Evaluating Non-Invasive Approaches for Screening, Diagnosis, and Monitoring of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Bariatric Patients & Identifying Biomarkers for Predicting Type 2 Diabetes Remission
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 163
- 试验地点
- 2
- 主要终点
- Accuracy of Non-invasive Ultrasonography Tools for MASLD Assessment
研究概览
简要总结
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.
详细描述
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:
- Anthropometric Measures including weight, hight, body mass index, etc.
- Body composition data including fat mass, muscle mass, etc.
- Routine bariatric profile blood results including liver enzymes, platelets, etc.
- Abdominal ultrasonography reports.
- Shear wave elastography radiological assessment
- Proteomic and transcriptomic profiling outside Bahrain
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult obese patients undergoing bariatric surgery in KHUH surgery department consented to be included in the study.
排除标准
- •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/m
- •Post-liver transplant patients
- •Patients known to have any liver disease other than MASLD
- •Patients with history of Alcohol Drinking.
结局指标
主要结局
Accuracy of Non-invasive Ultrasonography Tools for MASLD Assessment
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Percentage of MASLD Regression Post-Bariatric Surgery(At 6-months after the surgery, and at 12 months after the surgery)
- Percentage of Type 2 Diabetes Remission Post-Bariatric Surgery(At 6-months after the surgery, and at 12 months after the surgery)
- Excess Weight Loss (EWL) Measurement(At Baseline, at 6-months after the surgery, and at 12 months after the surgery)
- Body Composition Parameters After Bariatric Surgery(At baseline, and at 6 months and 12 months after bariatric surgery)