What is the Nash lab test for a patient with risk factors for liver disease, such as obesity or diabetes, particularly in the context of non-alcoholic fatty liver disease (NAFLD)?

What is the NASH Lab Test?

There is no single "NASH lab test" that can definitively diagnose nonalcoholic steatohepatitis (NASH)—liver biopsy remains the gold standard for diagnosis, though several blood-based biomarker panels and scoring systems can help predict the presence of NASH and advanced fibrosis in patients with suspected NAFLD. 1

Understanding NASH vs. NAFLD

• NASH is defined histologically as the presence of ≥5% hepatic steatosis with inflammation and hepatocyte injury (ballooning), with or without fibrosis 1, 2
• NASH represents the progressive form of NAFLD that can lead to cirrhosis, liver failure, and hepatocellular carcinoma, unlike simple steatosis (NAFL) which has minimal progression risk 3, 4
• Liver biopsy is the only method that can definitively distinguish NASH from simple fatty liver (NAFL) and assess the degree of fibrosis 5, 6

Blood-Based Biomarker Panels

NashTest

• The NashTest is a proprietary biomarker panel combining 13 parameters: age, sex, height, weight, triglycerides, cholesterol, alpha-2-macroglobulin, apolipoprotein A1, haptoglobin, gamma-glutamyl-transpeptidase (GGT), ALT, AST, and total bilirubin 7
• This test demonstrated an AUROC of 0.79 for diagnosing NASH with 94% specificity (positive predictive value 66%) and 33% sensitivity (negative predictive value 81%) 7
• The NashTest is not routinely available in standard clinical practice and requires specialized laboratory testing 5

Cytokeratin-18 Fragments

• Cytokeratin-18 fragment levels showed promise as a screening test for NASH with sensitivity of 78%, specificity of 87%, and AUROC of 0.82 in meta-analysis 5
• This marker is currently unavailable in routine clinical practice, and standard cut-off values have not been established 5

Recommended Clinical Approach for Risk Stratification

Initial Screening: Fibrosis-4 Index (FIB-4)

• The FIB-4 is the most cost-effective first-line test for screening patients with type 2 diabetes, prediabetes, obesity, or cardiometabolic risk factors 2
• FIB-4 is calculated from age, ALT, AST, and platelet count (available at mdcalc.com/calc/2200/fibrosis-4-fib-4-index-liver-fibrosis) 2
• This test identifies patients at risk for clinically significant fibrosis (F2-F4), not NASH specifically, but advanced fibrosis is the key prognostic factor 2
• FIB-4 should be used even in patients with normal liver enzymes, as 50% of NAFLD patients and many with significant fibrosis have normal transaminases 8, 1

Secondary Risk Stratification

• Patients with indeterminate or high FIB-4 scores should undergo liver stiffness measurement with transient elastography (vibration controlled transient elastography, VCTE) or enhanced liver fibrosis (ELF) blood test 2, 1
• The NAFLD Fibrosis Score (NFS) is an alternative clinical decision aid that can identify patients at low or high risk for advanced fibrosis 1

Tertiary Evaluation

• Patients with indeterminate results or high risk for significant fibrosis should be referred to gastroenterology/hepatology for further workup, which may include liver biopsy 2

Standard Laboratory Findings in NASH

• Most patients present with mildly elevated AST and/or ALT with AST:ALT ratio <1 (though this may reverse in advanced disease) 8
• Normal or near-normal ALT does not exclude NASH—up to 50% of NAFLD patients have normal liver enzymes 8, 1
• Alkaline phosphatase and GGT may be mildly elevated, but bilirubin typically remains normal unless cirrhosis is present 8
• Elevated INR, hypoalbuminemia, or thrombocytopenia suggest cirrhosis or portal hypertension 8

Critical Pitfalls to Avoid

• Do not rely on elevated transaminases alone for screening—a cutoff of ALT >40 units/L would miss most individuals with NASH and significant fibrosis 2
• The American College of Gastroenterology considers upper limit of normal ALT to be 29-33 units/L for men and 19-25 units/L for women 2
• Low titers of autoantibodies (ANA, anti-smooth muscle) are common in NAFLD and generally represent an epiphenomenon requiring no specific action unless titers are high (>1:160 for ANA or >1:40 for anti-smooth muscle) with other features of autoimmune disease 1
• Routine screening of all high-risk patients is not currently recommended due to uncertainties about treatment options and cost-effectiveness, though maintaining high clinical suspicion in patients with type 2 diabetes is essential 1

Histologic Scoring Systems

When liver biopsy is performed, several validated scoring systems exist:

• NAFLD Activity Score (NAS): An unweighted composite of steatosis, lobular inflammation, and ballooning scores used primarily in clinical trials 3, 1
• SAF score: A semiquantitative system consisting of steatosis amount, activity (lobular inflammation plus ballooning), and fibrosis 1
• Brunt system and NASH CRN system: Alternative grading and staging methods with specific merits for different clinical contexts 9