LFT Pattern in MASLD
In MASLD, liver enzymes are typically mildly elevated with ALT often exceeding AST (AST/ALT ratio <1), though this pattern is non-specific and many patients have completely normal transaminases despite significant liver disease.
Typical Biochemical Pattern
Aminotransferase Elevation
- ALT is usually higher than AST in early MASLD, reflecting hepatocellular injury from steatosis and inflammation 1
- The AST/ALT ratio typically remains <1 in non-cirrhotic MASLD, distinguishing it from alcohol-related liver disease where AST predominates 1
- As fibrosis progresses to cirrhosis, the AST/ALT ratio reverses and often exceeds 1.0, with an AST/ALT ratio ≥1.0 serving as a rule-in cutoff for advanced fibrosis (F3) 1
- Transaminase levels are often only mildly elevated (1-2 times upper limit of normal) or may be completely normal despite significant steatosis or even fibrosis 1
Critical Clinical Caveat
- Normal ALT does not exclude MASLD or advanced fibrosis – up to 30-40% of patients with biopsy-proven MASH have normal aminotransferases 2, 3
- Relying solely on elevated liver enzymes for case-finding will miss a substantial proportion of at-risk patients 1
Other Laboratory Findings
Alkaline Phosphatase and GGT
- Alkaline phosphatase may be mildly elevated but is typically less prominent than aminotransferases 2
- GGT elevation is common and correlates with metabolic dysfunction severity 4
Synthetic Function
- Albumin, bilirubin, and INR remain normal until advanced cirrhosis develops 2
- Platelet count progressively decreases with advancing fibrosis, serving as a component of fibrosis risk scores 1
Recommended Diagnostic Approach
Initial Assessment
- Do not rely on LFTs alone for diagnosis or risk stratification – the 2024 EASL-EASD-EASO guidelines emphasize case-finding in high-risk populations (type 2 diabetes, obesity, metabolic syndrome) regardless of transaminase levels 1
- Use FIB-4 score as the first-line non-invasive test for fibrosis risk stratification, incorporating age, AST, ALT, and platelet count 1, 5
- FIB-4 <0.66-0.89 rules out moderate fibrosis (F2)
- FIB-4 >2.67 rules in moderate fibrosis (F2)
- FIB-4 thresholds for advanced fibrosis (F3): <1.455 rules out, >0.676 rules in 1
Sequential Testing Algorithm
- Follow abnormal FIB-4 with vibration-controlled transient elastography (VCTE) to confirm fibrosis stage 1, 5
- Liver stiffness <8 kPa rules out advanced fibrosis (F3)
- Liver stiffness >12 kPa rules in advanced fibrosis (F3) 1
- MRI-based elastography (MRE) provides the highest accuracy for fibrosis staging when available, with cutoffs of 3.14 kPa for F2, 3.53 kPa for F3, and 4.45 kPa for F4 1
Metabolic Comorbidity Assessment
Mandatory Laboratory Evaluation
- At initial diagnosis and regular follow-up, assess for associated metabolic conditions including fasting glucose or HbA1c, lipid panel (triglycerides, HDL-cholesterol), and renal function 1
- Consider HOMA-IR or oral glucose tolerance test in patients without established type 2 diabetes to clarify insulin resistance 1
- Cardiovascular risk assessment is essential as cardiovascular disease is the leading cause of death in MASLD, exceeding liver-related mortality 2, 4
Common Pitfalls to Avoid
- Never dismiss MASLD based on normal transaminases – significant disease including advanced fibrosis can exist with completely normal ALT 1, 2
- Do not use AST/ALT ratio <1 to definitively exclude cirrhosis – while typical of early disease, individual variation exists and non-invasive fibrosis assessment is required 1
- Avoid using aminotransferase levels to monitor treatment response – changes in ALT correlate poorly with histological improvement at the individual patient level, though population-level associations exist 1
- Do not screen the general population – case-finding should target high-risk groups with cardiometabolic risk factors, abnormal liver enzymes, or imaging evidence of steatosis 1