NIS2+™: an effective blood-based test for the detection of at-risk NASH in older adults?

At-risk non-alcoholic steatohepatitis (NASH) is defined as NASH with NAFLD activity scores (NAS) ≥4 and significant fibrosis (F ≥ 2) diagnosed via histological scoring of liver biopsy.
PUBLISHED IN: Hepatology Communications (September 2023)


In the United States alone, 4.4% of the general population and 18.3% of individuals with type 2 diabetes are estimated to have at-risk NASH. Affected patients are at an increased risk of liver-related and all-cause mortality. Importantly, older adults, particularly those on Medicare, possess an even greater risk for progression to cirrhosis, acute or chronic liver failure, liver transplantation, and hepatocellular carcinoma. Despite the evident importance of early NAFLD detection, recent research involving Medicare recipients indicates that older patients are likely to be diagnosed with cirrhosis before being diagnosed with NASH.

This study aimed to assess the diagnostic performance of two new blood tests, NIS4® and NIS2+™, 1) in both younger (<65) and older (≥65) patients, and 2) against that of existing non-invasive tools (FIB-4, ELF™, alanine aminotransferase (ALT), and NAFLD fibrosis scores (NFS)) currently used to detect at-risk NASH. Importantly, 50% of the study participants were ≥65 years of age and represented the United States’ Medicare population.

Key learnings:

In patients who were <65 versus those ≥65 years of age, NIS4® and NIS2+™ demonstrated similar assay performance for the identification of at-risk NASH. Compared to other blood tests designed for advanced liver fibrosis, both NIS4® and NIS2+™ exhibited significantly smaller indeterminate or moderate risk zones. Importantly, however, in patients ≥65, NIS2+™ exhibited a higher AUROC than NIS4®, FIB-4, NFS, ELF™, and ALT. Moreover, it displayed a more balanced sensitivity and specificity at the low, high, and Youden cut-off points. Ultimately, NIS2+™’s robust and stable performance across both age subpopulations supports its clinical use for the early detection of at-risk NASH in older adults, particularly those ≥65 years of age.

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S Duarte, BSc

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