What are the options for a non-invasive liver (liver) screening test?

From the Guidelines

A non-invasive liver screen should start with the FIB-4 score, a simple and non-proprietary fibrosis score, to assess for clinically significant liver fibrosis, as recommended by the most recent and highest quality study 1. The FIB-4 score has been shown to have the best diagnostic accuracy for advanced fibrosis compared to other non-invasive markers of fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) 1.

• The FIB-4 score is calculated using a combination of age, platelet count, and liver enzymes (AST and ALT) 1.
• A FIB-4 score <1.3 (<2.0 in those older than 65 years) can reliably exclude advanced fibrosis in patients with NAFLD, with a negative predictive value of ≥90% 1.
• Patients with a FIB-4 score >2.67 are at high risk for advanced fibrosis and should be referred to hepatology for further evaluation, including liver stiffness measurement (LSM) or liver biopsy 1.
• For patients with an indeterminate FIB-4 score (1.3-2.67), additional testing, such as LSM, may be necessary to determine the stage of liver fibrosis 1.
• The use of non-invasive fibrosis tests, such as FIB-4, is supported by recent guidelines, including the EASL clinical practice guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 2021 update 1, and the EASL-EASD-EASO clinical practice guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD): executive summary 1.
• These guidelines recommend a multi-step approach, starting with a non-patented blood-based score, such as FIB-4, followed by imaging techniques, such as liver elastography, to further clarify the fibrosis stage if fibrosis is still suspected or in high-risk groups 1.

From the Research

Non-Invasive Liver Screen

• The most common causes of mildly elevated transaminase levels are nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease 2, 3.
• Uncommon causes of elevated transaminase levels include drug-induced liver injury, hepatitis B and C, and hereditary hemochromatosis 2, 3.
• Rare causes of elevated transaminase levels include alpha1-antitrypsin deficiency, autoimmune hepatitis, and Wilson disease 2, 3.
• Extrahepatic sources, such as thyroid disorders, celiac sprue, hemolysis, and muscle disorders, are also associated with mildly elevated transaminase levels 2, 4.

Diagnostic Approaches

• The initial evaluation of mildly elevated transaminase levels should include an assessment for metabolic syndrome and insulin resistance, a complete blood count with platelets, measurement of serum albumin, iron, total iron-binding capacity, and ferritin, and hepatitis C antibody and hepatitis B surface antigen testing 2, 3.
• The nonalcoholic fatty liver disease fibrosis score and the alcoholic liver disease/NAFLD index can be helpful in the evaluation of mildly elevated transaminase levels 2.
• The combination of a blood test and Fibroscan improves the non-invasive diagnosis of liver fibrosis 5.
• FIB-4, APRI, and AST/ALT ratio can be used to assess liver fibrosis in patients with NAFLD, with APRI being the most appropriate substitute for FibroScan 6.

Screening Tools

• Fibroscan is a useful tool for assessing liver fibrosis, but it may not be available in all settings 5, 6.
• Blood tests, such as FIB-4, APRI, and AST/ALT ratio, can be used to assess liver fibrosis in patients with NAFLD 6.
• The FIB-4 Index Score or NAFLD Fibrosis Score can be used to predict which patients are at risk for fibrosis and may benefit from further testing or referral to a hepatologist 3.