Chronic Hepatitis B, Cirrhosis, Liver Fibrosis
Conditions
Keywords
CHB
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.
Interventions
DEVICEFibroTouch Examination
Liver stiffness measurements are performed using FibroTouch and the procedure is non-invasive and painless.
DEVICEFibroScan Examination
Liver stiffness measurements are performed using another transient elastography, FibroScan, and the procedure is non-invasive and painless.
DEVICEUltrasonic B Examination
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.
Sponsors
Beijing Friendship Hospital
The Military General Hospital of Beijing, PLA
The First Affiliated Hospital, Third Military University
The First Affiliated Hospital of the Fourth Military Medical University
The First Hospital of Jilin University
Hebei Medical University Third Hospital
Henan Provincial People's Hospital
Jiangsu Provincial People's Hospital
Ruijin Hospital
West China Hospital
Tianjin Third Central Hospital
No.85 Hospital, Changning, Shanghai, China
Third Affiliated Hospital, Sun Yat-Sen University
Hospital of Chinese Medicine of the Xinjiang Uygur Autonomous Region
The China-Japan Friendship Hospital
Peking University Clinical Research Institute (PUCRI)
Wuxi Hisky Medical Technology Co Ltd
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. | Altogether 412 patients were included to analyze the diagnostic performance of FibroTouch. The area under the receiver operating characteristic curve for the LSM was 0.846 (95% confidence interval CI 0.808-0.880) for fibrosis stage ≥ F1, 0.850 for ≥ F2, 0.908 for ≥ F3 and 0.874 for F4. Optimal LSM cut-off values for diagnosing fibrosis stage ≥ F1, ≥ F2, ≥ F3, and F4 were 5.5 kPa, 7.85 kPa, 10.0 kPa, and 12.7 kPa, respectively. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients With Chronic Hepatitis B The METAVIR scoring system classifies liver fibrosis in five stages as follows: F0=no fibrosis F1 = portal fibrosis without septa F2 = portal fibrosis with few septa F3 = numerous septa without cirrhosis F4 = liver cirrhosis (compensatory stage)
Clinical and laboratory investigations; Non-invasive serum markers of liver fibrosis; Non-invasive serum markers of liver fibrosis; Assessment of liver pathology | 412 |
| Total | 412 |
Baseline characteristics
| Characteristic | Patients With Chronic Hepatitis B |
|---|---|
| Age, Continuous | 39.4 years STANDARD_DEVIATION 10.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 412 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Sex: Female, Male Female | 276 Participants |
| Sex: Female, Male Male | 136 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 162 | 0 / 118 | 0 / 95 | 0 / 26 |
| other Total, other adverse events | 0 / 11 | 0 / 162 | 0 / 118 | 0 / 95 | 0 / 26 |
| serious Total, serious adverse events | 0 / 11 | 0 / 162 | 0 / 118 | 0 / 95 | 0 / 26 |
Outcome results
Primary
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
Altogether 412 patients were included to analyze the diagnostic performance of FibroTouch. The area under the receiver operating characteristic curve for the LSM was 0.846 (95% confidence interval CI 0.808-0.880) for fibrosis stage ≥ F1, 0.850 for ≥ F2, 0.908 for ≥ F3 and 0.874 for F4. Optimal LSM cut-off values for diagnosing fibrosis stage ≥ F1, ≥ F2, ≥ F3, and F4 were 5.5 kPa, 7.85 kPa, 10.0 kPa, and 12.7 kPa, respectively.
Time frame: 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.
Population: ROC analysis is based on a binary classification model, which refers to models with only two types of output results, such as: (positive/negative) (diseased/not diseased).Due to the particularity of this analysis method, there is no ROC value for F0.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| F1 Fibrosis Stage | 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 | 0.846 probability |
| F2 Fibrosis Stage | 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 | 0.850 probability |
| F3 Fibrosis Stage | 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 | 0.908 probability |
| F4 Fibrosis Stage | 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 | 0.874 probability |