Global Research Initiative for Patients Screening on MASH

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.

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.