Non-invasive Biomarkers of Fibrosis in Pediatric Liver Diseases
| Status: | Completed |
|---|---|
| Conditions: | Gastrointestinal, Gastrointestinal, Hepatitis, Hepatitis, Hepatitis |
| Therapuetic Areas: | Gastroenterology, Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | Any - 17 |
| Updated: | 7/20/2018 |
| Start Date: | October 2013 |
| End Date: | June 2016 |
Utility of Shearwave Elastography (SWE) and Non-Invasive Serum Biomarkers to Detect Fibrosis in Pediatric Patients With Liver Diseases
This study is being conducted to develop new techniques for early diagnosis of liver disease.
These techniques are: Shearwave Elastography (SWE) ultrasound and blood biomarkers.
SWE ultrasound uses high-frequency sound waves to view soft tissues such as muscles and
internal organs and measure stiffness. An ultrasound creates computer images that show
internal body organs, such as the liver or kidneys, more clearly than regular x-ray images.
Biomarkers are biological molecules found in the blood that provide important information
about liver disease.
These techniques are: Shearwave Elastography (SWE) ultrasound and blood biomarkers.
SWE ultrasound uses high-frequency sound waves to view soft tissues such as muscles and
internal organs and measure stiffness. An ultrasound creates computer images that show
internal body organs, such as the liver or kidneys, more clearly than regular x-ray images.
Biomarkers are biological molecules found in the blood that provide important information
about liver disease.
Abnormal liver biochemical and function tests are frequently detected in symptomatic patients
since many screening blood test panels routinely include them. A population-based survey in
the United States conducted between 1999 and 2002 estimated that an abnormal alanine
aminotransferase (ALT) was present in 8.9 percent of respondents. These patients are often
referred to hepatology to elucidate the cause of these abnormal liver tests and potential
liver disease. Identifying the cause of specific pediatric liver diseases is critical to the
management and treatment. Liver biopsy provides histological information often needed to make
a conclusive diagnosis and has historically been accepted as the best way to measure liver
fibrosis.
Given that the current gold standard for assessing for liver fibrosis is via liver biopsy,
there are several reasons why the field is looking for a non-invasive method that correlates
highly with liver histology. Hemorrhage, infection, the need to often be observed overnight,
anxiety, and need for sedation are the accepted risks for all liver biopsies. The histologic
grade on liver biopsy (grades 0-4) is used to grade the severity of hepatic fibrosis and make
clinical decisions such as initiating treatment with antiviral or immunomodulator therapy.
Ultrasound imaging (sonography) uses high-frequency sound waves to view soft tissues such as
muscles and internal organs, limited primarily by non-sound transmitting tissues such as air
and bone. Ultrasound is an excellent modality for the pediatric population and provides far
ranging diagnostic possibilities, limiting the use of radiation whenever possible. Sheerwave
elastography is a complimentary noninvasive, real-time sonographic technique that has been
shown to have a wide range of clinical applications, including the ability to assess the
degree of liver fibrosis in chronic liver disease. Tissue has an inherent elasticity which
may be altered by pathologic processes such as inflammation, fibrosis, and tumors.
Elastography has been used extensively in breast imaging showing much promise in detecting
non-compressible masses associated with an increased risk of malignancy. Elastography has the
ability to assess small changes in pliability of liver tissue across the entire liver.
Elasticity of tissue in the context of elastography is the ratio of tension (stress) needed
to produce a relative change in length (strain), and quantifies how much pressure must be
placed on tissue in order to cause elastic deformation. Ultrasonic elastography has been
performed to detect hepatic fibrosis in patients with fatty liver disease in adults, but not
yet in children with viral hepatitis B or C.
Performance compression ultrasound require no more than 5-10 additional minutes of imaging
and have no known associated risks.
Serum fibrosis markers are promising non-invasive indicators of fibrosis and progression to
cirrhosis in adult liver diseases: e.g. the commercially available Fibrotest® is used to
detect hepatic fibrosis in hepatitis C and in non-alcoholic fatty liver disease (NAFLD).
However, marker patterns appear to be disease and development (age) specific, making some of
the adult markers of doubtful value in children. As proof of principle, in a biopsy study of
another pediatric fibrosing liver entity, cystic fibrosis liver disease, specific marker
patterns derived from mechanistic studies were found to highly correlate with F3/4 fibrosis
vs F0/1.
The rapid onset of liver disease in some children (i.e. HBV, genotype C) indicates a need to
identify early markers of liver fibrosis to help facilitate early intervention. Serum
chemistries used to assess hepatic inflammation and injury are not reliable. Empirically
identified markers identified by genomic, proteomic, and metabolomic technologies, as well as
targeted serum marker analysis, offer new strategies with which to diagnose and predict
outcomes in pediatric liver diseases. Preliminary studies in children with fibrotic liver
diseases have identified specific markers reflecting matrix re-modeling, hepatic stellate
cell activation and chemoattractant expression in this age group.
since many screening blood test panels routinely include them. A population-based survey in
the United States conducted between 1999 and 2002 estimated that an abnormal alanine
aminotransferase (ALT) was present in 8.9 percent of respondents. These patients are often
referred to hepatology to elucidate the cause of these abnormal liver tests and potential
liver disease. Identifying the cause of specific pediatric liver diseases is critical to the
management and treatment. Liver biopsy provides histological information often needed to make
a conclusive diagnosis and has historically been accepted as the best way to measure liver
fibrosis.
Given that the current gold standard for assessing for liver fibrosis is via liver biopsy,
there are several reasons why the field is looking for a non-invasive method that correlates
highly with liver histology. Hemorrhage, infection, the need to often be observed overnight,
anxiety, and need for sedation are the accepted risks for all liver biopsies. The histologic
grade on liver biopsy (grades 0-4) is used to grade the severity of hepatic fibrosis and make
clinical decisions such as initiating treatment with antiviral or immunomodulator therapy.
Ultrasound imaging (sonography) uses high-frequency sound waves to view soft tissues such as
muscles and internal organs, limited primarily by non-sound transmitting tissues such as air
and bone. Ultrasound is an excellent modality for the pediatric population and provides far
ranging diagnostic possibilities, limiting the use of radiation whenever possible. Sheerwave
elastography is a complimentary noninvasive, real-time sonographic technique that has been
shown to have a wide range of clinical applications, including the ability to assess the
degree of liver fibrosis in chronic liver disease. Tissue has an inherent elasticity which
may be altered by pathologic processes such as inflammation, fibrosis, and tumors.
Elastography has been used extensively in breast imaging showing much promise in detecting
non-compressible masses associated with an increased risk of malignancy. Elastography has the
ability to assess small changes in pliability of liver tissue across the entire liver.
Elasticity of tissue in the context of elastography is the ratio of tension (stress) needed
to produce a relative change in length (strain), and quantifies how much pressure must be
placed on tissue in order to cause elastic deformation. Ultrasonic elastography has been
performed to detect hepatic fibrosis in patients with fatty liver disease in adults, but not
yet in children with viral hepatitis B or C.
Performance compression ultrasound require no more than 5-10 additional minutes of imaging
and have no known associated risks.
Serum fibrosis markers are promising non-invasive indicators of fibrosis and progression to
cirrhosis in adult liver diseases: e.g. the commercially available Fibrotest® is used to
detect hepatic fibrosis in hepatitis C and in non-alcoholic fatty liver disease (NAFLD).
However, marker patterns appear to be disease and development (age) specific, making some of
the adult markers of doubtful value in children. As proof of principle, in a biopsy study of
another pediatric fibrosing liver entity, cystic fibrosis liver disease, specific marker
patterns derived from mechanistic studies were found to highly correlate with F3/4 fibrosis
vs F0/1.
The rapid onset of liver disease in some children (i.e. HBV, genotype C) indicates a need to
identify early markers of liver fibrosis to help facilitate early intervention. Serum
chemistries used to assess hepatic inflammation and injury are not reliable. Empirically
identified markers identified by genomic, proteomic, and metabolomic technologies, as well as
targeted serum marker analysis, offer new strategies with which to diagnose and predict
outcomes in pediatric liver diseases. Preliminary studies in children with fibrotic liver
diseases have identified specific markers reflecting matrix re-modeling, hepatic stellate
cell activation and chemoattractant expression in this age group.
Inclusion Criteria:
- Patients with suspected or established liver disease
- Scheduled to have a clinically indicated liver biopsy
- Between the ages 0-17
Exclusion Criteria:
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