The aim of the present prospective NAFLD cohort study (with biobank), of obese subjects with proven NAFLD based on liver biopsy and/or MRI, is to study factors contributing to the development of NASH in patients with simple steatosis and to identify and validate non-invasive markers for the diagnosis of NASH.

Non-alcoholic fatty liver disease (NAFLD) is with 20-30% the most prevalent liver disorder in Western society. Most patients with NAFLD have no or few, mainly aspecific symptoms; and generally there is a silent progression of simple steatosis to NASH and in the end liver-related morbidity and mortality.

Further insight in factors contributing to the initiation of NASH in patients with simple steatosis and early diagnosis are essential for identifying future therapeutic options and to limit the risk of complicated NASH (i.e. fibrosis, and cirrhosis with portal hypertension) HCC, liver-related mortality and extrahepatic morbidity.

This cohort study, with both a cross-sectional and a longitudinal part, will include obese subjects (BMI ≥ 30 kg/m2, age 18-65) with proven NAFLD based on liver biopsy and/or MRI.

All participants will be asked to complete several questionnaires (i.e. demographics, clinical data, SF-36, GAD-7 and PHQ-9, FFQ, SQUASH, and Baecke), and to undergo anthropometric measurements. Furthermore, blood, urine, faeces and exhaled air will be collected and a fibroscan and DEXA-scan will be performed. Additionally, participants will be asked to participate in a multi-sugar test for intestinal permeability.

The majority of eligible subjects will undergo/have undergone a MRI or liver biopsy for clinical reasons. It is to be expected that about 33% of subjects will be asked to undergo a MRI for study purpose only.

After 5 and 10 years, participants will be invited to undergo in the same study procedures, data and sample collection to study the factors responsible for the development of NASH in the group with simple steatosis at baseline, and the development of (extra)hepatic complications in the group with NASH at baseline.

Inclusion Criteria:

• NAFLD diagnosis based on evidence of hepatic steatosis, either by imaging (using MRI) or by histology.
• BMI ≥ 30 kg/m2
• Between 18 - 65 years of age

Exclusion Criteria:

• Incompetent to understand and/or sign the informed consent.
• Causes for secondary hepatic fat accumulation such as significant alcohol consumption, medications, Wilson's disease, viral infections, starvation or parenteral nutrition, among others, and conditions associated with microvesicular steatosis
• Ethanol consumption exceeding more than 14 standard beverages per week for males and more than 7 standard beverages per week for female.
• Not able or willing to undergo MRI (for example claustrophobia, ICD, pacemaker).
• Not willing to be informed about unexpected findings by MRI
• Unwilling to collect bio samples.
• Pregnancy and breastfeeding.
• Indication or planned for bariatric surgery within one year after inclusion or a history of bariatric surgery.
• Diagnosis of liver cirrhosis and/or hepatocellular carcinoma.
• Current diagnosis of extrahepatic malignancy(s) or prior diagnosis within last 5 years.
• Individuals about to undergo or recovering from a surgical or otherwise medical procedure that will interfere with data collection and analyses planned within the current cohort, will initially be excluded from participation, but are offered the opportunity to participate at a later moment in time

Obese ( BMI ≥ 30 kg/m2) subjects with proven NAFLD either by imaging (using MRI) or histology, referred to secondary or tertiary care for obesity related problems will be asked to participate in this study.