Research & Development

Scientific Background

Diagnosis of NAFLD/NASH

Initial diagnosis of NAFLD/NASH is based on elevated levels of liver enzymes (serum aminotransferase levels) in blood tests. When further evaluation excludes other reasons for liver disease, such as medications, viral hepatitis, or excessive use of alcohol, non-invasive imaging tests such as ultrasound, CT and MRI are acceptable indicators of the presence of NAFLD/NASH, but not reliable in assessing the degree of inflammation and fibrosis, which would help professionals distinguish between NAFLD and NASH. Moreover, some of these tests exhibit high rates of false negatives, with up to 20% of NAFLD patients showing normal liver enzyme levels, and another 20% with normal liver imaging in ultrasound and CT tests.

The “standard-of-care” used to diagnose NASH is a liver biopsy, which is the most reliable approach for identifying the degree of inflammation and fibrosis. However, the procedure-related mortality and morbidity, sample errors and costs limit its use to patients with a high index of suspicion of NASH (patients with metabolic syndrome and an indication of NAFLD by non-invasive diagnostic methods).

Since awareness to NAFLD/NASH is on the rise, several new non-invasive methods for diagnosis have been developed, or are under development. Among those, Nuclear Magnetic Resonance Spectroscopy (NMRS) is a validated, non-invasive technique for in-vivo fat and metabolite quantification. NMRS is routinely used for measuring triglycerides and potentially other liver fat components, and is increasingly being used as an endpoint in clinical trials and observational studies.

Lately, there has been a growing interest in the development of clinical prediction algorithms and biomarkers, such as NAFLD fibrosis score, Enhanced Liver Fibrosis (ELF) panel score and circulating biomarkers, such as CK-181.

More recently, several non-invasive diagnostic kits have been introduced to the market, some of which are eligible for insurance reimbursement in certain jurisdictions. Two of those are:

FibroMAXTM is a panel of patented biomarkers for estimation of levels of fibrosis (FibroTest®), NAFLD (SteatoTest®) and NASH (NashTest®). The panel combines markers of age and gender, total bilirubin, GGT, haptoglobin, apolipoprotein A1 and alpha2-macroglobulin, weight, height, total cholesterol, triglycerides, ALT, AST and fasting glucose.

FibroScanTM is a sonography-based non-invasive test for liver fibrosis assessment. The scanner is designed to quantify liver fibrosis by means of elastography; based on changes of the physical properties of the liver during chronic liver injury. This technique has been evaluated most consistently in patients with chronic HCV disease2

[1] Chalasani N, Younossi Z et al., “The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology“, Gastroenterology. 2012 Jun;142(7):1592-609

[2] Bensamoun SF, Wang L, Robert L, et al. Measurement of liver stiffness with two imaging techniques: magnetic resonance elastography and ultrasound elastography. J Magn Reson Imaging. 2008;28:1287-1292