Non-alcoholic steatohepatitis (NASH) typically progresses asymptomatically, often until patients develop irreversible cirrhosis. Consequently, early diagnosis is key – but remains challenging.
Even though NAFLD is common, routine screening is not recommended, even in high-risk individuals.
A number of factors may prompt assessment of a patient for NAFLD or NASH. The presence of obesity, diabetes, hypertension and hypercholesterolemia may raise the index of suspicion. Elevated liver enzymes, particularly alanine aminotransferase (ALT) and aspartate aminotransferase (AST), could prompt further evaluation, as could incidental findings of hepatic steatosis on imaging.
While the definitive diagnostic test for NASH is a liver biopsy, the cost and risks associated with it typically leads physicians and patients to explore less invasive methods to understand liver disease, once viral and genetic causes are ruled out.[i],[ii] While several companies offer blood tests for NASH, the U.S. Food and Drug Administration has yet to approve any.
No non-invasive biomarkers have been developed that reliably differentiate whether a patient has NASH or NAFLD. The Biomarkers Consortium’s Noninvasive Biomarkers of Metabolic Liver Disease (NIMBLE) project, however, has identified five biomarkers that could soon enable non-invasive assessment as they all outperform current liquid biopsies for NASH – Enhanced Liver Fibrosis (ELF), NIS4, PROC3, Fibrometer-Vibration-controlled elastography (VCTE) and OWLiver.[iii]
The issue is of such importance that the FDA has hosted multiple conferences 2023 to discuss the use and facilitate development of biomarkers for diagnosing and assessing treatment response in noncirrhotic NASH trials.[iv],[v]
Identification of fibrosis
Because patients with NASH with fibrosis stage 2 or higher are at the greatest risk of progression to cirrhosis and other negative outcomes, identifying these individuals is the highest priority.
To date, imaging has shown limited ability to distinguish between NAFLD and NASH, but transient elastography, a type of ultrasound, and magnetic resonance elastography, which combines elements of ultrasound and MRI to provide a visualization of stiffness throughout the liver, have proved to reliably identify liver fibrosis.[vi]
The Fibrosis-4 (Fib-4) score and AST-to-platelet ratio also indicate the degree of fibrosis.
