Is an elevated Aspartate Aminotransferase (AST) of 70 with a normal Alanine Aminotransferase (ALT) in a patient with well-controlled Diabetes Mellitus (DM) and a known history of Non-Alcoholic Fatty Liver Disease (NAFLD) something to work up?

Evaluation of Elevated AST with Normal ALT in a Patient with NAFLD and Well-Controlled Diabetes

An elevated AST of 70 with normal ALT in a patient with well-controlled diabetes and known NAFLD warrants further workup to rule out non-hepatic causes of isolated AST elevation and assess for advanced liver disease.

Understanding AST/ALT Patterns in NAFLD

In NAFLD, the typical pattern is a mild elevation of both AST and ALT, with an AST:ALT ratio <1 1. When the AST:ALT ratio is >1, especially with normal ALT, this is atypical for early NAFLD and requires investigation for:

1. Advanced NAFLD/NASH: In later stages of NAFLD, the AST:ALT ratio may reverse (>1) 1
2. Non-hepatic causes of AST elevation: Hemolysis, myopathy, thyroid disease, or exercise 1

Recommended Diagnostic Approach

Initial Evaluation

• Complete liver chemistry panel (if not already done)
• Complete blood count with platelets
• International normalized ratio (INR)
• Creatinine
• Abdominal ultrasound

Rule Out Non-Hepatic Causes of Isolated AST Elevation

• Check creatine kinase (CK) to rule out muscle injury
• Evaluate for hemolysis (LDH, haptoglobin, reticulocyte count)
• Thyroid function tests
• Review recent physical activity/exercise patterns

Assess for Other Liver Diseases

• Hepatitis B serology (HBsAg, anti-HBc)
• Hepatitis C antibody with reflex RNA testing if positive
• Autoimmune markers (ANA, SMA, IgG levels) if suspected
• Review medications for potential hepatotoxicity

Imaging

• Abdominal ultrasound is the first-line imaging modality to assess liver morphology, presence of steatosis, and signs of advanced disease 1
• Ultrasound can diagnose hepatic lipid content >33% with 84.8% sensitivity and 93.6% specificity 1

Interpretation of Findings

Key Considerations

• Normal ALT does not exclude NASH or advanced fibrosis 1, 2
• Studies show that 42% of patients with ALT below 0.5 times the upper limit of normal can still have NASH, and 16% may have significant fibrosis 2
• AST:ALT ratio >1 may indicate more advanced disease in NAFLD patients 1

Red Flags Requiring Hepatology Referral

• Persistent elevation of AST despite intervention
• Development of other abnormal liver tests
• Signs of hepatic decompensation
• Conflicting clinical, laboratory, and imaging findings

Management Approach

1. Address modifiable risk factors:

   • Optimize diabetes management
   • Weight loss if overweight/obese
   • Mediterranean diet
   • Regular exercise

2. Consider non-invasive fibrosis assessment:

   • FIB-4 or NAFLD fibrosis score calculations
   • Elastography if available

3. Liver biopsy consideration:

   • If non-invasive tests suggest advanced fibrosis
   • If other etiologies cannot be excluded
   • To assess disease severity and guide management

Common Pitfalls to Avoid

• Don't assume normal ALT means mild disease: Normal ALT does not exclude significant liver pathology 3, 2
• Don't attribute AST elevation solely to NAFLD without investigation: Isolated AST elevation warrants evaluation of non-hepatic causes 1
• Don't rely solely on liver enzymes for disease monitoring: ALT has poor predictive value for NASH (AUROC 0.62) and advanced fibrosis (AUROC 0.46) 3
• Don't overlook cardiovascular risk: NAFLD patients have increased cardiovascular risk requiring assessment 1

Remember that the AST:ALT ratio typically reverses (becomes >1) in advanced NAFLD, so this pattern with elevated AST but normal ALT could indicate progression of liver disease and requires thorough evaluation.