November 15, 2021
3 minutes to read
Source / Disclosures
Sanyal AJ. Main results of the NIMBLE stage 1-NASH CRN study of circulating biomarkers of non-alcoholic steatohepatitis and its activity and stage of fibrosis. Presented at: The Liver Meeting Digital Experience; 12-15 Nov 2021 (virtual meeting).
Sanyal is on an advisory or review committee for Axcella Health; board for 89Bio, Affyimmune, Albireo, Allergan, Amra, Ardelyx, Astra Zeneca, BASF, Bird Rock, Boehringer Ingelheim, Chemomab, Cirius, Conatus, ENYO, Echosens, Elsevier, Fractyl, Genentech, General Electric, GENFIT, Gilead, HemoShear, Immuron, IFMO, Innovate, Intercept, Inventiva, Janssen, Lilly, Lipocine, Mallinckrodt, NGM Bio, Nimbus, Nitto Denko, NorthSea Therapeutics, Novartis, Novo Nordisk, OWL, Perspectum, Pfizer, Poxel, Redx, Sagimet, Salix, Sanofi Servier , Second Genome, Sunrise, Takeda, Terns, Teva, UpToDate and Zydus; work for Sanyal Bio; receiving grant / research support from Allergan, Boehringer Ingelheim, Intercept, Inventiva, Bristol Myers, Cirius Therapeutics, Cumberland, Echosens, Galectin, Galmed, Gilead, Intercept, Karius, Madrigal, Mallinckrodt, Merck, Novartis, Pfizer, Salix, Second Genome, Sequana and Thera technologies; and holding stocks in Akarna, Durect, Exhalenz, Galmed, Genfit, Indalo, Sanyal Bio, Tiziana.
To streamline and validate diagnosis and clinical trials in non-alcoholic steatohepatitis, a group is tasked with determining the best non-invasive tests that all physicians can use, according to a presentation.
“As you know, there are many non-invasive tests in development, but there are very few that are actually approved for any setting of use. ” Arun J. Sanyal, MBBS, MARYLAND, professor in the department of internal medicine in the division of gastroenterology, hepatology and nutrition at the Virginia Commonwealth University School of Medicine, told The Liver Meeting Digital Experience. “In this cross-sectional analysis of several panels of biomarkers in the same blood sample from a highly phenotyped NAFLD population, several biomarkers met the a priori criteria of preliminary success. … There was different performance between biomarkers for NASH and for fibrosis, making it likely that future combinatorial approaches could be used to improve the diagnostic position.
In the NIMBLE collaboration with the NASH Clinical Research Network (CRN), researchers examined 1,073 screened patients with NAFLD (n = 220) or NASH (n = 853) divided according to the stages of fibrosis: F0 (n = 222; mean age, 47.8 years; 44.6% men; 71.2% white), F1 (n = 114; mean age, 48.1 years; 45.6% men; 59, 6% white), F2 (n = 262; mean age, 51.7 years; 38.9% men; 76.2% white), F3 (n = 277; mean age, 54.4 years; 32.9% male; 78.9% white) and F4 (n = 198; mean age, 56.2 years; 30.3% male; 86.2% white). They analyzed the results of the following tests performed within 90 days of a liver biopsy: NIS4 (Genfit), Enhanced Liver Fibrosis score (ELF, Siemens Healthineers), FibroMeter VCTE (FM-VCTE, Echosens), PRO-C3 (Nordic Biosciences) and unidirectional lipidomics (OWL, OWLiver). Each technique was compared to FIB4 and ALT.
“We really need to analyze it very finely to see if we’re going to use it for diagnosis, for prognosis, for monitoring disease, for predicting response to treatment. Each is somewhat considered a different context of use and each needs to be assessed independently, ”Sanyal said. “We felt that our immediate goal was to try to identify the population at risk of having more liver results.”
The NIS4 test met the diagnostic criteria for NASH and NAFLD Activity Score (NAS) of 4 or greater, while NIS4, ELF, and FM-VCTE all met the diagnostic criteria of F2 or greater. ELF and FM-VCTE improved for F3 and F4.
In researching a diagnosis of NASH, the group showed that NIS4 had an area under the curve (AUROC) of 0.832 versus 0.678 for ALT, positioning it to be precise (P <.001 likewise nis4 outperformed alt for nafld activity score with an auroc of versus>P <.001>
The OWL liver panel provides specific yes or no results, so Sanyal explained that there is no AUROC for this test, but he provided 63.3 for sensitivity and 75.4 for sensitivity. specificity.
Sanyal showed that the ELF test was performed at 0.828 AUROC (P P
PRO-C3 was found to be superior to the unit range but not to FIB4 and “with increasing fibrosis performance decreased,” Sanyal said.
The FibroMeter VTCE was performed in 393 patients, showing an AUROC of 0.841 to 0.897 as the fibrosis progressed, making it superior to the unit line and FIB4 (all P <.001 sanyal noted that this subset of patients were the only ones who underwent a fibroscan within preset time frame.>
“Finally, I would like to point out that FIB4 also had fairly robust diagnostic characteristics for these fibrosis-related parameters,” Sanyal said in his presentation.
This first step in the NIMBLE study laid the groundwork, Sanyal said, clarifying the sensitivity and specificity for that group of people who would benefit most from knowing their disease status.
“The basis for looking at all of this was really based on panels whose analytical robustness in the lab is already established and meets regulatory standards, so we think when you take all of this data in total, we’ve now made substantial progress towards satisfaction of the evidence burden for the qualification of biomarkers for the enrichment of the diagnostic context of use for people with NASH with significant fibrosis of stage 2 or higher, ”said Sanyal. “We are very excited about these results. “
At NIMBLE Stage 2, Sanyal said these biomarkers will be integrated into imaging workflows to address types of disease surveillance use and create truly predictive models.
“It’s time to include the liver as a critical end organ associated with type 2 diabetes. Diabetologists often focus on kidney, heart, eye disease, etc., but many of these patients, especially those who progress to fibrosis and cirrhosis, will die of their liver disease, ”he said. “As most of these patients suffer from type 2 diabetes, it is now up to us to raise awareness among the diabetic population more, but by giving them the tools to identify it in their routine practice. “
“NIMBLE is an advanced qualification plan. We want something proven that every doctor can use over the next 2 years, ”Sanyal said.