Ignite Creation Date:
2024-05-06 @ 7:41 PM
Last Modification Date:
2024-10-26 @ 3:11 PM
Study NCT ID:
NCT06097338
Status:
NOT_YET_RECRUITING
Last Update Posted:
2023-10-24
First Post:
2023-10-18
Brief Title:
Quantitative US for Evaluation of Hepatic Steatosis in MAFLD With UDFF
Sponsor:
Qianfoshan Hospital
Organization:
Qianfoshan Hospital
Study Overview
Official Title:
Quantitative US for Evaluation of Hepatic Steatosis in MAFLD With UDFF
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Ultrasound Derived Fat Fraction UDFF Evaluation of Metabolic Related Fatty Liver Disease MAFLD in obesity Patients Metabolic fatty liver disease MAFLD formerly known as Nonalcoholic Fatty Liver Disease NAFLD is the most common chronic liver disease in the world at present with a incidence rate of about 30 In the United States NAFLD is the third leading cause of hepatocellular carcinoma and early assessment and diagnosis of liver steatosis characteristics are crucial for timely treatment or intervention to reduce the risk of liver fibrosis and inhibit disease progression Liver biopsy is considered as the gold standard for evaluating grading and determining inflammatory activity of liver steatosis and fibrosis However liver biopsy are invasive and pathological evaluation differences among observers which makes it difficult to widely use and repeat especially for dynamic evaluation of patients during the treatment process
Ultrasound Derviced Fat Fraction UDFF is a unique technology for non-invasive quantification of liver fat content which is equipped on the Siemens ACUSON Sequoia ultrasound system UDFF is calculated from two parameter values attenuation coefficient AC and backscatter coefficient BSC SWE shear wave elastography is becoming widely used and is recommended for the evaluation of liver fibrosis by some guidelines in patients with chronic liver diseases such as viral hepatitis These two technologies UDFFSWE can be achieved on the same probe and this detection technology is non-invasive painless simple and reliable
Bariatric surgery BS also known as metabolic weight loss surgery is currently recognized as the most significant and long-lasting method for treating obesity It can significantly improve obesity related comorbidities as well as long-term improvement in postoperative quality of life and mental state
This study will aim on analysis of the liver ultrasound characteristics of patients who plan to undergo bariatric surgery By using UDFF and elastic shear wave technology UDFFSWE a new non-invasive ultrasound evaluation method for MAFLD grading diagnosis of simple fatty liver fatty hepatitis liver fibrosis and related cirrhosis will be proposed and the incidence and risk factors of MAFLD in overweight and obese patients will be explored The reversal effect of weight loss therapy on MAFLD in obese patients
Ultrasound Derviced Fat Fraction UDFF is a unique technology for non-invasive quantification of liver fat content which is equipped on the Siemens ACUSON Sequoia ultrasound system UDFF is calculated from two parameter values attenuation coefficient AC and backscatter coefficient BSC SWE shear wave elastography is becoming widely used and is recommended for the evaluation of liver fibrosis by some guidelines in patients with chronic liver diseases such as viral hepatitis These two technologies UDFFSWE can be achieved on the same probe and this detection technology is non-invasive painless simple and reliable
Bariatric surgery BS also known as metabolic weight loss surgery is currently recognized as the most significant and long-lasting method for treating obesity It can significantly improve obesity related comorbidities as well as long-term improvement in postoperative quality of life and mental state
This study will aim on analysis of the liver ultrasound characteristics of patients who plan to undergo bariatric surgery By using UDFF and elastic shear wave technology UDFFSWE a new non-invasive ultrasound evaluation method for MAFLD grading diagnosis of simple fatty liver fatty hepatitis liver fibrosis and related cirrhosis will be proposed and the incidence and risk factors of MAFLD in overweight and obese patients will be explored The reversal effect of weight loss therapy on MAFLD in obese patients
Detailed Description:
1 Research background
MAFLD NAFLD is considered to be the most common adult chronic liver disease in the world affecting more than 30 of the worlds population Previous studies have shown that 55-80 of NAFLD patients have type 2 diabetes Early assessment and diagnosis of liver steatosis characteristics is crucial for timely treatment or intervention to reduce the risk of liver fibrosis and inhibit disease progression in MAFLDNAFLD
At present liver biopsy is considered as the gold standard for evaluating grading and determining inflammatory activity of liver steatosis and fibrosis However liver biopsy has certain limitations such as pain bleeding infection bile leakage leading to the inability to widely use and repeat detection of liver biopsy especially for dynamic evaluation of patients during treatment
Therefore in recent years non-invasive diagnosis of liver fat content has attracted much attention Conventional ultrasound is the most commonly used imaging method for evaluating liver steatosis Conventional abdominal CT can also be used to diagnose fatty liver but its sensitivity is similar to or even lower than ultrasound accompanied by radiation which limits its application in screening and evaluation of fatty liver Other imaging methods include magnetic resonance spectroscopy MRS and magnetic resonance chemical shift coding MRI Magnetic resonance spectroscopy MRS uses the difference in resonance frequency between water and fat proton signals to measure proton density fat fraction PDFF MRI-PDFF is closely related to histological evaluation of liver fat content and is currently the most sensitive non-invasive method for detecting and quantifying liver steatosis
UDFF is a novel and unique technology for non-invasive quantification of liver fat content equipped on the Siemens ACUSON Sequoia ultrasound system UDFF is calculated from two parameter values Attenuation Coefficients AC and Backscatter Coefficients BSC These two parameters are determined by comparing the frequency content of backscattered echo signals at different depths within the tissue and the reference module of the simulated tissue The AC and BSC values of the reference module are known to be fixed By comparing the attenuation of tissues can be separated and their AC can be estimated The ratio of two spectra and the AC of the module can also be used to estimate the backscatter coefficient of tissue samples After calculating and estimating the BSC a unique proprietary mathematical algorithm was used to estimate the UDFF value of the tissue sample at 3MHz Convert BSC to UDFF in percentage using a special algorithm P linearize the 3MHz BSC to obtain UDFF Unlike AC and BSC values the UDFF obtained through special algorithms has a linear relationship with liver fat content As the fat content level increases the UDFF index value also increases
UDFF can quickly and non-invasive quantify liver fat content within seconds during routine abdominal ultrasound examination This technology is non-invasive painless simple and reliable and will contribute to the diagnosis and dynamic evaluation of MAFLD during the treatment process playing an important role in the patients prognosis
In addition to fat deposition in the liver balloon like transformation of liver cells liver fibrosis is an important monitoring indicator for the progression of MAFLD On the Siemens Sequoia ultrasound system the measurement of shear wave elastography SWE can be achieved on the same probe as UDFF technology simultaneously
As MAFLD is a series of diseases and may be combined with a variety of metabolic related complications such as cardiovascular disease type 2 diabetes leading to the complexity of MAFLD treatment The initial treatment plan for MAFLD currently involves lifestyle changes including controlling diet and exercise ultimately achieving weight loss Weight loss regardless of the method used is strongly correlated with histological improvement in MAFLD with even a 5 weight loss indicating a reduction in patients fatty liver
Bariatric surgery BS is a very attractive choice for severely obese patients After bariatric surgery long-term weight loss 15-25 and diabetes remission can occur as well as mortality cardiovascular events and tumor occurrence Studies have shown that bariatric surgery can significantly reduce the liver NAFLD activity score from 5 to 1 and 338 of patients have reduced liver fibrosis Due to the use of liver biopsy to evaluate liver histological changes in NAFLDMAFLD observation during bariatric surgery liver biopsy cannot be widely used and repeatedly detected due to its invasive nature and differences in pathological evaluation among observers Especially for patients during treatment and follow-up flexible dynamic evaluation is difficult to achieve
This study will conduct a detailed analysis of the liver ultrasound characteristics of patients who plan to undergo bariatric surgery By using UDFFSWE technology a new method for non-invasive evaluation of MAFLD grading diagnosis of simple fatty liver fatty hepatitis fatty liver fibrosis and related cirrhosis will be proposed The incidence and risk factors of overweight and obese patients with MAFLD will be explored and the reversal effect of weight loss treatment on MAFLD in obese patients will be explored
2 Research aims
The aim of this study is to prospectively evaluate UDFF for detection of hepatic steatosis and quantification of liver fat content meanwhile to assess SWE for detection of liver fibrosis using a DAX probe in patients who plan to undergo bariatric surgery Through UDFF technology and elastic shear wave technology a new non-invasive ultrasound evaluation method for MAFLD grading diagnosis of simple fatty liver fatty hepatitis fatty liver fibrosis and related cirrhosis will be proposed
3 Research protocol
UDFF technology was used to detect liver fat fraction in patients who plan to undergo bariatric surgery while SWE was used to monitor liver stiffness Pathological diagnosis was used as the gold standard to determine the correlation between relevant feature quantities and fibrosis inflammation grading and steatosis grading Multiple regression equations were established to form UDFF scores for different degrees of MAFLD and different grading diagnostic thresholds Analyze its diagnostic effectiveness through internal and external verification methods
Each participant will undergo ultrasound examination UDFF SWE before bariatric surgery and 1 month 3 months 6 months and 12months after surgery
31 Observe items
311 General clinical information collection
Gender age height weight waist BMI blood pressure history of hepatitis history of diabetes antiviral treatment
Alcohol drinking history calculation formula daily alcohol intake gramsalcohol consumption milliliters Alcohol content Specific gravity of alcohol 08
312 Serum biochemical parameters 3121 Blood testing RBC red blood cells HGB hemoglobin WBC white blood cells NEUT neutrophil percentage PLT platelet count 3122 Serum TB total bilirubin DB direct bilirubin IB indirect bilirubin ALB albumin AST aspartate aminotransferase ALT alanine aminotransferase GGT γ- Glutamyl transpeptidase ALP alkaline phosphatase SCr blood creatinine UA blood uric acid TG triglycerides CHOL total cholesterol HDL-C high-density lipoprotein cholesterol LDL-C low-density lipoprotein cholesterol glucoseinsulin GHb glycated hemoglobin 3123 Blood coagulation test PT prothrombin time INR international standardized ratio Interleukin 68 CRP C-reactive protein 3124 Serum HBsAgHBsAbHBeAgHBeAbHBcAbHBV DNA 313 Conventional ultrasound and UDFFSWE examination 3131 Equipment Siemens ACUSON Sequoia ultrasound system with C5-1 probe and DAX probe
3132 Preparation before examination patients fast for at least 4 hours and after resting for at least 20 minutes Avoid testing after diet especially caffeine and smoking
3133 UDFF observer training It should be performed by an experienced sonographer Provide more than 50 training sessions for beginners
3134 Instrument settings Unified settings for frequency gain etc The total depth of the image during UDFF measurement is within 15cm
3135 Conventional ultrasound examination C5-1 probe abdominal wall thickness parenchymal echo of the liver and spleen size of spleen size of liver lobes Smooth degree of liver capsule Portal vein diameter and blood flow velocity
3136 UDFFSWE examination DAX probe The participant lay in a supine position with the probe placed between the right ribs or under the xiphoid process avoiding the intrahepatic duct structure The sampling boxes are placed in the right lobe of the liver S5 best followed by S8 and the left lobe of the liver S2 or S3 segment respectively Instruct the participant to calm down and hold their breath before measuring to avoid Valsalva movements Measure the left and right lobes of the liver 5 times store the map and record the measured values
3137 Images Storages 31371 Liver grayscale images left lobes longitudinal and transverse sections under the xiphoid process including the smoothness of the liver capsule right lobe oblique diameter under the right rib showing the second hepatic hilum right intercostal section and liver kidney contrast section 31372 Portal vein diameter color Doppler ultrasound and flow velocity measurement maps
31373 Measurement and storage of abdominal wall thickness 31374 Measurement of spleen length and thickness 31375 UDFFSWE 5 measurement pictures for each left and right lobes
314 Pathological examination before surgery Using 18g or 20g puncture needles for ultrasound-guided percutaneous liver biopsy the length of the tissue specimen should be 15mm and include at least 6 complete portal areas All liver biopsy specimens were independently evaluated by senior pathologists who were unaware of clinical data The liver Steatosis Activity and Fibrosis SAF scoring system will be used as pathological diagnosis standard for MAFLD diagnosis
32 Statistical Analysis Plan
321 Descriptive statistics on demographic data will be presented as total number and percentage Continuous and normally distributed data will be analyzed with ANOVA and reported as mean and SD Continuous and not normally distributed data will be analyzed using the Kruskal-Wallis test and reported as median and interquartile ranges IQR For categoric data variables will be described as number and percentage and the Fisher exact test is used for analysis
322 The cut-off value for the diagnosis of hepatic steatosis was 5 both for UDFF as determined by previous studies Agreement and correlation between UDFF and pathological liver steatosis will be evaluated by the Bland-Altman dierence plot one-sample T test and Pearsons correlation test The diagnostic value of B-mode US and UDFF measurements for the detection of steatosis will be assessed by the calculation of sensitivity specificity positive and negative predictive values PPV and NPV and accuracy Receiver operating characteristic curves ROCs will be constructed for B-mode US and UDFF by taking pathological liver steatosis the standard of reference and area under the curves AUC-ROC will be calculated comparison of ROC curves will be performed with the method described by Delong et al p values 005 will be considered statistically significant Statistical analysis will be performed using commercially available software SPSS 23 IBM and MedCalc 179 MedCalc Software
MAFLD NAFLD is considered to be the most common adult chronic liver disease in the world affecting more than 30 of the worlds population Previous studies have shown that 55-80 of NAFLD patients have type 2 diabetes Early assessment and diagnosis of liver steatosis characteristics is crucial for timely treatment or intervention to reduce the risk of liver fibrosis and inhibit disease progression in MAFLDNAFLD
At present liver biopsy is considered as the gold standard for evaluating grading and determining inflammatory activity of liver steatosis and fibrosis However liver biopsy has certain limitations such as pain bleeding infection bile leakage leading to the inability to widely use and repeat detection of liver biopsy especially for dynamic evaluation of patients during treatment
Therefore in recent years non-invasive diagnosis of liver fat content has attracted much attention Conventional ultrasound is the most commonly used imaging method for evaluating liver steatosis Conventional abdominal CT can also be used to diagnose fatty liver but its sensitivity is similar to or even lower than ultrasound accompanied by radiation which limits its application in screening and evaluation of fatty liver Other imaging methods include magnetic resonance spectroscopy MRS and magnetic resonance chemical shift coding MRI Magnetic resonance spectroscopy MRS uses the difference in resonance frequency between water and fat proton signals to measure proton density fat fraction PDFF MRI-PDFF is closely related to histological evaluation of liver fat content and is currently the most sensitive non-invasive method for detecting and quantifying liver steatosis
UDFF is a novel and unique technology for non-invasive quantification of liver fat content equipped on the Siemens ACUSON Sequoia ultrasound system UDFF is calculated from two parameter values Attenuation Coefficients AC and Backscatter Coefficients BSC These two parameters are determined by comparing the frequency content of backscattered echo signals at different depths within the tissue and the reference module of the simulated tissue The AC and BSC values of the reference module are known to be fixed By comparing the attenuation of tissues can be separated and their AC can be estimated The ratio of two spectra and the AC of the module can also be used to estimate the backscatter coefficient of tissue samples After calculating and estimating the BSC a unique proprietary mathematical algorithm was used to estimate the UDFF value of the tissue sample at 3MHz Convert BSC to UDFF in percentage using a special algorithm P linearize the 3MHz BSC to obtain UDFF Unlike AC and BSC values the UDFF obtained through special algorithms has a linear relationship with liver fat content As the fat content level increases the UDFF index value also increases
UDFF can quickly and non-invasive quantify liver fat content within seconds during routine abdominal ultrasound examination This technology is non-invasive painless simple and reliable and will contribute to the diagnosis and dynamic evaluation of MAFLD during the treatment process playing an important role in the patients prognosis
In addition to fat deposition in the liver balloon like transformation of liver cells liver fibrosis is an important monitoring indicator for the progression of MAFLD On the Siemens Sequoia ultrasound system the measurement of shear wave elastography SWE can be achieved on the same probe as UDFF technology simultaneously
As MAFLD is a series of diseases and may be combined with a variety of metabolic related complications such as cardiovascular disease type 2 diabetes leading to the complexity of MAFLD treatment The initial treatment plan for MAFLD currently involves lifestyle changes including controlling diet and exercise ultimately achieving weight loss Weight loss regardless of the method used is strongly correlated with histological improvement in MAFLD with even a 5 weight loss indicating a reduction in patients fatty liver
Bariatric surgery BS is a very attractive choice for severely obese patients After bariatric surgery long-term weight loss 15-25 and diabetes remission can occur as well as mortality cardiovascular events and tumor occurrence Studies have shown that bariatric surgery can significantly reduce the liver NAFLD activity score from 5 to 1 and 338 of patients have reduced liver fibrosis Due to the use of liver biopsy to evaluate liver histological changes in NAFLDMAFLD observation during bariatric surgery liver biopsy cannot be widely used and repeatedly detected due to its invasive nature and differences in pathological evaluation among observers Especially for patients during treatment and follow-up flexible dynamic evaluation is difficult to achieve
This study will conduct a detailed analysis of the liver ultrasound characteristics of patients who plan to undergo bariatric surgery By using UDFFSWE technology a new method for non-invasive evaluation of MAFLD grading diagnosis of simple fatty liver fatty hepatitis fatty liver fibrosis and related cirrhosis will be proposed The incidence and risk factors of overweight and obese patients with MAFLD will be explored and the reversal effect of weight loss treatment on MAFLD in obese patients will be explored
2 Research aims
The aim of this study is to prospectively evaluate UDFF for detection of hepatic steatosis and quantification of liver fat content meanwhile to assess SWE for detection of liver fibrosis using a DAX probe in patients who plan to undergo bariatric surgery Through UDFF technology and elastic shear wave technology a new non-invasive ultrasound evaluation method for MAFLD grading diagnosis of simple fatty liver fatty hepatitis fatty liver fibrosis and related cirrhosis will be proposed
3 Research protocol
UDFF technology was used to detect liver fat fraction in patients who plan to undergo bariatric surgery while SWE was used to monitor liver stiffness Pathological diagnosis was used as the gold standard to determine the correlation between relevant feature quantities and fibrosis inflammation grading and steatosis grading Multiple regression equations were established to form UDFF scores for different degrees of MAFLD and different grading diagnostic thresholds Analyze its diagnostic effectiveness through internal and external verification methods
Each participant will undergo ultrasound examination UDFF SWE before bariatric surgery and 1 month 3 months 6 months and 12months after surgery
31 Observe items
311 General clinical information collection
Gender age height weight waist BMI blood pressure history of hepatitis history of diabetes antiviral treatment
Alcohol drinking history calculation formula daily alcohol intake gramsalcohol consumption milliliters Alcohol content Specific gravity of alcohol 08
312 Serum biochemical parameters 3121 Blood testing RBC red blood cells HGB hemoglobin WBC white blood cells NEUT neutrophil percentage PLT platelet count 3122 Serum TB total bilirubin DB direct bilirubin IB indirect bilirubin ALB albumin AST aspartate aminotransferase ALT alanine aminotransferase GGT γ- Glutamyl transpeptidase ALP alkaline phosphatase SCr blood creatinine UA blood uric acid TG triglycerides CHOL total cholesterol HDL-C high-density lipoprotein cholesterol LDL-C low-density lipoprotein cholesterol glucoseinsulin GHb glycated hemoglobin 3123 Blood coagulation test PT prothrombin time INR international standardized ratio Interleukin 68 CRP C-reactive protein 3124 Serum HBsAgHBsAbHBeAgHBeAbHBcAbHBV DNA 313 Conventional ultrasound and UDFFSWE examination 3131 Equipment Siemens ACUSON Sequoia ultrasound system with C5-1 probe and DAX probe
3132 Preparation before examination patients fast for at least 4 hours and after resting for at least 20 minutes Avoid testing after diet especially caffeine and smoking
3133 UDFF observer training It should be performed by an experienced sonographer Provide more than 50 training sessions for beginners
3134 Instrument settings Unified settings for frequency gain etc The total depth of the image during UDFF measurement is within 15cm
3135 Conventional ultrasound examination C5-1 probe abdominal wall thickness parenchymal echo of the liver and spleen size of spleen size of liver lobes Smooth degree of liver capsule Portal vein diameter and blood flow velocity
3136 UDFFSWE examination DAX probe The participant lay in a supine position with the probe placed between the right ribs or under the xiphoid process avoiding the intrahepatic duct structure The sampling boxes are placed in the right lobe of the liver S5 best followed by S8 and the left lobe of the liver S2 or S3 segment respectively Instruct the participant to calm down and hold their breath before measuring to avoid Valsalva movements Measure the left and right lobes of the liver 5 times store the map and record the measured values
3137 Images Storages 31371 Liver grayscale images left lobes longitudinal and transverse sections under the xiphoid process including the smoothness of the liver capsule right lobe oblique diameter under the right rib showing the second hepatic hilum right intercostal section and liver kidney contrast section 31372 Portal vein diameter color Doppler ultrasound and flow velocity measurement maps
31373 Measurement and storage of abdominal wall thickness 31374 Measurement of spleen length and thickness 31375 UDFFSWE 5 measurement pictures for each left and right lobes
314 Pathological examination before surgery Using 18g or 20g puncture needles for ultrasound-guided percutaneous liver biopsy the length of the tissue specimen should be 15mm and include at least 6 complete portal areas All liver biopsy specimens were independently evaluated by senior pathologists who were unaware of clinical data The liver Steatosis Activity and Fibrosis SAF scoring system will be used as pathological diagnosis standard for MAFLD diagnosis
32 Statistical Analysis Plan
321 Descriptive statistics on demographic data will be presented as total number and percentage Continuous and normally distributed data will be analyzed with ANOVA and reported as mean and SD Continuous and not normally distributed data will be analyzed using the Kruskal-Wallis test and reported as median and interquartile ranges IQR For categoric data variables will be described as number and percentage and the Fisher exact test is used for analysis
322 The cut-off value for the diagnosis of hepatic steatosis was 5 both for UDFF as determined by previous studies Agreement and correlation between UDFF and pathological liver steatosis will be evaluated by the Bland-Altman dierence plot one-sample T test and Pearsons correlation test The diagnostic value of B-mode US and UDFF measurements for the detection of steatosis will be assessed by the calculation of sensitivity specificity positive and negative predictive values PPV and NPV and accuracy Receiver operating characteristic curves ROCs will be constructed for B-mode US and UDFF by taking pathological liver steatosis the standard of reference and area under the curves AUC-ROC will be calculated comparison of ROC curves will be performed with the method described by Delong et al p values 005 will be considered statistically significant Statistical analysis will be performed using commercially available software SPSS 23 IBM and MedCalc 179 MedCalc Software
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None