Quantitative Detection Efficiency of UDFF for Nonalcoholic Fatty Liver Disease

Non-alcoholic Fatty Liver Disease Clinical Trial

— UDFF  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05802199
• Other study ID #: CHESS2303
• Status: Recruiting
• Start date: January 1, 2023
• Est. completion date: December 31, 2023

Study information

• Verified date: March 2023
• Source: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Contact: Xiaolong Qi, M.D.
• Phone: +8618588602600
• Email: qixiaolong[@]vip.163.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. be at least 18 years of age.

2. fulfilled diagnosis of non-alcoholic fatty liver disease based on radiological (MRI-PDFF values > 5%) and clinical manifestation.

3. fulfilled diagnosis of hepatic fibrosis with non-alcoholic fatty liver disease based on radiological (LSM by MRE > 3.02kPa) and clinical manifestation.

4. Willing to participate in this research and sign the informed consent.

Exclusion Criteria:

1. with liver dysfunction at the terminal stage or are ready for liver transplantation.

2. with viral hepatitis, autoimmune hepatitis, and alpha-1-antitrypsin deficiency.

3. 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).

4. unable to cooperate with ultrasound examinations.

5. have taken liver damage drugs within the past six months.

6. with massive ascites.

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease

Intervention

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.

Locations

Country	Name	City	State
China	The People's Hospital of Bozhou	Bozhou	Anhui
China	The First Bethune Hospital of Jilin University	Changchun	Jilin
China	Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The Second Hospital of Anhui Medical University	Hefei	Anhui
China	Shandong Public Health Clinical Center	Jinan	Shandong
China	Lishui People's Hospital	Lishui	Zhejiang
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Zhongda Hospital, Southeast University	Nanjing	Jiangsu
China	Xinhua Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	Zhe Third People's Hospital of Zhenjiang	Zhenjiang	Jiangsu
Switzerland	Kliniken Hirslanden Beau Site, Salem und Permancence	Bern	Kanton Bern

Sponsors (14)

Lead Sponsor

Collaborator

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

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

Countries where clinical trial is conducted

China,  Switzerland, 

References & Publications (13)

Chitturi S, Farrell GC, Hashimoto E, Saibara T, Lau GK, Sollano JD; Asia-Pacific Working Party on NAFLD. Non-alcoholic fatty liver disease in the Asia-Pacific region: definitions and overview of proposed guidelines. J Gastroenterol Hepatol. 2007 Jun;22(6) — View Citation

Dasarathy S, Dasarathy J, Khiyami A, Joseph R, Lopez R, McCullough AJ. Validity of real time ultrasound in the diagnosis of hepatic steatosis: a prospective study. J Hepatol. 2009 Dec;51(6):1061-7. doi: 10.1016/j.jhep.2009.09.001. Epub 2009 Sep 20. — View Citation

European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty live — View Citation

Ferraioli G, Berzigotti A, Barr RG, Choi BI, Cui XW, Dong Y, Gilja OH, Lee JY, Lee DH, Moriyasu F, Piscaglia F, Sugimoto K, Wong GL, Wong VW, Dietrich CF. Quantification of Liver Fat Content with Ultrasound: A WFUMB Position Paper. Ultrasound Med Biol. 20 — View Citation

Gao J, Wong C, Maar M, Park D. Reliability of performing ultrasound derived SWE and fat fraction in adult livers. Clin Imaging. 2021 Dec;80:424-429. doi: 10.1016/j.clinimag.2021.08.025. Epub 2021 Sep 17. — View Citation

Hernaez R, Lazo M, Bonekamp S, Kamel I, Brancati FL, Guallar E, Clark JM. Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis. Hepatology. 2011 Sep 2;54(3):1082-1090. doi: 10.1002/hep.24452. — View Citation

Kim SH, Lee JM, Kim JH, Kim KG, Han JK, Lee KH, Park SH, Yi NJ, Suh KS, An SK, Kim YJ, Son KR, Lee HS, Choi BI. Appropriateness of a donor liver with respect to macrosteatosis: application of artificial neural networks to US images--initial experience. Ra — View Citation

Labyed Y, Milkowski A. Novel Method for Ultrasound-Derived Fat Fraction Using an Integrated Phantom. J Ultrasound Med. 2020 Dec;39(12):2427-2438. doi: 10.1002/jum.15364. Epub 2020 Jun 11. — View Citation

Marshall RH, Eissa M, Bluth EI, Gulotta PM, Davis NK. Hepatorenal index as an accurate, simple, and effective tool in screening for steatosis. AJR Am J Roentgenol. 2012 Nov;199(5):997-1002. doi: 10.2214/AJR.11.6677. — View Citation

Sanyal AJ, Brunt EM, Kleiner DE, Kowdley KV, Chalasani N, Lavine JE, Ratziu V, McCullough A. Endpoints and clinical trial design for nonalcoholic steatohepatitis. Hepatology. 2011 Jul;54(1):344-53. doi: 10.1002/hep.24376. — View Citation

Simon TG, Roelstraete B, Khalili H, Hagstrom H, Ludvigsson JF. Mortality in biopsy-confirmed nonalcoholic fatty liver disease: results from a nationwide cohort. Gut. 2021 Jul;70(7):1375-1382. doi: 10.1136/gutjnl-2020-322786. Epub 2020 Oct 9. — View Citation

Webb M, Yeshua H, Zelber-Sagi S, Santo E, Brazowski E, Halpern Z, Oren R. Diagnostic value of a computerized hepatorenal index for sonographic quantification of liver steatosis. AJR Am J Roentgenol. 2009 Apr;192(4):909-14. doi: 10.2214/AJR.07.4016. — View Citation

Zhang MH, Li J, Zhu XY, Zhang YQ, Ye ST, Leng YR, Yang T, Zhang H, Kong LY. Physalin B ameliorates nonalcoholic steatohepatitis by stimulating autophagy and NRF2 activation mediated improvement in oxidative stress. Free Radic Biol Med. 2021 Feb 20;164:1-1 — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The efficiency of UDFF (in %) for hepatic steatosis in comparison with MRI-PDFF (in %).	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.	1 years
Secondary	The efficiency of auto-pSWE (in kPa) for hepatic fibrosis in comparison with MRE (in kPa).	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.	1 years