What it measures: activity, fibrosis
Who should take it: diagnosed NAFLD/NASH patients
Where to get it: clinical trials
NIS4 is a blood-based diagnostic test developed by GENFIT that looks at liver activity and fibrosis to identify at-risk NASH patients. At-risk NASH patients are a subset of the general NAFLD/NASH population who are at a higher risk of progression to cirrhosis and adverse clinical outcomes. Because of the population subset being targeted, this test is not intended to be a screening test. These individuals have scores of NAFLD Activity Scores (NAS) ≥4 and Fibrosis Scores (F) ≥2.
Using the 4 biomarkers detailed in the above diagram, NIS4 uses its algorithm to assign patients a score from 0 to 1. Like other algorithm-based tests, the use of NIS4 eliminates concerns about variability between the diagnoses done by human pathologists.
In clinical trials, patients with a NIS4 score <0.36 were classified as not having at-risk NASH, while patients with a NIS4 score >0.63 were classified as having at-risk NASH. Those with NIS4 scores 0.36-0.63 were indeterminate, requiring further testing. As a test to rule out at-risk NASH (NIS4 .0.36), NIS4 has a negative predictive value of 77.9%. This means that 77.9% of those identified as not having at-risk NASH truly do not have at-risk NASH, while the remaining 22.1% are false negatives requiring further validation. As a test to rule in at-risk NASH (NIS4 >0.63), NIS4 has a positive predictive value of 79.2%. This means that 79.2% of those identified as having at-risk NASH truly do have at-risk NASH, while the remaining 20.8% are false positives requiring further validation.
This test is not yet widely available to patients because the biomarkers are uncommon in the typical lab setting and it is not yet reimbursable by insurance. GENFIT is working with LabCorp to increase availability of biomarker collection in their labs and is hoping to begin introducing the test to the public early in 2021.
 Harrison, Stephen et al., A blood-based biomarker panel (NIS4) for non-invasive diagnosis of non-alcoholic steatohepatitis and liver fibrosis: a prospective derivation and global validation study, The Lancet Gastroenterology & Hepatology, November 2020, doi: 10.1016/S2468-1253(20)30252-1.