Monitoring Changes in Hepatic Steatosis During a Lifestyle Intervention Programme in Patients With Non-alcoholic Fatty Liver Disease Using the Novel Continuous Controlled Attenuation Parameter Versus MRI Proton Density Fat Fraction
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 2
- 主要终点
- MRI-PDFF response
研究概览
简要总结
Background: Non-alcoholic fatty liver disease (NAFLD) affects 30% of the Asian adult population and is emerging as one of the important leading causes of liver cancer and cirrhosis. Although a number of biomarkersmany have been developed for the assessment of liver fat and fibrosis, most existing studies were cross-sectional in nature. The role of these biomarkers for monitoring and response assessment remains elusive. At present, magnetic resonance imaging proton density fat fraction (MRI-PDFF) is considered the gold standard to in quantifying liver fat. The MRI-PDFF response, defined as a ≥30% relative reduction in liver fat fraction, has been shown to correlate with improved hepatic inflammation and fibrosis. However, MRI is limited by cost and availability. The cContinuous controlled attenuation parameter (CAPc) measurement by vibration controlled transient elastography is a new technology to quantify liver fat. It is a point-of-care test and has the potential to replace the MRI-PDFF as a monitoring and response biomarker in routine practice.
Study plan: This prospective cohort study will include 150 patients with NAFLD who will join a 6-month lifestyle modification programme involving dietary intervention and physical training. This will create a cohort of varying degrees of liver fat reduction. Using MRI-PDFF as the reference standard, we will evaluate the accuracy of a changes in CAPc in reflecting the MRI-PDFF response and remission of NAFLD, with all non-invasive tests performed at screening and Month 6. In addition, we will test the hypothesis that the the change in CAPc is superior to the change of in other steatosis tests results (including the original CAP, abdominal ultrasonography and steatosis scores of fatty liver index, hepatic steatosis index, NAFLD liver fat score and NAFLD ridge score) in predicting the MRI-PDFF response. The area under the receiver-operating characteristics curve of the CAPc response in predicting the MRI-PDFF response will be compared with that of the other steatosis tests using the DeLong test.
详细描述
STUDY DESIGN OVERVIEW In order to evaluate the use of continuous CAP to monitor changes in liver fat over time, we need a cohort of patients with varying degree of liver fat reduction. Therefore, we will enrol MASLD patients in a lifestyle intervention programme. With this design, we will measure original CAP, continuous CAP and MRI-PDFF in all patients at baseline and Month 6. As described in the introduction, MRI-PDFF is an accurate and reliable non-invasive test to quantify liver fat and will serve as the reference standard in this study.
- CLINIC VISITS AND ASSESSMENTS Clinic visits The patients will attend 4 clinic visits (screening, baseline, month 3 and month 6).
Procedures at the screening visit
- Obtain informed written consent
- Verify conformance with the study inclusion and exclusion criteria
- Record medical history
- Record smoking and alcohol consumption with standard questionnaires
- Physical examination
- Blood tests including complete blood count, prothrombin time, renal function test and liver biochemistry (including alanine aminotransferase [ALT], aspartate aminotransferase [AST] and gamma-glutamyl transpeptidase [GGT]), lipids, plasma glucose and HbA1c.
- Hepatitis B surface antigen and anti-hepatitis C virus antibody
- Vibration-controlled transient elastography examination
- Bedside abdominal ultrasonography. The diagnosis of fatty liver will be based on the presence of bright liver echotexture, deep attenuation of ultrasound signal and blurring of hepatic vasculature.(19)
- Arrange MRI-PDFF examination within 1 week of VCTE examination. The short interval is to avoid significant change in liver fat between the non-invasive measurements of liver fat by original CAP, continuous CAP and MRI-PDFF.
Procedures at the baseline visit
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Intrahepatic triglyceride content by MRI-PDFF ≥5%
- •At least one metabolic risk factor out of (1) body-mass index ≥23 kg/m2, (2) waist circumference ≥90 cm in men and ≥80 cm in women, (3) fasting plasma glucose ≥5.6 mmol/L, 2-hour post-load glucose ≥7.8 mmol/L, haemoglobin A1c (HbA1c) ≥5.7%, known diabetes or on treatment for type 2 diabetes, (4) blood pressure ≥130/85 mmHg or on treatment for hypertension, (5) plasma triglycerides ≥1.7 mmol/L or on treatment for dyslipidaemia, and (6) plasma high-density lipoprotein-cholesterol ≤1.0 mmol/L in men and ≤1.3 mmol/L in women or on treatment for dyslipidaemia
- •Provide informed written consent
排除标准
- •Positive hepatitis B surface antigen or anti-hepatitis C virus antibody, or history or evidence of other liver diseases
- •Alcohol consumption >30 g per day in men or >20 g per day in women
- •Liver decompensation, as evidenced by total bilirubin >50 µmol/L (except in patients with documented Gilbert's syndrome), platelet count <100 x 109/L, prothrombin time >1.3 times the upper limit of normal, albumin <35 g/L, or history or presence of ascites, varices or hepatic encephalopathy
- •Contraindications to MRI examination such as claustrophobia or the presence of metallic implants
- •History or presence of hepatocellular carcinoma
- •History of other malignancies, unless in complete remission for more than 5 years
- •History of liver transplantation or liver resection
- •Significant co-morbidities that will likely limit a patient's participation in lifestyle intervention or attendance of study follow-ups
结局指标
主要结局
MRI-PDFF response
时间窗: 6 months
\>30% relative reduction in MRI-PDFF
次要结局
- Remission of MASLD(6 months)
研究者
Vincent WS Wong
Professor
Chinese University of Hong Kong