What causes a slight elevation in liver enzymes?

Common Causes of Slight Elevation in Liver Enzymes

The most common causes of mild elevations in liver enzymes are nonalcoholic fatty liver disease (NAFLD) and alcohol-induced liver disease, followed by less common causes including drug-induced liver injury, viral hepatitis (B and C), and hereditary hemochromatosis. 1

Hepatocellular Pattern (Predominant ALT/AST Elevation)

Common Causes

• Nonalcoholic fatty liver disease (NAFLD) - Most common liver disease in developed countries with prevalence of 20-30% in general population, increasing to 70% with obesity and 90% with diabetes 1
• Alcohol-induced liver disease - AST:ALT ratio typically >2, compared to <1 in metabolic-related fatty liver 1
• Medication-related - Prescription drugs (including statins which can cause persistent transaminase elevations in 0.7% of patients), over-the-counter medications, and herbal supplements 2, 3

Less Common Causes

• Viral hepatitis - Acute or chronic hepatitis B, C, A, and E 1
• Hereditary hemochromatosis - Characterized by elevated ferritin and transferrin saturation >45% 1
• Autoimmune hepatitis - Often with positive autoantibodies and elevated IgG 1

Rare Causes

• Wilson disease - Copper metabolism disorder 1
• Alpha-1 antitrypsin deficiency - Genetic disorder affecting liver and lungs 1

Cholestatic Pattern (Predominant ALP/GGT Elevation)

• Biliary obstruction - Including choledocholithiasis, which can sometimes cause markedly elevated transaminases even without primary liver disease 4
• Primary biliary cholangitis - Characterized by positive anti-mitochondrial antibodies 1
• Primary sclerosing cholangitis - Often associated with inflammatory bowel disease 1
• Drug-induced cholestasis - Various medications can cause cholestatic pattern 1, 5

Non-Hepatic Causes of Elevated Liver Enzymes

• Muscle disorders - Can elevate AST (less specific for liver injury) 6, 7
• Thyroid disease - Both hypo- and hyperthyroidism can affect liver enzymes 6
• Hemolysis - Can cause elevated AST 1
• Strenuous exercise - Transient elevation, particularly of AST 1, 6
• Celiac disease - Can present with elevated transaminases 1

Initial Evaluation Approach

History and Risk Assessment

• Obtain detailed alcohol consumption history 6
• Complete medication review including prescription, over-the-counter, and supplements 6, 3
• Assess for metabolic syndrome components (obesity, diabetes, hypertension) 6
• Evaluate for symptoms of chronic liver disease (fatigue, jaundice, pruritus) 6

Laboratory Testing

• Complete liver panel (AST, ALT, alkaline phosphatase, bilirubin, albumin, prothrombin time) 6
• Viral hepatitis serologies (HBsAg, anti-HCV) 1, 6
• Consider autoimmune markers if suspected (ANA, ASMA, IgG) 1
• Thyroid function tests to rule out thyroid disorders 6
• Creatine kinase if muscle disorders suspected 6, 7

Imaging

• Abdominal ultrasound as first-line imaging test (sensitivity 84.8% and specificity 93.6% for moderate to severe hepatic steatosis) 1, 6

Important Considerations

• Normal ALT ranges differ by sex: 29-33 IU/L for males and 19-25 IU/L for females 6
• Up to 30% of mildly elevated transaminases may normalize spontaneously during follow-up 5
• The pattern of enzyme elevation can help guide diagnosis - hepatocellular (predominantly ALT/AST) versus cholestatic (predominantly ALP/GGT) 5, 7
• Patients with previous viral hepatitis should be screened for additional factors of liver damage even if asymptomatic or with normal liver tests 1
• Consider liver biopsy in cases where non-invasive testing is inconclusive, especially with persistent unexplained elevations 1

Management Approach

• For NAFLD: Implement lifestyle modifications including weight loss, exercise, and dietary changes 6
• For alcoholic liver disease: Recommend alcohol cessation and monitor transaminases 6
• For medication-induced injury: Discontinue suspected hepatotoxic medications when possible 6
• For viral hepatitis: Refer for specific management based on viral etiology 6
• For unexplained mild elevations: Repeat liver enzymes in 2-4 weeks 6
• Consider hepatology referral if transaminases remain elevated for ≥6 months or if there is evidence of synthetic dysfunction 6, 7