The Franciscus Obesity NASH Study (FONS)

The purpose of this study is to evaluate Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) changes in terms of steatosis and elasticity in patients with morbid obesity 1, 3 and 5 years after bariatric surgery.

In addition, genomics, microbiome and metabolomics analyses will be carried out.

Study Overview

• Status: Active, not recruiting
• Conditions: NAFLD; Obesity, Morbid; NASH - Nonalcoholic Steatohepatitis
• Intervention / Treatment: Diagnostic test: NASH screening; Diagnostic test: Cardiac dysfunction screening; Diagnostic test: Liver biopsy

Detailed Description

After being informed about the study and potential risks, 300 eligible patients will be included.

All participants will undergo lifestyle intervention before bariatric surgery. Extensive cardiometabolic analyses will be carried out. At 5 different moments (twice before and 3 times after bariatric surgery), liver steatosis and elasticity will be evaluate using Fibroscan. For those with an elevated liver fibrosis measurement (TE ≥7.2 kilopascal with M probe or ≥7.95 kilopascal with extra large probe), a laparoscopic liver biopsy will be performed during surgery. Patients will undergo gastric sleeve resection, Roux-n-Y gastric bypass or gastric minibypass.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

Study Locations

• Netherlands
  • South Holland
    • Rotterdam, South Holland, Netherlands, 3045PM
      • Franciscus Gasthuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Participants with morbid obesity enrolled for bariatric surgery at the Franciscus Gasthuis, Rotterdam, the Netherlands.

Description

Inclusion Criteria:

Participants must fulfil all of the inclusion criteria (unless otherwise specified) for enrolment in the study.

1. Participants must fulfil the criteria of the International Federation for the Surgery of Obesity (IFSO) at screening.
2. Participants must be able to understand the nature of the study and written informed consent must be obtained before any study specific interventions are performed.

The cardiac function of a subset group of 30 subjects aged 35 years and older with low transient elastography measurements (≤F1) and no known cardiac disease, hypertension or diabetes mellitus will be compared with a similar number of patients with high transient elastography measurements (≥F3) and no known cardiac disease, hypertension or diabetes mellitus. These patients will be consecutively included.

The investigators will perform a liver biopsy during endoscopic bariatric surgery in the patients with an elevated transient elastography measurement (≥F2; suggesting fibrosis and therefore the presence of NASH) in order to correlate the histological diagnosis to the clinical diagnosis based on elastography. In those patients in whom the diagnosis of NASH is confirmed by histology, more detailed follow up in a separate program at the department of gastroenterology is indicated according to the current guidelines.

Exclusion Criteria:

Patients who meet any of the following criteria at screening (unless otherwise specified) will be excluded from the study:

1. Participants younger than 18 years or older than 65 years

2. Participants with an established diagnosis of liver pathology like, but not limited to:

   1. Hepatitis B
   2. Hepatitis C
   3. Autoimmune hepatitis
   4. Wilson's disease
   5. Hemochromatosis
   6. Primary biliary cholangitis
   7. Primary sclerosing cholangitis
   8. Alcoholic liver disease
3. Histologically documented liver cirrhosis (fibrosis stage F4), at screening or in a historical biopsy.
4. Participants with active HIV infection and/or treatment.
5. Participants with diagnosed malignancies with or without active treatment.
6. Participants with 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 complete the study.
7. The participant does not understand Dutch.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

FONS group; Patients with morbid obesity enrolled for bariatric surgery in the Franciscus Gasthuis, Rotterdam, the Netherland

Diagnostic test: NASH screening; Evaluate liver steatosis and elasticity using transient elastography in the FONS group; Diagnostic test: Cardiac dysfunction screening; Evaluate cardiac dysfunction in 60 patients from the FONS group with transthoracic echocardiography; Diagnostic test: Liver biopsy; For participants from the FONS group with an elevated liver fibrosis measurement (≥F2) with TE, a laparoscopic liver biopsy will be performed during the bariatric procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in liver steatosis (in decibel/meter) 5 years after bariatric surgery	Transient elastography is a non invasive test evaluating liver steatosis	baseline (enrolment) and 5 years after bariatric surgery
Change from baseline in liver fibrosis (in kilopascal) 5 years after bariatric surgery	Transient elastography is a non invasive test evaluating liver fibrosis	baseline (enrolment) and 5 years after bariatric surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between NAFLD/NASH and vascular dysfunction	To determine if the presence of NAFLD/NASH before bariatric surgery is associated with (subclinical) vascular dysfunction using the carotid intima media thickness and pulse wave velocity	baseline
Association between change in NAFLD/NASH and change in cardiac dysfunction	To determine if change of liver fibrosis stage is associated to change in cardiac function 1 year after bariatric surgery	baseline and 1 year after bariatric surgery
Change from baseline in liver steatosis (in decibel/meter) after lifestyle intervention	Transient elastography is a non invasive test evaluating liver steatosis	baseline (enrolment) and 3 months later
Change from baseline in liver fibrosis (in kilopascal) after lifestyle intervention	Transient elastography is a non invasive test evaluating liver fibrosis	baseline (enrolment) and 3 months later
Change from baseline in liver steatosis (in decibel/meter) 1 year after bariatric surgery	Transient elastography is a non invasive test evaluating liver steatosis	baseline (enrolment) and 1 year after bariatric surgery
Change from baseline in liver fibrosis (in kilopascal) 1 year after bariatric surgery	Transient elastography is a non invasive test evaluating liver fibrosis	baseline (enrolment) and 1 year after bariatric surgery
Change from baseline in liver steatosis (in decibel/meter) 3 years after bariatric surgery	Transient elastography is a non invasive test evaluating liver steatosis	baseline (enrolment) and 3 years after bariatric surgery
Change from baseline in liver fibrosis (in kilopascal) 3 years after bariatric surgery	Transient elastography is a non invasive test evaluating liver fibrosis	baseline (enrolment) and 3 years after bariatric surgery
Change from baseline in liver steatosis (in decibel/meter) according to the type of bariatric surgery	To evaluate if the type of bariatric surgery (gastric sleeve resection, Roux-en-Y Gastric bypass, Gastric minibypass) influences the steatosis in patients with morbid obesity, measured 1 and 3 years after bariatric surgery, adjusted for baseline steatosis/elasticity.	baseline and 1 and 3 years after bariatric surgery
Change from baseline in liver fibrosis (in kilopascal) according to the type of bariatric surgery	To evaluate if the type of bariatric surgery (gastric sleeve resection, Roux-en-Y Gastric bypass, Gastric minibypass) influences the elasticity in patients with morbid obesity, measured 1 and 3 years after bariatric surgery, adjusted for baseline steatosis/elasticity.	baseline and 1 and 3 years after bariatric surgery
Change from baseline in liver steatosis (in decibel/meter) according to the genetic profile	To determine if candidate genetic markers (PNPLA3, TM6SF2, MBOAT7, GCKR and HSD17B13) are associated to changes in NAFLD/NASH severity in patients with morbid obesity one year after bariatric surgery.	baseline and 1 year after surgery
Change from baseline in liver fibrosis (in kilopascal) according to the genetic profile	To determine if candidate genetic markers (PNPLA3, TM6SF2, MBOAT7, GCKR and HSD17B13) are associated to changes in NAFLD/NASH severity in patients with morbid obesity one year after bariatric surgery.	baseline and 1 year after surgery
Change from baseline in liver steatosis (in decibel/meter) according to gender and ethnicities	To determine if liver steatosis differs between gender or ethnicities before bariatric surgery and the changes 1, 3 and 5 years after bariatric surgery	baseline and 1, 3 and 5 years after bariatric surgery
Change from baseline in liver fibrosis (in kilopascal) according to gender and ethnicities	To determine if liver elasticity differs between gender or ethnicities before bariatric surgery and the changes 1, 3 and 5 years after bariatric surgery	baseline and 1, 3 and 5 years after bariatric surgery
Change from baseline in liver steatosis liver steatosis (in decibel/meter) according to the gut microbiota	To investigate the change in the ratio of Firmicutes/Bacteroides in the distal gut microbiota in patients with morbid obesity with NAFLD/NASH 1 year after bariatric surgery and the effects of these changes on transient elastography measurements.	baseline and 1 year after bariatric surgery
Change from baseline in liver steatosis liver fibrosis (in kilopascal) according to the gut microbiota	To investigate the change in the ratio of Firmicutes/Bacteroides in the distal gut microbiota in patients with morbid obesity with NAFLD/NASH 1 year after bariatric surgery and the effects of these changes on transient elastography measurements.	baseline and 1 year after bariatric surgery
Association between NAFLD/NASH and cardiac dysfunction	To determine if the presence of NAFLD/NASH before bariatric surgery is associated with (subclinical) cardiac dysfunction using transthoracic echocardiography	baseline and 1 year after bariatric surgery
Correlation between histology and transient elastography measurement in a population with morbid obesity	To establish the correlation between histology (liver biopsy) and transient elastography measurement in a population with morbid obesity	during surgery

Collaborators and Investigators

• Sponsor: Franciscus Gasthuis
• Collaborators: Erasmus Medical Center; Leiden University Medical Center; Amsterdam UMC

Publications and helpful links

General Publications

• Theel WB, Boxma-de Klerk BM, Dirksmeier-Harinck F, van Rossum EF, Kanhai DA, Apers JA, van Dalen BM, De Knegt RJ, Neecke B, van der Zwan EM, Grobbee DE, Hankemeier T, Wiebolt J, Castro Cabezas M. Effect of bariatric surgery on NAFLD/NASH: a single-centre observational prospective cohort study. BMJ Open. 2023 Jul 3;13(7):e070431. doi: 10.1136/bmjopen-2022-070431.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Actual): September 1, 2023
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: August 11, 2022
• First Submitted That Met QC Criteria: August 11, 2022
• First Posted (Actual): August 12, 2022

Study Record Updates

• Last Update Posted (Estimated): August 27, 2025
• Last Update Submitted That Met QC Criteria: August 20, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Bariatric surgery; Transient elastography
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Digestive System Diseases; Liver Diseases; Overweight; Obesity; Fatty Liver; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Non-alcoholic Fatty Liver Disease; Obesity, Morbid
• Other Study ID Numbers: FONS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data are available upon reasonable request. The data that will be shared is individual participant data that underlie the results reported in the study, after deidentification (text, tables, figures and appendices). Also, the study protocol will be available. Data will be available beginning 9 months and ending 36 months following publication, for researchers who provide a methodologically sound proposal for any purpose. Proposals may be directed to w.theel@franciscus. nl up to 36 months following article publication. After 36 months, the data will be available in our hospital's data warehouse but without investigator support other than deposited metadata.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No