MASH: A Silent Disease with a Growing Burden
MASH (Metabolic Dysfunction-Associated Steatohepatitis), formerly known as NASH, is a liver disease that is often asymptomatic and difficult to detect at an early stage. Associated with metabolic risk factors such as obesity, prediabetes, type 2 diabetes, hypertension and dyslipidemia, MASH can progress to severe complications including cirrhosis, liver decompensation events or Acute-on-Chronic Liver Failure (ACLF), liver cancer, including extrahepatic complications. Some patients are at increased risk of progression to more advanced stages of the disease, referred to as “at-risk” MASH.
In the U.S.1, studies suggest that by 2033 approximately 260 million adults could present risk factors for metabolic diseases, around 170 million could be diagnosed with metabolic diseases, and nearly 90 million could exhibit elevated liver enzymes and/or steatosis.
A Therapeutic Turning Point Reinforcing the Importance of Diagnosis
2024 marked a turning point in the management of MASH with the FDA approval of the first treatment specifically indicated for this disease, followed by its commercial launch in the U.S. market in 2025.
For years, liver biopsy was considered the reference method in clinical trials. However, its invasive nature and associated constraints, including cost and procedure-related risks, have significantly limited its use on a large scale. In real-world clinical practice, blood-based tests and non-invasive imaging methods available until recently still lacked the accuracy needed to reliably identify patients.
In this new therapeutic landscape, the early identification of patients with “at-risk” MASH through reliable, accessible, and non-invasive diagnostic tools is a major unmet medical need.
NASHnext®, NIS4® and NIS2+®: Solutions Designed to Address the Challenge of Non-Invasive Diagnosis
A pioneer in MASH, GENFIT has been developing non-invasive diagnostic tools since 2015 to help identify patients at risk of progressing to more severe stages of the disease. These technologies are supported by a unique clinical and biological dataset, including liver biopsies and blood samples collected from thousands of patients enrolled in GENFIT-sponsored clinical trials.
GENFIT’s proprietary NIS4® and NIS2+® technologies are based on the identification and measurement of specific blood biomarkers associated with MASH, disease severity, and liver fibrosis stage.
Based on licensed NIS4® technology, NASHnext® is a non-invasive laboratory-developed test (LDT) marketed by Labcorp in the U.S. and designed to identify patients with “at-risk” MASH. Recent coverage and reimbursement milestones are expected to support broader adoption in clinical practice.
In parallel, GENFIT is advancing the development of an in vitro diagnostic (IVD) test kit based on its proprietary NIS2+® technology, and is actively exploring opportunities with potential commercial partners, with the ambition of making this diagnostic approach broadly accessible.s suggest that by 2033 approximately 260 million adults could present risk factors for metabolic diseases, around 170 million could be diagnosed with metabolic diseases, and nearly 90 million could exhibit elevated liver enzymes and/or steatosis.
Growing Scientific Recognition and Adoption for Diagnosis and Monitoring
NIS4® and its next-generation version, NIS2+®, are gaining increasing recognition within the scientific and medical communities due to their performance in identifying patients with “at-risk” MASH. This recognition is supported by a robust body of scientific evidence and publications in leading peer-reviewed journals, including The Lancet, Nature Medicine, and the Journal of Hepatology, across a range of use cases from diagnosis and patient monitoring to screening for clinical trials.
NIS technologies are also recognized through their inclusion in joint international society guidelines (EASL-EASD-EASO), their evaluation within major academic consortia in Europe and the United States, including NIMBLE and LITMUS, and their use in numerous clinical development programs conducted by leading pharmaceutical companies active in MASH.
Scientific Literature and Publications
Publications
- 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
- Diagnostic performance of circulating biomarkers for non-alcoholic steatohepatitis – Nature Medicine
- NIS2+™, an optimisation of the blood-based biomarker NIS4® technology for the detection of at-risk NASH: A prospective derivation and validation study – Journal of Hepatology
- NIS2+TM as a screening tool to optimize patient selection in metabolic dysfunction-associated steatohepatitis clinical trials – Journal of Hepatology
- Serial measurements of NIS2+® enable monitoring disease evolution in patients with MASH: A retrospective cohort analysis : Hepatology Communications
- High Prevalence of Metabolic Dysfunction–Associated Steatohepatitis With Significant Fibrosis in Primary Care and Endocrinology Clinics – Kalavalapalli – 2026 – Diabetes, Obesity and Metabolism
Guidelines
Evaluations
- Prospective validation of imaging and serum diagnostic biomarkers of steatohepatitis and fibrosis in MASLD: the LITMUS Imaging Study – Nature Medicine
- Diagnostic performance of circulating biomarkers for non-alcoholic steatohepatitis – NIMBLE – Nature Medicine
Posters
Sequential use of FIB-4 and NIS2+™ for an accurate detection of non-cirrhotic at-risk MASH patients for enrollment in mash clinical trials
Derivation and validation of the NIS2+™ blood-based biomarker panel, an improvement of NIS4® technology for the identification of at-risk NASH
NIS2+™ technology as a screening tool for enrollment of patients with at-risk NASH in clinical trials
NIS2+®, an effective tool for monitoring mash resolution and fibrosis improvement in patients with at-risk MASH
1Source: IQVIA