Low AST and ALT: Causes and Clinical Significance
Direct Answer
Low aminotransferase levels are most commonly caused by chronic hemodialysis, advanced age, vitamin B6 deficiency (though less common than previously thought), and severe malnutrition, with hemodialysis patients showing mean AST levels of 9.2 IU/L and ALT levels of 7.4 IU/L compared to normal adults at 22.7 and 18.0 IU/L respectively. 1
Primary Causes of Low Aminotransferases
Chronic Hemodialysis
- Patients undergoing long-term hemodialysis consistently demonstrate very low serum AST and ALT levels, with mean values approximately 60% lower than normal adults 1
- In a study of 304 hemodialysis patients negative for hepatitis B and C, mean AST was 9.2 ± 2.4 IU/L and ALT was 7.4 ± 1.7 IU/L, compared to 22.7 ± 5.4 and 18.0 ± 4.0 IU/L in normal adults 1
- This reduction is NOT primarily due to vitamin B6 deficiency, as previously believed—mean serum vitamin B6 and pyridoxal-5'-phosphate levels in dialysis patients were not reduced compared to controls 1
Clinical Implications in Hemodialysis Patients
- The upper normal limits of AST and ALT in hemodialysis patients should be reduced considerably, and these levels must be interpreted with extreme caution when diagnosing liver disease 1
- Standard reference ranges significantly overestimate normal values in this population, potentially missing active liver disease including chronic hepatitis C, which is common among hemodialysis patients 1
Differential Diagnosis of Low Aminotransferases
Nutritional and Metabolic Causes
- Severe malnutrition or cachexia can result in decreased aminotransferase production
- Vitamin B6 deficiency, while historically considered a primary cause, is actually an uncommon contributor to low aminotransferases even in at-risk populations 1
Age-Related Changes
- Advanced age may be associated with lower baseline aminotransferase levels, though this is less well-characterized than elevations
Important Diagnostic Considerations
- ALT is more liver-specific than AST because AST is present in cardiac muscle, skeletal muscle, kidneys, brain, and red blood cells, making ALT the most specific marker for liver damage 2
- When both enzymes are low, this suggests a systemic process rather than isolated liver pathology 1
Clinical Management Approach
When to Investigate Low Aminotransferases
- In hemodialysis patients: Establish population-specific reference ranges and monitor trends rather than absolute values 1
- In patients with suspected liver disease: Do not rely on standard reference ranges if aminotransferases are unexpectedly low—consider the clinical context and use alternative markers of liver function 1
- In nutritional assessment: Consider comprehensive nutritional evaluation including albumin, prealbumin, and vitamin levels
Monitoring Strategy
- For hemodialysis patients with chronic hepatitis C, even modest elevations above their baseline low values may indicate active disease 1
- Serial measurements are more valuable than single values when aminotransferases are chronically low 1
Critical Pitfalls to Avoid
- Do not assume normal liver function based on "normal" aminotransferase levels in hemodialysis patients—their baseline is significantly lower than standard reference ranges 1
- Do not attribute low aminotransferases solely to vitamin B6 deficiency without confirming deficiency through direct measurement, as this is rarely the primary cause 1
- Do not overlook liver disease in populations with chronically low aminotransferases—adjust diagnostic thresholds appropriately 1