Arterial Hypertension, Fibrosis, Liver, MASH, MASH With Fibrosis, MASLD, Metabolic Syndrome, Obesity, Steatosis of Liver, Type 2 Diabetes
Conditions
Keywords
MASLD, MASH, Screening, Patient care pathway
Brief summary
GRIPonMASH will assist (primary) health care providers clinicians to implement the latest patient care pathway, as described by the European Association for the Study of the Liver (EASL), to identify patients at risk of severe metabolic dysfunction-associated steatotic liver disease (MASLD) and to raise awareness. The primary objective is to implement a transmural patient care pathway, in order to identify patients with MASLD and its progressive form metabolic dysfunction-associated steatohepatitis (MASH) in primary care centres and clinics in 10 European countries.
Detailed description
GRIPonMASH is an observational study in which 10.000 high risk patients (type 2 diabetes mellitus, metabolic syndrome, obesity or arterial hypertension) in 10 different European countries will be screened for the presence of MASLD, liver fibrosis and (at-rsik) MASH using at least two non-invasive tests (FIB-4 and FibroScan). Additional published and exploratory non-invasive test will also be investigated. Blood samples and liver biopsy material will be collected. Genomic, proteomic, metabolomic, lipidomic and fluxomic studies will be applied to gain a better understanding of the pathophysiology of MASLD and to identify (bio)markers that will help to detect patients at-risk. The predictive value of FIB-4 in relation to FibroScan results and liver biopsy will be analysed. Long-term follow-up of 5 years in all participants will provide insight into the natural history of the disease.
Interventions
None listed
Sponsors
UMC Utrecht
Echosens
MIMETAS BV
Nordic Bioscience A/S
Elevate BV
Leiden University
Amsterdam University Medical Center
Andaluz Health Service
National Research Council, Institute of Clinical Physiology, Italy
Leiden University Medical Center
Université Libre de Bruxelles
University Hospital, Antwerp
Catholic University of the Sacred Heart
Medical Education Research And Innovation Center S.R.L.
EUROPEAN LIVER PATIENTS ASSOCIATION
Harokopio University
General University Hospital, Prague
Novo Nordisk A/S
Maastricht University
Mercodia Aktiebolag
EXIT071 BV
European Atherosclerosis Society
MetaDeq Limited
Associação para Investigação e Desenvolvimento da Faculdade de Medicina
Institute of Cardiometabolism and Nutrition, France
University Hospital, Saarland
Roche Pharma AG
Inventiva Pharma
Biocellvia
Franciscus Gasthuis & Vlietland (Hospital)
Julius Clinical
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed subjects should fulfil criteria for diagnosis of type 2 diabetes mellitus or metabolic syndrome or obesity or arterial hypertension, following the study definitions. * Subjects that are currently being treated for type 2 diabetes mellitus or metabolic syndrome or obesity or arterial hypertension, should have had a prior diagnosis based on study definitions. Study definitions: Type 2 diabetes mellitus * At least 2 times a fasting glucose \> 7,0 mmol/L * Or elevated non-fasting glucose \>11,1 mmol/L 2 hrs after OGTT * Or HbA1c ≥48 mmol/mol (≥6.5%) * Or being actively treated for previously diagnosed type 2 diabetes by a health care provider Obesity * Body mass index (BMI) \> 30 * Or waist circumferences Caucasian: male ≥ 94 cm, female ≥ 80 cm South-Asian/Chinese: male ≥90 cm, female ≥80 cm Japanese: male ≥85 cm, female ≥90 cm Arterial hypertension * Systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg * Or being actively treated for previously diagnosed arterial hypertension by a health care provider Metabolic syndrome \- Central obesity defined as waist circumference (see above), if BMI is \>30 kg/m2, central obesity can be assumed and waist circumference does not need to be measured AND any two of the following: * Raised triglycerides: ≥ 150 mg/dL (1.7 mmol/L), or specific treatment for this lipid abnormality * Reduced HDL cholesterol: \< 40 mg/dL (1.03 mmol/L) in males, \< 50 mg/dL (1.29 mmol/L) in females, or specific treatment for this lipid abnormality * Raised blood pressure (BP): systolic BP ≥ 130 or diastolic BP ≥ 85 mm Hg, or treatment of previously diagnosed hypertension * Raised fasting plasma glucose (FPG): FGP ≥ 100 mg/dL (5.6 mmol/L), or previously diagnosed type 2 diabetes (if above \>5.6 mmol/L or 100 mg/dL, an oral glucose tolerance test is strongly recommended, but is not necessary to define presence of the syndrome)
Exclusion criteria
* The patient is known with hepatitis B, C or HIV or any other liver condition (like hemochromatosis, sarcoidosis, Wilson's disease etc); * The patient is known with any other condition that may lead to liver fibrosis or cirrhosis; * The patient engages in (excessive) alcohol use: \> 3 units/day in males \[30 grams/day\] and \> 2 units/day in females \[20 grams/day\]; * The patient has a history or evidence of any other clinically significant condition or planned or expected procedure that in the opinion of the Investigator, may compromise the patient's safety or ability to be included in this study; * The patient is an employee or contractor of the facility that is conducting the study or is a family member of the Investigator, sub-Investigator, or any Sponsor personnel; * The patient is not able to understand the details of the protocol and/or is not able to provide written informed consent; * The patient is pregnant or breastfeeding. * The patient underwent bariatric surgery in the last 12 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of liver steatosis and MASLD estimated by FibroScan CAP in patients at risk | Baseline | Steatosis grade deduced from controlled attenuation parameter (CAP) measurement with Fibroscan |
| Prevalence of liver fibrosis estimated by FibroScan LSM in patients at risk | Baseline | Fibrosis stage deduced from liver stiffness measurement (LSM) by vibration controlled transient elastography (VCTE) measurement with Fibroscan |
| Prevalence of at-risk MASH estimated by FAST score in patients at risk | Baseline | At-risk MASH deduced from FAST score |
| *Subset of patients: prevalence of MASH in patients at risk | 16 or 30 weeks | MASH diagnosis confirmed by histology (NAS/SAF criteria) upon liver biopsy; only in patients with \>12 kPa at 1st FibroScan or \>=8 kPa at 2nd FibroScan |
| Comparison of the prevalence of MASLD, liver fibrosis and (at-risk) MASH between the participating countries | Baseline (1-3) to 16/30 weeks for biopsy-confirmed MASH (4) | Prevalence (see outcome 1-4) stratified per country |
| Evaluate added value of a 2-step pathway as compared to FibroScan only for detection of high-risk patients | Baseline | Number of patients at risk identified by FIB-4 compared to numbers found using LSM by VCTE with FibroScan measurements, and numbers found in combination |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| *Subset of patients: Second FibroScan examination | 14 weeks | CAP and LSM by VCTE at 2nd FibroScan examination |
| Build diagnostic model to identify MASH patients in a high-risk population | Baseline | Possible model parameters are all baseline clinical characteristics reported in the eCRF |
| Longitudinal changes in liver assessments | Baseline, 14 weeks + throughout follow-up (at 3 and 5 years) | Repeated CAP, LSM by VCTE and FAST measurements over time |
| Genotypes related to MASH in different European countries: Exploratory | Baseline | Genomic (GWAS) and proteomic analysis on collected blood samples |
| (Non-invasive) metabolite biomarkers identifying MASH in patients at risk: Exploratory | Baseline | Mass-spectrometry (MS) based metabolomic and lipidomic analyses on collected blood and samples, both targeted and untargeted approaches. |
| Prevalence of co-morbidities and associated therapies (especially for CVD) in patients with MASH compared to those without, in high-risk patient populations | Baseline | Prevalence of comorbidities, medication use, medical history |
| Identify prognostic factors/biomarkers for complications in patients with MASLD and MASH by 5 years follow up | Throughout follow-up (at 3 and 5 years) | Disease progression and liver-related and non-liver related complications |
| Patient Reported Outcomes: Dietary habits and lifestyle | Baseline + throughout follow-up (at 3 and 5 years) | 14 item Mediterranean Diet Score; lifestyle surveys |
Countries
Belgium, Czechia, France, Germany, Greece, Italy, Netherlands, Portugal, Romania, Spain
Contacts
Primary Contactde Jong
Backup ContactWijkhuis
Outcome results
None listed