Quantitative Detection Efficiency of UDFF for Nonalcoholic Fatty Liver Disease

Sponsor

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine (Other)

Overall Status

Recruiting

CT.gov ID

NCT05802199

Collaborator

Zhongda Hospital (Other), Zhejiang University (Other), Lishui Country People's Hospital (Other), Shandong Public Health Clinical Center (Other), Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine (Other), First Affiliated Hospital of Wenzhou Medical University (Other), The First Affiliated Hospital with Nanjing Medical University (Other), The Second Hospital of Anhui Medical University (Other), The People's Hospital of Bozhou (Other), The First Affiliated Hospital of Xiamen University (Other), The First Hospital of Jilin University (Other), Kliniken Hirslanden Beau Site, Salem und Permancence (Other), Third People's Hospital of Zhenjiang, Jiangsu University (Other)

300

Enrollment

Locations

Anticipated Duration (Months)

21.4

Patients Per Site

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, affecting more than 25 % of the population globally. Approximately 20 % - 25 % of NAFLD patients can develop nonalcoholic steatohepatitis (NASH), which leads to more rapid progression from fibrosis to cirrhosis, and even liver failure or hepatocellular carcinoma (HCC). Early detection and treatment may halt or reverse NAFLD progression.

Although liver biopsy has been the well-accepted clinical reference standard for both diagnosis and staging of the different histological changes in NAFLD, this procedure is invasive with complications such as bleeding and infection, and is unreliable for quantifying steatosis due to sampling errors. Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) currently has been accepted as the preferred alternative to the histological assessment of hepatic steatosis in patients with NAFLD. Magnetic resonance elastography (MRE) provide additional information of inflammation and fibrotic components of NAFLD. However, important limitations hinder the widespread clinical application of MRI, including high cost, low availability, long scan times and exclusion of patients with metal implants.

Ultrasound (US) has been recommended by several guidelines as the first-line screening tool for patients at risk of NAFLD. The developed ultrasound-derived fat fraction (UDFF) is designed to assess hepatic steatosis by estimating the frequency-dependent attenuation coefficient (AC) and backscatter coefficient (BSC) through processing acoustic radiofrequency (RF) signals returned from the liver tissue as fat vesicles in hepatocytes have a different characteristic impedance compared to normal liver tissue. UDFF is available on the Acuson Sequoia ultrasound system (Simens Healthineers, Mountain View, CA, USA), with reference to integrated phantom data to correct for system impact, and produces a UDFF value presented as a fat fraction (%), which is potentially related to MRI-PDFF and can be directly compared with MRI-PDFF. In addition, automatic point shear wave elastography (auto-pSWE) is available on the Acuson Sequoia ultrasound system to obtain liver stiffness measurement (LSM) for assessing hepatic fibrosis, simultaneously with UDFF measurement. The prospective, multicenter study aims to evaluate the efficiency of UDFF as a quantitative non-invasive alternative for NAFLD.

Condition or Disease	Intervention/Treatment	Phase
Non-alcoholic Fatty Liver Disease	Diagnostic Test: Hepatic fat fraction and hepatic fibrosis

Detailed Description

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide characterized by excessive accumulation of triglycerides in hepatocytes and subsequent steatosis, affecting more than 25 % of the population globally. Approximately 20 % - 25 % of NAFLD patients can develop nonalcoholic steatohepatitis (NASH), which leads to more rapid progression from fibrosis to cirrhosis, and even liver failure or hepatocellular carcinoma (HCC). NALFD is strongly associated with metabolic risk factors, such as obesity, cardiovascular disease, and diabetes mellitus. Early detection and treatment may halt or reverse NAFLD progression. However, the occurrence and progression of steatosis and fibrosis had no obvious clinical symptoms, resulting in a difficulty of early diagnose and grade individuals with NAFLD clinically.

Although liver biopsy has been the well-accepted clinical reference standard for both diagnosis and staging of the different histological changes in NAFLD, this procedure is invasive with complications such as bleeding and infection, and is unreliable for quantifying steatosis due to sampling errors. Several imaging modalities have been used to diagnose and grade hepatic steatosis. Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) currently has been accepted as the preferred alternative to the histological assessment of hepatic steatosis in patients with NAFLD. Magnetic resonance elastography (MRE) provide additional information of inflammation and fibrotic components of NAFLD. However, important limitations hinder the widespread clinical application of MRI, including high cost, low availability, long scan times and exclusion of patients with metal implants.

Ultrasound (US) has been recommended by several guidelines as the first-line screening tool for patients at risk of NAFLD. The most commonly used noninvasive method that quantifies the amount of fat in the liver is the controlled attenuation parameter, and more than 10% of steatosis can be distinguished. The disadvantages of this technique are that the liver morphological changes cannot be assessed simultaneously and poor performance in patients with higher body mass indices, leading to a failure rate of measurement ranged of 7.7 % - 14.0 %.

The developed ultrasound-derived fat fraction (UDFF) is designed to assess hepatic steatosis by estimating the frequency-dependent attenuation coefficient (AC) and backscatter coefficient (BSC) through processing acoustic radiofrequency (RF) signals returned from the liver tissue as fat vesicles in hepatocytes have a different characteristic impedance compared to normal liver tissue. UDFF is available on the Acuson Sequoia ultrasound system (Simens Healthineers, Mountain View, CA, USA), with reference to integrated phantom data to correct for system impact, and produces a UDFF value presented as a fat fraction (%), which is potentially related to MRI-PDFF and can be directly compared with MRI-PDFF. In addition, automatic point shear wave elastography (auto-pSWE) is available on the Acuson Sequoia ultrasound system to obtain liver stiffness measurement (LSM) for assessing hepatic fibrosis, simultaneously with UDFF measurement. The prospective, multicenter study aims to evaluate the efficiency of UDFF as a quantitative non-invasive alternative for NAFLD.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

300 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Quantitative Detection Efficiency of Ultrasound Derived Fat Fraction (UDFF) as a Non-invasive Alternative for Nonalcoholic Fatty Liver Disease (CHESS2303): a Multicenter Prospective Study

Actual Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Training cohort Patients were fulfilled diagnosis of non-alcoholic fatty liver disease based on radiological and clinical manifestation. Patients were fulfilled diagnosis of hepatic fibrosis based on radiological and clinical manifestation.	Diagnostic Test: Hepatic fat fraction and hepatic fibrosis All patients underwent measurement of UDFF for hepatic fat fraction and auto-pSWE for hepatic fibrosis. All patients underwent measurement of MRI-PDFF for hepatic fat fraction and MRE for hepatic fibrosis as reference standard.
Validation cohort Patients were fulfilled diagnosis of non-alcoholic fatty liver disease based on radiological and clinical manifestation. Patients were fulfilled diagnosis of hepatic fibrosis based on radiological and clinical manifestation.	Diagnostic Test: Hepatic fat fraction and hepatic fibrosis All patients underwent measurement of UDFF for hepatic fat fraction and auto-pSWE for hepatic fibrosis. All patients underwent measurement of MRI-PDFF for hepatic fat fraction and MRE for hepatic fibrosis as reference standard.

Arm

Intervention/Treatment

Training cohort

Patients were fulfilled diagnosis of non-alcoholic fatty liver disease based on radiological and clinical manifestation. Patients were fulfilled diagnosis of hepatic fibrosis based on radiological and clinical manifestation.

Diagnostic Test: Hepatic fat fraction and hepatic fibrosis

All patients underwent measurement of UDFF for hepatic fat fraction and auto-pSWE for hepatic fibrosis. All patients underwent measurement of MRI-PDFF for hepatic fat fraction and MRE for hepatic fibrosis as reference standard.

Validation cohort

Diagnostic Test: Hepatic fat fraction and hepatic fibrosis

Outcome Measures

Primary Outcome Measures

The efficiency of UDFF (in %) for hepatic steatosis in comparison with MRI-PDFF (in %). [1 years]
Evaluate the diagnosis performance of ultrasound-derived fat fraction (UDFF) as a quantitative non-invasive alternative for diagnosing and grading of hepatic steatosis in NAFLD patients, taking MRI-PDFF as the reference standard.

Secondary Outcome Measures

The efficiency of auto-pSWE (in kPa) for hepatic fibrosis in comparison with MRE (in kPa). [1 years]
Evaluate the diagnosis performance of auto-pSWE as a quantitative non-invasive alternative for diagnosing and grading of hepatic fibrosis in NAFLD patients, taking MRE as the reference standard.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

be at least 18 years of age.
fulfilled diagnosis of non-alcoholic fatty liver disease based on radiological (MRI-PDFF values > 5%) and clinical manifestation.
fulfilled diagnosis of hepatic fibrosis with non-alcoholic fatty liver disease based on radiological (LSM by MRE > 3.02kPa) and clinical manifestation.
Willing to participate in this research and sign the informed consent.

Exclusion Criteria:

with liver dysfunction at the terminal stage or are ready for liver transplantation.
with viral hepatitis, autoimmune hepatitis, and alpha-1-antitrypsin deficiency.
history of excessive drinking (the amount of alcohol consumed by women is more than 140 grams per week, and that of men is more than 210 grams per week).
unable to cooperate with ultrasound examinations.
have taken liver damage drugs within the past six months.
with massive ascites.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The People's Hospital of Bozhou	Bozhou	Anhui	China	236000
2	The Second Hospital of Anhui Medical University	Hefei	Anhui	China	230601
3	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian	China	361000
4	Zhongda Hospital, Southeast University	Nanjing	Jiangsu	China	210000
5	Jiangsu Province Hospital	Nanjing	Jiangsu	China
6	Zhe Third People's Hospital of Zhenjiang	Zhenjiang	Jiangsu	China	212021
7	The First Bethune Hospital of Jilin University	Changchun	Jilin	China	130000
8	Shandong Public Health Clinical Center	Jinan	Shandong	China	250000
9	Xinhua Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai	China	200000
10	Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang	China	310000
11	Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang	China	310000
12	Lishui People's Hospital	Lishui	Zhejiang	China	323000
13	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang	China	325000
14	Kliniken Hirslanden Beau Site, Salem und Permancence	Bern	Kanton Bern	Switzerland	200032

Sponsors and Collaborators

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Zhongda Hospital
Zhejiang University
Lishui Country People's Hospital
Shandong Public Health Clinical Center
Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine
First Affiliated Hospital of Wenzhou Medical University
The First Affiliated Hospital with Nanjing Medical University
The Second Hospital of Anhui Medical University
The People's Hospital of Bozhou
The First Affiliated Hospital of Xiamen University
The First Hospital of Jilin University
Kliniken Hirslanden Beau Site, Salem und Permancence
Third People's Hospital of Zhenjiang, Jiangsu University

Investigators

Study Chair: Jiangao Fan, M.D., Xinhua Hospital, Shanghai Jiaotong University School of Medicine
Principal Investigator: Xiaolong Qi, M.D., Zhongda Hospital
Study Director: Yi Dong, M.D., Xinhua Hospital, Shanghai Jiaotong University School of Medicine