NCT05802199

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.

Trial Health

47
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
300

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Jan 2023

Shorter than P25 for all trials

Geographic Reach
2 countries

14 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2023

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

March 14, 2023

Completed
23 days until next milestone

First Posted

Study publicly available on registry

April 6, 2023

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2023

Completed
Last Updated

April 10, 2023

Status Verified

March 1, 2023

Enrollment Period

12 months

First QC Date

March 14, 2023

Last Update Submit

April 6, 2023

Conditions

Keywords

non-alcoholic fatty liver disease (NAFLD)ultrasound-derived fat fraction (UDFF)hepatic fibrosispoint shear wave elastography

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (1)

  • The efficiency of auto-pSWE (in kPa) for hepatic fibrosis in comparison with MRE (in kPa).

    1 years

Study Arms (2)

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

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

Interventions

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.

Training cohortValidation cohort

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

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

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

The People's Hospital of Bozhou

Bozhou, Anhui, 236000, China

NOT YET RECRUITING

The Second Hospital of Anhui Medical University

Hefei, Anhui, 230601, China

NOT YET RECRUITING

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, 361000, China

NOT YET RECRUITING

Zhongda Hospital, Southeast University

Nanjing, Jiangsu, 210000, China

RECRUITING

Jiangsu Province Hospital

Nanjing, Jiangsu, China

NOT YET RECRUITING

Zhe Third People's Hospital of Zhenjiang

Zhenjiang, Jiangsu, 212021, China

NOT YET RECRUITING

The First Bethune Hospital of Jilin University

Changchun, Jilin, 130000, China

NOT YET RECRUITING

Shandong Public Health Clinical Center

Jinan, Shandong, 250000, China

NOT YET RECRUITING

Xinhua Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

NOT YET RECRUITING

Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

NOT YET RECRUITING

Lishui People's Hospital

Lishui, Zhejiang, 323000, China

NOT YET RECRUITING

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, 325000, China

NOT YET RECRUITING

Kliniken Hirslanden Beau Site, Salem und Permancence

Bern, Canton of Bern, 200032, Switzerland

NOT YET RECRUITING

Related Publications (13)

  • 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. 2021 Oct;47(10):2803-2820. doi: 10.1016/j.ultrasmedbio.2021.06.002. Epub 2021 Jul 18.

  • 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.

  • 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.

  • 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;164:1-12. doi: 10.1016/j.freeradbiomed.2020.12.020. Epub 2021 Jan 1.

  • 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):778-87. doi: 10.1111/j.1440-1746.2007.05001.x.

  • 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 liver disease. Diabetologia. 2016 Jun;59(6):1121-40. doi: 10.1007/s00125-016-3902-y. No abstract available.

  • 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. Radiology. 2005 Mar;234(3):793-803. doi: 10.1148/radiol.2343040142. Epub 2005 Jan 21.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

MeSH Terms

Conditions

Non-alcoholic Fatty Liver DiseaseLiver Cirrhosis

Condition Hierarchy (Ancestors)

Fatty LiverLiver DiseasesDigestive System DiseasesFibrosisPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Jiangao Fan, M.D.

    Xinhua Hospital, Shanghai Jiaotong University School of Medicine

    STUDY CHAIR
  • Xiaolong Qi, M.D.

    Zhongda Hospital

    PRINCIPAL INVESTIGATOR
  • Yi Dong, M.D.

    Xinhua Hospital, Shanghai Jiaotong University School of Medicine

    STUDY DIRECTOR

Central Study Contacts

Xiaolong Qi, M.D.

CONTACT

Yunlin Huang, M.D.

CONTACT

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Target Duration
1 Year
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 14, 2023

First Posted

April 6, 2023

Study Start

January 1, 2023

Primary Completion

December 31, 2023

Study Completion

December 31, 2023

Last Updated

April 10, 2023

Record last verified: 2023-03

Locations