Non-Invasive MASLD Diagnosis & T2D Remission Biomarkers

Active, not recruiting

• Conditions: MASLD; T2DM (Type 2 Diabetes Mellitus); Non-alcoholic Fatty Liver Disease (NAFLD); Obesity

• Registration Number: NCT07172997
• Lead Sponsor: Royal College of Surgeons in Ireland - Medical University of Bahrain

Brief Summary

The goal of this observational study is to prospectively develop and validate a non-invasive scoring system based on metabolic markers, proteomic, and transcriptomic profiles to accurately screen, diagnose, stage, and monitor Metabolic dysfunction-associated steatotic liver disease (MASLD) activity and regression as a replacement for the invasive liver biopsy tool in Bahraini bariatric patients. The study also aims to identify biomarkers for predicting type 2 diabetes mellitus remission post-bariatric surgery. The main questions it aims to answer are:

* What proteomic and transcriptomic markers can be used to accurately screen, diagnose, stage, and monitor MASLD activity and regression?

* What transcriptomic markers can predict type 2 diabetes mellitus remission? Researchers will compare the proteomic and transcriptomic profiles of bariatric patients before and after surgery to identify molecular changes associated with weight loss and normalization of metabolic biomarkers. The data will be used to design and validate a scoring system for MASLD diagnosis and monitoring.

Participants will undergo comprehensive assessments, including anthropometric measurements, metabolic biomarker evaluations, proteomic, and transcriptomic profiling at three time points: before surgery, and at 6- and 12-months post-surgery. The data collected will inform the development of the non-invasive scoring system, which will be tested for its reliability and accuracy in replacing liver biopsy as the standard diagnostic tool for MASLD.

Detailed Description

Metabolic dysfunction Associated Steatotic Liver Disease (MASLD), previously known as NonAlcoholic Fatty Liver Disease (NAFLD), is becoming the most common cause of liver disease in adults with the pandemic of obesity in this century. MASLD is affecting more than quarter of the whole population on earth and the highest prevalence is in the middle east region. A recent retrospective study performed on bariatric patients at the King Hamad University Hospital (KHUH) reported a prevalence of 82.3% of MASLD before the surgery. MASLD progression may lead to liver cirrhosis following which the liver cells become damaged irreversibly. The current gold standard to diagnose MASLD is liver biopsy, however, this method has several limitations due to its invasive nature.

This observational study aims to study MASLD in depth utilizing molecular analysis tools, which can yield more information about disease progression in bariatric patients specific to the Bahraini population.

The total sample size of our study is estimated to be around 163 participants of which 134 subjects would to be positive cases of MASLD. We will include the patients undergoing bariatric surgery from the January to December 2025. An informed consent will be taken from the patients to participate in the research while consenting them for the surgery. The surgeon will inform the participant that radiological and biochemical investigations will be done pre-operatively as well as wedge liver biopsy will be taken during the laparoscopic procedure.

Several data will be collected from the enrolled patients' medical records to study disease progression before the surgery, 6 months and 12 months after the surgery:

1. Anthropometric Measures including weight, hight, body mass index, etc.

2. Body composition data including fat mass, muscle mass, etc.

3. Routine bariatric profile blood results including liver enzymes, platelets, etc.

4. Abdominal ultrasonography reports.

5. Shear wave elastography radiological assessment

6. Proteomic and transcriptomic profiling outside Bahrain

Study Timeline

• Status Verified: 2025-01
• Study Start: 2025-01-01
• Study First Submitted: 2025-01-30
• Study First Submitted QC: 2025-09-08
• Last Update Submitted: 2025-09-08
• Study First Posted: 2025-09-15
• Last Update Posted: 2025-09-15
• Primary Completion: 2026-12-31
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 163

Inclusion Criteria

• Adult obese patients undergoing bariatric surgery in KHUH surgery department consented to be included in the study.

Exclusion Criteria

• Patients fail to complete the surgery due to intra-operative complications.
• Patients fail to retrieve liver biopsy sample from due to intra-operative difficulties.
• Patients with missing data pre-operatively
• Body Mass Index less than 30 kg/m2.
• Post-liver transplant patients
• Patients known to have any liver disease other than MASLD
• Patients with history of Alcohol Drinking.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Accuracy of Non-invasive Ultrasonography Tools for MASLD Assessment	At Baseline, at 6-months after the surgery, and at 12 months after the surgery	To assess the diagnostic accuracy of three ultrasonography tools for diagnosing MASLD by calculating their sensitivity (%), specificity(%), positive predictive value (PPV)(%), and negative predictive value (NPV)(%) compared to the liver histopathology diagnosis: * Conventional Ultrasonography: Detects liver steatosis and evaluates liver size (cm), texture, and fibrosis.; * Shear-wave elastography (SWE): Measures liver stiffness(kPa), correlating with fibrosis severity (F0-F1: 0.0 - 8.27 kPa = Normal-mild, F2: 8.27 - 9.4 kPa = mild-moderate, F3: 9.4-11.8 kPa = moderate-severe, F4: \>11.8 kPa cirrhosis).; * Ultrasound-guided acoustic pulse (UGAP) examination: Combines ultrasound with acoustic pulses to assess liver steatosis by measuring the attenuation of ultrasound waves as they pass through the liver. Higher attenuation values generally correlate with a greater degree of hepatic steatosis (attenuation coefficient cutoff value (dB/cm/MHz): ≥S1= 0.65, ≥S2= 0.71, S3= 0.77).
Proteomic Changes and Their Correlation with MASLD Regression	At Baseline	This outcome measures changes in protein expression between MASLD-positive patients and a control of MASLD- negative patients. Both group will have equal number of participants, and equal male to female ratio.; Protein levels will be measured using liquid chromatography tandem mass spectrometry (counts per second (cps), and Changes in protein levels and will be quantified as percent and fold changes.; .
Accuracy of Available Formulae for MASLD Assessment	At Baseline, at 6-months after the surgery, and at 12 months after the surgery	To evaluate the diagnostic accuracy of three formulae for diagnosing MASLD by assessing Sensitivity(percentage), Specificity(percentage), Positive Predictive Value (PPV)(percentage), and Negative Predictive Value (NPV)(percentage) compared to the liver histopathology diagnosis.; 1. APRI: Uses AST levels (U/L) and platelet count (x10\^9/l) to estimate liver fibrosis risk (\< 0.5 = minimal or no fibrosis, 0.5 - 1.5 = Moderate fibrosis, \> 1.5 = Severe fibrosis or cirrhosis).; 2. FIB-4: Combines age(years), AST(U/L), ALT(U/L), and platelet count (x10\^9/l) to assess liver fibrosis risk (\< 1.45 = minimal or no fibrosis, 1.45 - 3.39 = significant fibrosis, ≥ 3.4 = advanced fibrosis or cirrhosis).; 3. NAFLD-Fibrosis Score: Uses age (years), BMI (kg/m\^2), diabetes status, liver enzymes (U/l), platelet count (x10\^9/l), and albumin (g/L) to assess fibrosis risk (\< -1.455 = low probability of fibrosis, -1.455- 0.765 = significant fibrosis, \> 0.675 = high probability of fibrosis).
mi-RNA Changes and Their Correlation with MASLD Regression and Diabetes Remission	At Baseline, at 6-months after the surgery, and at 12 months after the surgery	This outcome measures changes in circulating microRNA (miRNA) levels, in relation to diabetes remission post-bariatric surgery. Changes in miRNA levels will be quantified as percent and fold changes.; miRNA levels will be measured using micro-array technique. Changes will be assessed in the diabetic disease state and after achieving diabetes remission, defined by fasting glucose \<100 mg/dL and HbA1c \<6.5%.; miRNA changes will be correlated with diabetes remission at 6 and 12 months.

Secondary Outcome Measures

Name	Time	Method
Percentage of MASLD Regression Post-Bariatric Surgery	At 6-months after the surgery, and at 12 months after the surgery	This outcome aims to assess the regression of Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) after bariatric surgery. MASLD regression will be evaluated through changes in liver stiffness, liver enzymes, inflammatory markers, and MASLD risk scores: 1. Liver Stiffness (kPa): Measured by elastography. A decrease of at least 30% from baseline suggests regression.; 2. Liver Enzymes \[AST, ALT, ALP, GGT (U/L)\]: A significant decrease in enzyme levels indicates improved liver function.; 3. Inflammatory Markers: A reduction in inflammatory markers (e.g., CRP) signals MASLD improvement.; 4. MASLD Risk Scores: 1. FIB-4: A reduction in score suggests decreased fibrosis.; 2. APRI: A decrease indicates improved liver function.; 3. NAFLD-Fibrosis Score: A reduction suggests MASLD regression.; MASLD regression will be assessed at 6- and 12-months post-surgery, focusing on these markers and risk scores.
Percentage of Type 2 Diabetes Remission Post-Bariatric Surgery	At 6-months after the surgery, and at 12 months after the surgery	This outcome evaluates the remission of Type 2 Diabetes Mellitus (T2DM) following bariatric surgery. T2DM remission will be determined by changes in fasting glucose and glycated hemoglobin (HbA1c) levels: Fasting Glucose: Fasting glucose levels will be measured after an overnight fast. A fasting glucose level below 100 mg/dL will be considered indicative of T2DM remission.; Glycated Hemoglobin (HbA1c): HbA1c levels reflect average blood glucose over the past 2-3 months. T2DM remission is defined as an HbA1c level below 6.5% without the need for diabetes medications.; T2DM remission will be assessed at 6 and 12 months following bariatric surgery, with remission defined by meeting the aforementioned glucose and HbA1c thresholds.
Excess Weight Loss (EWL) Measurement	At Baseline, at 6-months after the surgery, and at 12 months after the surgery	This outcome assesses the effectiveness of bariatric surgery in terms of Excess Weight Loss (EWL). EWL will be calculated based on individual measurements of weight and ideal body weight.; 1. Pre-surgery Weight (kg): Weight will be measured before surgery.; 2. Post-surgery Weight (kg): Weight will be measured at 6 and 12 months.; 3. Ideal Body Weight (kg): Ideal body weight (IBW) will be calculated using one of the following formulae based on patients' gender: For Men: IBW (kg) = 50 + 0.91 × (height in cm - 152.4); For Women: IBW (kg) = 45.5 + 0.91 × (height in cm - 152.4); 4. Excess Weight Loss (EWL): EWL will be calculated as: EWL (%) = \[(Pre-surgery weight - Ideal body weight) / (Pre-surgery weight - post-surgery weight)\] × 100; 5. Statistical Analysis: Paired t-tests will compare pre- and post-surgery weight. Regression models will assess factors affecting EWL and its link to clinical outcomes.
Body Composition Parameters After Bariatric Surgery	At baseline, and at 6 months and 12 months after bariatric surgery	The body composition is measured using Bioelectrical Impedance Analysis (BIA) device to assess the proportions of fat, muscle, bone, and water in the body.; The following parameters are measured at baseline, and then at 6 and 12 months after bariatric surgery: Weight (kg), Height (m),BMI (kg/m\^2), Fat Mass (kg), Fat Free Mass (kg), Fat Percentage (%), Bone Mass (kg), Muscle Mass (kg), Total Body Water (kg), Intracellular Water (kg), Extracellular water (kg), Visceral Fat Rating, Metabolic age (years); All parameters are measured using a fully-automated BIA scales.

Trial Locations

Locations (2)

Alhakeem Radiology Center; 🇧🇭 Manama, Manama, Bahrain

King Hamad University Hospital; 🇧🇭 Al Muharraq, Muharraq, Bahrain