FibroTouch Non-invasive Evaluation of Liver Fibrosis and Cirrhosis

Study Overview
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Brief Summary
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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. Approximately 600 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
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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. Approximately 600 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.

Official Title
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Research on FibroTouch Noninvasive Evaluation of Liver Fibrosis and Cirrhosis

Conditions
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Liver Fibrosis, Cirrhosis, Chronic Hepatitis B

Intervention / Treatment
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* Device: FibroTouch Examination
* Device: FibroScan Examination
* Device: Ultrasonic B Examination


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| S0/1<br>S0 = no fibrosis and S1 = portal fibrosis without septa | Device: FibroTouch Examination<br>* Liver stiffness measurements are performed using FibroTouch and the procedure is non-invasive and painless.<br>Device: FibroScan Examination<br>* Liver stiffness measurements are performed using another transient elastography, FibroScan, and the procedure is non-invasive and painless.<br>Device: Ultrasonic B Examination<br>* The ultrasonic B examination is made at an empty stomach for ≥8h. The inner diameter of liver, spleen, gallbladder, portal vein and splenoportal vein is measured through the ordinary two-dimensional ultrasonic examination. The echo data of liver surface/edge/parenchyma and gallbladder wall is scored to evaluate the severity of fibrosis.<br>|
| S2<br>S2 = portal fibrosis with few septa | Device: FibroTouch Examination<br>* Liver stiffness measurements are performed using FibroTouch and the procedure is non-invasive and painless.<br>Device: FibroScan Examination<br>* Liver stiffness measurements are performed using another transient elastography, FibroScan, and the procedure is non-invasive and painless.<br>Device: Ultrasonic B Examination<br>* The ultrasonic B examination is made at an empty stomach for ≥8h. The inner diameter of liver, spleen, gallbladder, portal vein and splenoportal vein is measured through the ordinary two-dimensional ultrasonic examination. The echo data of liver surface/edge/parenchyma and gallbladder wall is scored to evaluate the severity of fibrosis.<br>|
| S3<br>S3 = numerous septa without cirrhosis | Device: FibroTouch Examination<br>* Liver stiffness measurements are performed using FibroTouch and the procedure is non-invasive and painless.<br>Device: FibroScan Examination<br>* Liver stiffness measurements are performed using another transient elastography, FibroScan, and the procedure is non-invasive and painless.<br>Device: Ultrasonic B Examination<br>* The ultrasonic B examination is made at an empty stomach for ≥8h. The inner diameter of liver, spleen, gallbladder, portal vein and splenoportal vein is measured through the ordinary two-dimensional ultrasonic examination. The echo data of liver surface/edge/parenchyma and gallbladder wall is scored to evaluate the severity of fibrosis.<br>|
| S4<br>S4 = liver cirrhosis (compensatory stage) | Device: FibroTouch Examination<br>* Liver stiffness measurements are performed using FibroTouch and the procedure is non-invasive and painless.<br>Device: FibroScan Examination<br>* Liver stiffness measurements are performed using another transient elastography, FibroScan, and the procedure is non-invasive and painless.<br>Device: Ultrasonic B Examination<br>* The ultrasonic B examination is made at an empty stomach for ≥8h. The inner diameter of liver, spleen, gallbladder, portal vein and splenoportal vein is measured through the ordinary two-dimensional ultrasonic examination. The echo data of liver surface/edge/parenchyma and gallbladder wall is scored to evaluate the severity of fibrosis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The coincidence for diagnosis of liver fibrosis and cirrhosis between liver stiffness measurement (LSM) of FibroTouch and liver biopsy by ROC analysis | Performance of liver stiffness measurement (LSM, kPa) of FibroTouch for the non-invasive and quantitative diagnosis of liver fibrosis and cirrhosis in CHB patients with stage S0 (no fibrosis), S1 (portal fibrosis without septa), S2 (portal fibrosis with few septa), S3 (numerous septa without cirrhosis) and S4 (compensatory stage of cirrhosis) will be assessed using ROC analysis, liver biopsy as the reference. | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The coincidence for diagnosis of liver fibrosis and cirrhosis between liver stiffness measurement (LSM) of FibroTouch and FibroScan by ROC analysis | Performance of liver stiffness measurement (LSM, kPa) of FibroTouch and FibroScan for the non-invasive and quantitative diagnosis of liver fibrosis and cirrhosis in CHB patients will be compared using ROC analysis. | Participants will be offered a FibroScan examination at the same time of FibroTouch examination. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CHB