Ignite Creation Date:
2024-05-06 @ 4:03 PM
Last Modification Date:
2024-10-26 @ 2:02 PM
Study NCT ID:
NCT04850547
Status:
UNKNOWN
Last Update Posted:
2021-04-20
First Post:
2021-04-18
Brief Title:
Effect of Fatty Liver Disease on Bone Density
Sponsor:
Sohag University
Organization:
Sohag University
Study Overview
Official Title:
Vitamin D Status and Bone Turnover Markers in Patients With Non Alcoholic Fatty Liver Disease
Status:
UNKNOWN
Status Verified Date:
2021-04
Last Known Status:
NOT_YET_RECRUITING
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:
Non Alcohlic Fatty Liver NAFLD is a spectrum of diseases that ranges from accumulation of fat in the liver Hepatosteatosis that may be accompanied by inflammation Steatohepatitis to necrosis fibrosis and even cirrhosis resembling alcoholic hepatitis in the absence of alcoholic abuse Pardee et al 2012
It has been estimated that the global prevalence of NAFLD is as high as one billion In the United States NAFLD is estimated to be the most common cause of chronic liver disease affecting between 80 and 100 million individuals among whom nearly 25 progress to NASH Loomba et al 2013
In general the prevalence of NAFLD has increased over the last 20 years The Middle East and South America have the highest NAFLD prevalence at 31 and 32 respectively with the lowest prevalence in Africa at 135 Younossi et al 2016
Liver biopsy LB is still the standard test of NAFLD diagnosis and the presence of early liver fibrosis However histologic lesions are not evenly distributed throughout the liver A sampling error is the biggest limitation in the diagnosis of NAFLD by LB with inflammatory lesions and ballooning degeneration potentially resulting in misdiagnoses and staging inaccuracies Lee et al 2016
To overcome these limitations several non-invasive markers have been used instead of liver biopsy These methods are either laboratory markers or imaging modalities Controlled attenuation parameter CAP is a new technology based on the principle of the ultrasonic attenuation of transient elastography depending on the viscosity fat of the medium liver and the distance of propagation of the ultrasonic signals into the liver providing a useful method for the quantitative detection of liver fat content and is considered a better assessment method for hepatic steatosis Compared with ultrasound this technology improves the sensitivity and specificity for the diagnosis of fatty liver and can be used for universal screening diagnosis and follow-up in NAFLD patients Sasso et al 2016
NAFLD is known to be closely associated with metabolic conditions including insulin resistance abdominal obesity dyslipidaemia and type 2 diabetes and is thus regarded as the hepatic manifestation of the metabolic syndrome Ballestri 2016 In recent epidemiological studies NAFLD was shown to be connected with diseases that are usually not dependent on obesity such as sarcopenia and osteoporosis Poggiogalle et al 2017
Osteoporosis is becoming a public health problem all over the world Disability resulting from low-energy fractures eg hip or vertebral fractures is the major concern for early detection and treatment It is estimated that osteoporosis affects 200 million women worldwide Kanis et al 2007
Liver is the source of many proteins and is the regulator of several pathways involving bone metabolism one of the most well-known of all is vitamin D metabolism pathway Considering the role of liver in bone metabolism the association between NAFLD and bone abnormalities is not surprising especially with substantial supporting evidences in recent years Eshraghian et al 2017
Besides its role in the calcium and bone metabolism vitamin D may also exert pleiotropic effects in many tissues NAFLD patients were reported to have a marked reduction in serum 25OH vitamin D when compared with controls Yilmaz et al 2011
In adults bone is constantly being remodeled first being broken down bone resorption and then being rebuilt bone formation The resorption and reformation of bone is important for repair of microfractures and to allow modification of structure in response to stress and other biomechanical forces Bone formation is normally tightly coupled to bone resorption so that bone mass does not change Bone diseases occur when formation and resorption are uncoupled Several assays are available that measure bone turnover markers BTMs These assays measure collagen breakdown products and other molecules released from osteoclasts and osteoblasts during the process of bone resorption and formation Markers that are specific to bone formation include bone-specific alkaline phosphatase BSAP osteocalcin and N-terminal propeptide of type I procollagen PINP markers specific to bone resorption include N-terminal telopeptide of type I collagen NTX C-terminal telopeptide of type I collagen CTX and pyridinoline cross-links Rosen et al 2019
It has been estimated that the global prevalence of NAFLD is as high as one billion In the United States NAFLD is estimated to be the most common cause of chronic liver disease affecting between 80 and 100 million individuals among whom nearly 25 progress to NASH Loomba et al 2013
In general the prevalence of NAFLD has increased over the last 20 years The Middle East and South America have the highest NAFLD prevalence at 31 and 32 respectively with the lowest prevalence in Africa at 135 Younossi et al 2016
Liver biopsy LB is still the standard test of NAFLD diagnosis and the presence of early liver fibrosis However histologic lesions are not evenly distributed throughout the liver A sampling error is the biggest limitation in the diagnosis of NAFLD by LB with inflammatory lesions and ballooning degeneration potentially resulting in misdiagnoses and staging inaccuracies Lee et al 2016
To overcome these limitations several non-invasive markers have been used instead of liver biopsy These methods are either laboratory markers or imaging modalities Controlled attenuation parameter CAP is a new technology based on the principle of the ultrasonic attenuation of transient elastography depending on the viscosity fat of the medium liver and the distance of propagation of the ultrasonic signals into the liver providing a useful method for the quantitative detection of liver fat content and is considered a better assessment method for hepatic steatosis Compared with ultrasound this technology improves the sensitivity and specificity for the diagnosis of fatty liver and can be used for universal screening diagnosis and follow-up in NAFLD patients Sasso et al 2016
NAFLD is known to be closely associated with metabolic conditions including insulin resistance abdominal obesity dyslipidaemia and type 2 diabetes and is thus regarded as the hepatic manifestation of the metabolic syndrome Ballestri 2016 In recent epidemiological studies NAFLD was shown to be connected with diseases that are usually not dependent on obesity such as sarcopenia and osteoporosis Poggiogalle et al 2017
Osteoporosis is becoming a public health problem all over the world Disability resulting from low-energy fractures eg hip or vertebral fractures is the major concern for early detection and treatment It is estimated that osteoporosis affects 200 million women worldwide Kanis et al 2007
Liver is the source of many proteins and is the regulator of several pathways involving bone metabolism one of the most well-known of all is vitamin D metabolism pathway Considering the role of liver in bone metabolism the association between NAFLD and bone abnormalities is not surprising especially with substantial supporting evidences in recent years Eshraghian et al 2017
Besides its role in the calcium and bone metabolism vitamin D may also exert pleiotropic effects in many tissues NAFLD patients were reported to have a marked reduction in serum 25OH vitamin D when compared with controls Yilmaz et al 2011
In adults bone is constantly being remodeled first being broken down bone resorption and then being rebuilt bone formation The resorption and reformation of bone is important for repair of microfractures and to allow modification of structure in response to stress and other biomechanical forces Bone formation is normally tightly coupled to bone resorption so that bone mass does not change Bone diseases occur when formation and resorption are uncoupled Several assays are available that measure bone turnover markers BTMs These assays measure collagen breakdown products and other molecules released from osteoclasts and osteoblasts during the process of bone resorption and formation Markers that are specific to bone formation include bone-specific alkaline phosphatase BSAP osteocalcin and N-terminal propeptide of type I procollagen PINP markers specific to bone resorption include N-terminal telopeptide of type I collagen NTX C-terminal telopeptide of type I collagen CTX and pyridinoline cross-links Rosen et al 2019
Detailed Description:
All included patients will be subjected to the following
1 Complete history taking including age sex current medical history eg hypertension diabetes mellitus cardiovascular disease renal thyroid parathyroid diseases and menopausal status daily alcohol consumption and smoking status will be recorded from interviews with the participants during the examination
2 thorough clinical examination The participants anthropometric measurements will be obtained including their body weight height waist circumference WC and body mass index BMI
General examination Arterial blood pressure will be recorded and for detection of stigmata of chronic liver disease
Abdominal examination will be done for assessment of the size of the liver and spleen
3 Diagnosis of NAFLD
The diagnosis will be based on abdominal ultrasound findings and will be confirmed by fibroscan examination as the following
1 Abdominal ultrasound steatosis will be graded according to Quinn and Gosink 1985 as the following
Grade I Minimal diffuse increase in the fine echoes Liver appears bright compared to the cortex of the kidney
Grade II Moderate diffuse increase in the fine echoes Slightly impaired visualization of the intrahepatic vessels and diaphragm
Grade III Marked increase in the fine echoes Poor or no visualization of intrahepatic vessels and diaphragm and poor penetration of the posterior segment of the right lobe of the liver
2 Fibosscan to evaluate steatosis grades by CAP score and fibrosis stages as described by Sasso et al 2010
4 Laboratory investigations
1 Complete Blood Count CBC
2 Liver profile alanine aminotransferase ALT aspartate aminotransferase AST serum albumin total and direct bilirubin prothrombin time and INR
3 Renal profile creatinine and urine analysis
4 Total cholesterol triglyceride TG high-density lipoprotein cholesterol HDL-C low-density lipoprotein cholesterol LDL-C
5 Fasting blood sugar
6 HBsAg HCV Ab Viral markers
7 25-hydroxyl-vitamin D 25OHD in serum
8 Serum Osteocalcin as a marker of bone formation and serum NTX as a marker of bone resorption
1 Complete history taking including age sex current medical history eg hypertension diabetes mellitus cardiovascular disease renal thyroid parathyroid diseases and menopausal status daily alcohol consumption and smoking status will be recorded from interviews with the participants during the examination
2 thorough clinical examination The participants anthropometric measurements will be obtained including their body weight height waist circumference WC and body mass index BMI
General examination Arterial blood pressure will be recorded and for detection of stigmata of chronic liver disease
Abdominal examination will be done for assessment of the size of the liver and spleen
3 Diagnosis of NAFLD
The diagnosis will be based on abdominal ultrasound findings and will be confirmed by fibroscan examination as the following
1 Abdominal ultrasound steatosis will be graded according to Quinn and Gosink 1985 as the following
Grade I Minimal diffuse increase in the fine echoes Liver appears bright compared to the cortex of the kidney
Grade II Moderate diffuse increase in the fine echoes Slightly impaired visualization of the intrahepatic vessels and diaphragm
Grade III Marked increase in the fine echoes Poor or no visualization of intrahepatic vessels and diaphragm and poor penetration of the posterior segment of the right lobe of the liver
2 Fibosscan to evaluate steatosis grades by CAP score and fibrosis stages as described by Sasso et al 2010
4 Laboratory investigations
1 Complete Blood Count CBC
2 Liver profile alanine aminotransferase ALT aspartate aminotransferase AST serum albumin total and direct bilirubin prothrombin time and INR
3 Renal profile creatinine and urine analysis
4 Total cholesterol triglyceride TG high-density lipoprotein cholesterol HDL-C low-density lipoprotein cholesterol LDL-C
5 Fasting blood sugar
6 HBsAg HCV Ab Viral markers
7 25-hydroxyl-vitamin D 25OHD in serum
8 Serum Osteocalcin as a marker of bone formation and serum NTX as a marker of bone resorption
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None