Clinical trial NCT02476695: FibroTouch Non-invasive Evaluation of Liver Fibrosis and Cirrhosis
Official title: Research on FibroTouch Noninvasive Evaluation of Liver Fibrosis and Cirrhosis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Liver Fibrosis
Cirrhosis
Chronic Hepatitis B
Keywords: CHB
Lead sponsor: Wuxi Hisky Medical Technology Co Ltd
Sponsor class: INDUSTRY
Collaborators: name: Beijing Friendship Hospital
name: The Military General Hospital of Beijing, PLA
name: The First Affiliated Hospital, Third Military University
name: The First Affiliated Hospital of the Fourth Military Medical University
name: The First Hospital of Jilin University
name: Hebei Medical University Third Hospital
name: Henan Provincial People's Hospital
name: Jiangsu Provincial People's Hospital
name: Ruijin Hospital
name: West China Hospital
name: Tianjin Third Central Hospital
name: No.85 Hospital, Changning, Shanghai, China
name: Third Affiliated Hospital, Sun Yat-Sen University
name: Hospital of Chinese Medicine of the Xinjiang Uygur Autonomous Region
name: The China-Japan Friendship Hospital
name: Peking University Clinical Research Institute (PUCRI)
First posted: 2015-06-19
Enrollment: 412
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The subjects with chronic hepatitis B (CHB), who underwent a liver biopsy in hospital and meets all of the inclusion criteria and none of the exclusion criteria, may participate in this study. Within three months of FibroTouch examination, subjects are required to have qualified histological specimens of liver biopsy for analysis and comparison.

Brief summary: This prospective and multicenter study is to determine the diagnostic performance (accuracy, specificity and sensitivity) of transient elastography (FibroTouch) for liver fibrosis assessment in chronic hepatitis B (CHB) patients using ROC analysis, and liver biopsy as the reference.

Actual 517 patients will be enrolled to guarantee 500 final statistical cases; and ≥100 cases are required for fibrosis stage S0/1, S2, S3 and S4 (compensatory stage of cirrhosis), respectively. For each stage, the case is assigned as equally as possible.

Detailed description: The liver diseases frequently occur in China. For various reasons, the chronic liver diseases are not controlled in time, and then develop gradually into liver fibrosis and cirrhosis. Without effective treatment, the advanced liver cirrhosis seriously influences the quality of patients' life, and places an intolerable burden on family and society. At present, the scholars generally thought that the liver fibrosis at early stages is reversible. Therefore, if the liver fibrosis in patients with chronic liver diseases can be accurately evaluated at early stages and be treated in time, so we can stop the progress of diseases and reduce the occurrence of liver cirrhosis and liver cancer.

For many years, liver biopsy is still as "golden standard" for diagnosis of liver inflammation and fibrosis. However, with its invasiveness, potential risks and some complications, liver biopsy is limited in clinical application due to the poor acceptability and repeatability. In recent years, the liver fibrosis cannot directly and accurately diagnose via the various diagnostic models using serological biomarkers (e.g. FIBROTEST and APRI) and medical imaging technologies (e.g. ultrasonic B, CT and MRI).

Transient elastography is a new technology in the field of ultrasonic imaging. Liver stiffness measurement (LSM) is based on the relationship between the speed of spread of acoustic wave in tissues and stiffness of the tissues. It utilizes specific probes to send out controlled low-frequency shear waves, the waves signals transmit through liver tissues, a high-frequency signals will track the transmitting process of shear wave in the liver and the value of liver stiffness (kPa) is quickly calculated with reference to a built-in liver histological model, which provides a quantitative standard for diagnosis of liver fibrosis of chronic liver disease. The bigger LSM value means the faster transmission of shear wave, and the harder of determined liver tissue.

As stated in the "12th Five-year Plan for Medical Device Technological Industry" (the Ministry of Science and Technology), China will greatly support the research and development of new medical devices and promote the application of Chinese transient elastography system, FibroTouch, which was R\&D by Tsing-Hua University independently with new algorithm. FibroTouch can rapidly determine the LSM in a non-invasive way and provide useful information for liver fibrosis and steatosis staging.

Due to FibroTouch is a new transient elastography system in marketing, there is no too much studies on the correlation between FibroTouch and liver biopsy in diagnosis of liver fibrosis and cirrhosis.

The goal of this prospective and multicenter study is to determine the diagnostic performance (accuracy, specificity and sensitivity) of FibroTouch for liver fibrosis assessment in chronic hepatitis B (CHB) patients using ROC analysis, and liver biopsy as the reference.

Actual 517 patients will be enrolled to guarantee 500 final statistical cases; and ≥100 cases are required for fibrosis stage S0/1, S2, S3 and S4 (compensatory stage of cirrhosis), respectively. For each stage, the case is assigned as equally as possible.

Eligibility criteria: Inclusion Criteria:

* Subjects with age 18-65 years, both gender
* Subjects with history of HBV or HBsAg positive \> 6 months up to enrollment
* Subjects with qualified liver biopsy specimens within three months (before or after) of Fibrotouch examination for pathological staging
* Subjects without chemical therapy history of powerful medicine to lower enzyme in the two weeks before blood biochemistry tests (e.g. dimethyl diphenyl bicarboxylate and bicyclol)
* Subjects must agree and sign the informed consent form

Exclusion Criteria:

* Subjects who are unable or unwilling to sign informed consent form
* Subjects who have merger of hepatitis C, alcohol and non-alcoholic fatty liver diseases, autoimmune liver diseases, inherited metabolic liver diseases, biliary systemic diseases or liver and gall parasitic diseases
* Subjects who have other serious chronic disorders or history of malignancy
* Subjects with ALT ≥5 ULN in the past 1 month
* Subjects with WBC\<3.5×10\^9/L, PLT\<60×10\^9/L, PTA\<60%
* Subjects with DBIL≥1.5 ULN
* Subjects with decompensated cirrhosis (especially the people with ascites)
* Pregnant or lactating women, or women who has a pregnant plan and don't want to birth control in the study period
* Subjects who have wound on the right upper abdomen recently
* Subjects who have various space-occupying tumor or cyst in right liver
* Subjects who have none or limited legal capacity

Primary outcomes:
measure: The Clinical Value Evaluation of FibroTouch for Non-invasive Diagnosis of Liver Fibrosis in Patients With Chronic Hepatitis B by Using Liver Pathology as the Gold Standard for Judging CHB Liver Fibrosis Stage
timeFrame: Participants will be offered a FibroTouch examination before or after taking the test of liver biopsy, and the time interval should not exceed 3 months.
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
city: Beijing
country: China
facility: The China-Japan Friendship Hospital
city: Beijing
country: China
facility: The Military General Hospital of Beijing, PLA
city: Changchun
country: China
facility: The First Bethune Hospital of Jilin University
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Chongqing
country: China
facility: The First Affiliated Hospital, Third Military University
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Sun Yat-Sen University
city: Nanjing
country: China
facility: Jiangsu Provincial People's Hospital
city: Shanghai
country: China
facility: No.85 Hospital of the PLA
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
city: Shijiazhuang
country: China
facility: The Third Hospital, Hebei Medical University
city: Tianjin
country: China
facility: Tianjin Third Central Hospital
city: Urumqi
country: China
facility: Hospital of Chinese Medicine of the Xinjiang Uygur Autonomous Region
city: Xi'an
country: China
facility: The First Affiliated Hospital, Fourth Military University
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
Study officials:
affiliation: Beijing Friendship Hospital
name: Jidong JIA, MD
role: STUDY_CHAIR
affiliation: The Military General Hospital of Beijing, PLA
name: Jianbiao CAO, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital, Third Military University
name: Qing MAO, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of the Fourth Military Medical University
name: Ying HAN, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Hospital of Jilin University
name: Junqi NIU, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hebei Medical University Third Hospital
name: Yuemin NAN, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Henan Provincial People's Hospital
name: JIA SHANG, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Jiangsu Provincial People's Hospital
name: Jun LI, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ruijin Hospital
name: Qing XIE, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: West China Hospital
name: Hong TANG, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tianjin Third Central Hospital
name: Tao HAN, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: No.85 Hospital, Changning, Shanghai, China
name: Qingchun FU, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Third Affiliated Hospital, Sun Yat-Sen University
name: Zhiliang GAO, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital of Chinese Medicine of the Xinjiang Uygur Autonomous Region
name: Xiaozhong WANG, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The China-Japan Friendship Hospital
name: Anlin MA, MD
role: PRINCIPAL_INVESTIGATOR
References: