A new diagnostic tool to improve clinical trials on MASH (NASH), or “fatty liver disease”.
In clinical drug trials, liver biopsy is now the standard examination required to diagnose metabolic steatohepatitis or MASH (formerly known as NASH). This condition, also known as “fatty liver disease”, is a liver disease that affects over 18% of the French population.
However, liver biopsy is invasive and often feared by patients, making it difficult to carry out therapeutic trials.
Prof. Vlad Ratziu, hepatologist and renowned teacher-researcher in the treatment of MASH, has taken part in a research project aimed at proposing alternative solutionsthrough the use of a blood test called NIS2+™.
Discover below the key findings of its scientific publication “NIS2+TM as a screening tool to optimize patient selection in metabolic dysfunction-associated steatohepatitis clinical trials”, published on December 5, 2023 in the Journal of Hepatology.
What is MASH or hepatic steatosis?
Today, 18.2%* of the French population are affected by hepatic steatosis (MASH – formerly NASH), a liver disease caused by an accumulation of fat of metabolic origin, independent of alcohol consumption or viral hepatitis*.(source: INSERM Constances cohort). This figure could rise to 24% by 2030.
This cardiometabolic disease is very often the consequence of an excessively sedentary lifestyle, combined with a diet too rich in fats and sugars. Le risque est une évolution vers des maladies graves telles que la cirrhose ou le cancer du foie.
People with MASH are often asymptomatic and at greater risk of developing cardiovascular disease, hypertension or diabetes.
The method: using the NIS2+™ test in diagnosis
A better selection of patients prior to liver biopsy would reduce the failure rate in clinical trials.
Standard fibrosis biomarkers (FIB)-4 do not detect progressive forms of metabolic steatohepatitis (MASH).
The work carried out by GENFIT, in collaboration with IHU ICAN, therefore compared the performance of screening incorporating the NIS2+™ test, based on a blood test, against current practices which involve biopsying patients simply on the basis of unspecific clinical information.
This NIS2+™ test was developed by the French biotechnology company GENFIT, based on a large collaborative international database. It allows to reduce the number of biopsies by better targeting patients likely to have the disease of interest, and to reduce the cost of carrying out these tests.
A retrospective simulation analysis was conducted in the diagnostic pathway of the RESOLVE-IT cohort, integrating the calculation and comparison of the following elements:
- Liver biopsy failure rate,
- Number of patients required for screening,
- Estimates of the overall cost of the various courses,
- Analysis of potential recruitment bias based on histology, gender, age or comorbidities.
The results: better use of liver biopsies
This study demonstrated that the use of the NIS2+™ test in selecting patients for liver biopsy significantly reduced unnecessary biopsies and screening costs, which could greatly improve the feasibility of clinical trials to combat MASH.
The cohort analyzed included 1,929 patients, 40% with at-risk MASH. The use of NIS2+™ significantly reduced the liver biopsy failure rate (39%) compared with non-specific biomarkers (58%) or the clinical diagnostic pathway alone (60%). This is accompanied by a significant reduction in associated costs.
The NIS2+™ test is an accurate and reliable screening tool that could improve patient recruitment in future MASH clinical trials, and increase comfort and safety for patients, while optimizing trial execution and cost-effectiveness.
IHU ICAN’s NASH (MASH) clinic
To improve diagnosis and earlier management of MASH (NASH), teams from AP-HP and IHU ICAN have set up the NASH clinic in 2019, headed by Pr Vlad Ratziu and Dr Raluca Pais.
This integrated care pathway aims to optimize diagnosis, provide patients with information (therapeutic education) and initiate a comprehensive care for people with hepatic steatosisThis includes diagnosis of all associated diseases (type 2 diabetes, hypertension, dyslipidemia, risk of heart attack or stroke).
The ultimate aim is to slow down, or even halt, the progression of MASH towards serious forms (cirrhosis, liver cancer), requiring major interventions such as liver transplantation.
