, such as acetaminophen and certain antibiotics
- Autoimmune hepatitis, ischemic hepatitis, and Wilson disease
- Non-hepatic causes, which should be considered if the aminotransferase rise is predominantly AST, include:
- Hemolysis
- Myopathy
- Thyroid disease
- Exercise The pattern and degree of elevation can provide clues to the underlying cause, with very high levels (>1000 IU/L) suggesting acute viral hepatitis, drug toxicity, or ischemic injury, while more modest elevations may indicate chronic liver disease 1. When AST is higher than ALT, alcohol-related injury is often suspected, whereas ALT elevation exceeding AST typically occurs in viral hepatitis and drug-induced liver injury, as supported by a study on alcoholic liver disease 1. However, the most recent and highest-quality study 1 prioritizes hepatocellular injury as the primary cause of acute rises in AST and ALT, emphasizing the importance of prompt identification and intervention to prevent permanent liver damage.
From the Research
Causes of Acute Rise in AST and ALT
- Hepatocellular damage, as indicated by elevated serum levels of transaminases (AST and ALT) 2
- Ischemic hepatitis, acute viral hepatitis, and drug-induced liver injury (DILI) are common causes of severe acute liver injury with ALT and/or AST levels ≥1000 IU/L 3
- Non-hepatic causes of raised ALT and AST include:
- Polymyositis
- Acute muscle injury
- Acute myocardial infarction
- Hypothyroidism 4
- Extrahepatic sources, such as:
- Thyroid disorders
- Celiac sprue
- Hemolysis
- Muscle disorders 5
- Chronic alcohol consumption, drugs, non-alcoholic steatohepatitis (NASH), and chronic viral hepatitis are common causes associated with raised ALT and AST 4
- Alcoholic liver disease and nonalcoholic fatty liver disease are the most common causes of elevated transaminase levels 5
Evaluation and Diagnosis
- The initial evaluation should include an assessment for metabolic syndrome and insulin resistance 5
- A complete blood count with platelets, measurement of serum albumin, iron, total iron-binding capacity, and ferritin, and hepatitis C antibody and hepatitis B surface antigen testing should be performed 5
- The nonalcoholic fatty liver disease fibrosis score and the alcoholic liver disease/nonalcoholic fatty liver disease index can be helpful in the evaluation of mildly elevated transaminase levels 5