BEYOND ALT & AST Screening and Risk Assessment
Assessment Tools for MASLD/MASH A concise reference to commonly used tests for fibrosis risk in clinical practice
It starts with excess ectopic fat: Once the liver accumulates small amounts of liver fat, the liver is functionally impaired and insulin resistant. When more than 5% fat has accumulated, steatosis or “fatty liver” is present and, in the presence of at least one cardiometabolic risk factor like type 2 diabetes or abdominal obesity, the diagnosis of MASLD is official. 1,2,3,4 “The excess fat in hepatocytes puts stress on them,” says Wajahat Mehal, MD, PhD, DPhil, with Yale University in New Haven, CT. While triglycerides per se are not believed to damage hepatocytes, other lipid intermediates, such as ceramides or diacylglycerol, likely result in the death of liver cells; cell death results in more inflammation and scarring. 5 With enough fibrosis, the liver becomes cirrhotic. Hepatocellular carcinoma (HCC) can develop. 6 For most, it’s a slow, chronic disease, and it can take up to 20+ years to advance from stage F1 to F4. 6,7 But nearly 20% of people with MASH progress rapidly and can reach cirrhosis in just 5 years. 2,8 ALT has traditionally served as a marker for hepatocellular injury, but it does not directly reflect accumulated fibrosis.
ALT Marker
Damaged liver cells spill ALT into the blood. The ALT blood test reflects active hepatocellular injury. 9 Pro
Con
ALT alone doesn't measure fibrosis & isn't strongly correlated to disease severity. 8 “Normal” ALT can occur with severe fibrosis. ALT improvements don't always reflect structural liver changes. AST is less liver-specific than ALT & could reflect other conditions. AST can appear normal while disease worsens. AST/ALT ratio predicts cirrhosis severity. FIB-4 index incorporates AST/ALT ratio. Best for advanced disease where platelets are very low. Can give false positive/negative. Should not be used in patients under 35, and, though debated, the cutoff point to determine "low risk" for those 65 and older is 2.0, instead of 1.3. 1
AST
Damaged liver cells release AST into the blood, but so too can other organs like the kidney.
FIB-4
A simple formula that includes ALT, AST, age, and platelet count. The FIB-4 score should be less than 1.3, and it should be rechecked in 1–3 years. 2
ELF
A blood test to assess the progress of advanced liver fibrosis & identify those at risk of cirrhosis or liver-related outcomes. 6 Repeat in 1–3 years.
The optimal cut-off point for ELF is still being researched.
Abdominal ultrasound
Can reveal presence of liver fat (but can also miss it). 7
Cannot provide a quantitative measure of fat and does not assess inflammation or fibrosis. 8 VCTE may not be available in all clinical settings, but shear wave is available at most imaging centers. An ELF test can be used as a secondary risk assessment. 8
Vibration- controlled transient elastography (VCTE) and other methods Magnetic resonance elastography (MRE)
VCTE is an ultrasound method that measures liver stiffness to estimate fat percentage and severity of fibrosis. Shear wave elastography can also be used. 3
Imaging-based method that helps identify fibrosis stage. More accurate than VCTE in earlier stages.
Cost and accessibility may be prohibitive in some clinic settings.
Biopsy
Considered to be the gold standard to measure liver fat, fibrosis, and cirrhosis. Usually conducted when noninvasive tests are inconclusive. 8
Can produce a false negative: Fat and fibrosis are not equally distributed throughout liver, so one sample may show different results compared with another elsewhere in the liver. 1
SCAN FOR STEPS TO DIAGNOSIS
14 Healthful Living Rx
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