Published On: 3/30/2023

Validation of a Pragmatic Clinical Risk-Based Classification of NASH - New Supporting Real World Evidence from TARGET-NASH

DURHAM, N.C., March 30, 2023 /PRNewswire/ -- New research published today by real-world evidence leader Target RWE validates a practical risk-based classification of nonalcoholic fatty liver disease (NAFLD). "Validation of a Clinical Risk-Based Classification System in a Large Nonalcoholic Fatty Liver Disease Real-world Cohort," was published in the peer-reviewed publication Clinical Gastroenterology and Hepatology. The research addresses an unmet need for simple and easily available noninvasive methods that can be used in routine practice to identify those at risk of adverse outcomes from NAFLD.

More than 20% of the US population is affected by NAFLD, which represents a major and growing public health concern with significant health economic implications. While there are no approved curative therapies to date, there are multiple new therapies currently under review with the FDA. Identifying patient populations in the real world who will need these upcoming treatments will be critical when these novel treatments become available. Traditional diagnostic tools, such as liver biopsy or elastography, are limited by either safety or access. Simple and standard-of-care surrogates to assess increased risk for NAFLD progression are needed. The TARGET-NASH paper validates a noninvasive, simple, and practical risk score based on standard-of-care surrogate measures (FIB-4) to identify NALFD populations at high risk for disease progression.

To address this, researchers conducted a retrospective-prospective analysis of NAFLD patients enrolled in TARGET-NASH, a longitudinal non-interventional study. The analysis was performed to validate the prognostic utility of three risk categories: Fibrosis-4 (FIB-4) less than 1.3 and/or liver-stiffness measurement (LSM) measured by Fibroscan less than 8kp; FIB-4 greater than 1.31 to less than2.6 and/or LSM greater than 8 and up to 12.5kp; and FIB-4 greater than 2.6 and/or LSM greater than 12.5kp.

"This study provides robust evidence linking a noninvasive surrogate of fibrosis in the liver, FIB-4, to several adverse outcome including hepatic decompensation, hepatocellular cancer, major adverse cardiovascular events and even risk of death. The cutoffs presented in this analysis can be used in real-world settings to help identify patients at highest risk so that providers can make informed treatment choices," said Arun J. Sanyal, M.B.B.S., M.D., Director of Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Interim Chair of Division of Gastroenterology, Hepatology, and Nutrition, Z. Reno Vlahcevic Professor of Medicine, Physiology, and Molecular Pathology, Virginia Commonwealth University School of Medicine. Dr. Sanyal is co-chair of the TARGET-NASH steering committee and is lead author of the study.

The study population included 2,523 participants who were available for analysis; median duration of follow up was 3.7 years (IQR:2.8-4.9) with 9,527.5 patient-years of follow-up. The principal outcome of the study was all-cause mortality. Other outcomes included liver associated clinical events (LACE, also referred to as major adverse liver outcomes (MALO)), major adverse cardiac events (MACE), hepatocellular cancer (HCC), a rise in MELD score from <12 to ≥15, and incident decline in renal function. LACE included variceal hemorrhage, encephalopathy and overt ascites; MACE included acute myocardial infarction, new onset angina, revascularization or hospitalization for heart failure.

Sponsored by Target RWE, TARGET-NASH is a longitudinal, observational cohort of adult and pediatric participants with NAFLD and/or NASH receiving usual care from academic and community centers in the U.S. and Europe, enrolling more than 7,000 participants to date. Real-world data is collected from consented participants, who may also provide patient-reported outcome measures and biospecimens. Learn about TARGET-NASH publications here.