Identification of Inflammatory and Fibrotic Biomarkers in PBC and NAFLD Patients
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Gastrointestinal |
| Therapuetic Areas: | Gastroenterology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 3/23/2019 |
| Start Date: | May 2015 |
| End Date: | May 2019 |
Primary biliary cirrhosis (PBC) is a progressive autoimmune disease of biliary epithelial
cells resulting in biliary cirrhosis. PBC is characterized by a 90% female predominance, high
titers of serum anti-mitochondrial autoantibodies (AMA) directed against the pyruvate
dehydrogenase complex E2 subunit and evidence from both human and murine models suggests that
T-cells, particularly cluster of differentiation (CD) 8+ T cells, are key to the destruction
of bile ducts. However, clinical trials of classic immunosuppressive drugs including
corticosteroids, azathioprine, methotrexate, and tacrolimus have been largely unsuccessful in
altering the disease course. This is a single center, prospective, non-treatment study of the
role of immune responses in PBC patients.
Non-alcoholic fatty liver disease (NAFLD) and its more severe form, non-alcoholic
steatohepatitis (NASH) are common, often "silent" liver diseases. NASH resembles alcoholic
liver disease, but occurs in people who drink little or no alcohol. The major feature in NASH
is fat in the liver, along with inflammation and fibrosis. NASH can be severe and can lead to
cirrhosis and hepatocellular carcinoma. Ten to 20 percent of American have NAFLD with NASH
affecting 2 to 5 percent of Americans.
cells resulting in biliary cirrhosis. PBC is characterized by a 90% female predominance, high
titers of serum anti-mitochondrial autoantibodies (AMA) directed against the pyruvate
dehydrogenase complex E2 subunit and evidence from both human and murine models suggests that
T-cells, particularly cluster of differentiation (CD) 8+ T cells, are key to the destruction
of bile ducts. However, clinical trials of classic immunosuppressive drugs including
corticosteroids, azathioprine, methotrexate, and tacrolimus have been largely unsuccessful in
altering the disease course. This is a single center, prospective, non-treatment study of the
role of immune responses in PBC patients.
Non-alcoholic fatty liver disease (NAFLD) and its more severe form, non-alcoholic
steatohepatitis (NASH) are common, often "silent" liver diseases. NASH resembles alcoholic
liver disease, but occurs in people who drink little or no alcohol. The major feature in NASH
is fat in the liver, along with inflammation and fibrosis. NASH can be severe and can lead to
cirrhosis and hepatocellular carcinoma. Ten to 20 percent of American have NAFLD with NASH
affecting 2 to 5 percent of Americans.
In this study, the investigators will prospectively collect demographic, clinical, and
laboratory data and blood samples for research purposes on 45 PBC patients and 50 male and
female NAFLD patients. PBC and NAFLD diagnosis and clinical status will be evaluated by
magnetic resonance (MR) elastography, transient elastography (FibroScan®) and blood lab
analysis including anti-mitochondrial antibodies (AMA), anti-nuclear antibodies (ANA),
immunoglobulins, complete blood count (CBC), comprehensive metabolic panel (CMP) and
coagulation measures). Additionally serum and blood will be obtained from the patients on the
first visit and at months 3, 6, 9, 12, 15, 18, 21 & 24. Serum and blood samples will be used
to measure serum cytokine abundance and transcriptome analysis. For comparison, 95 age (+/- 5
years) and sex-matched controls without PBC will be recruited for a clinical laboratory,
cytokine, gene expression analysis. Control subjects will have blood drawn at a single time
point.
laboratory data and blood samples for research purposes on 45 PBC patients and 50 male and
female NAFLD patients. PBC and NAFLD diagnosis and clinical status will be evaluated by
magnetic resonance (MR) elastography, transient elastography (FibroScan®) and blood lab
analysis including anti-mitochondrial antibodies (AMA), anti-nuclear antibodies (ANA),
immunoglobulins, complete blood count (CBC), comprehensive metabolic panel (CMP) and
coagulation measures). Additionally serum and blood will be obtained from the patients on the
first visit and at months 3, 6, 9, 12, 15, 18, 21 & 24. Serum and blood samples will be used
to measure serum cytokine abundance and transcriptome analysis. For comparison, 95 age (+/- 5
years) and sex-matched controls without PBC will be recruited for a clinical laboratory,
cytokine, gene expression analysis. Control subjects will have blood drawn at a single time
point.
Inclusion Criteria for Primary Biliary Cirrhosis Group:
- PBC diagnosis based upon at least 2 of 3 criteria: AMA titer > 1:40; Alkaline
phosphatase > 1.5 times the upper limit of normal (ULN) for at least 6 months; and
Liver biopsy findings consistent with PBC
- 18 years of age and older.
Exclusion Criteria:
- Presence of other concomitant liver diseases including viral hepatitis, primary
sclerosing cholangitis (PSC), alcoholic liver disease, Wilson's disease,
hemochromatosis, or Gilbert's syndrome.
- Prior liver transplantation
- Use of immunosuppressants within 6 months of Day 0, including azathioprine,
prednisone, prednisolone, budesonide, cyclosporine, tacrolimus, methotrexate, or
mycophenolate mofetil.
- Use of biologic agents including anti-cell and anti-cytokine therapies within 12
months.
Inclusion Criteria for Control Subjects
- Absence of liver disease or inflammatory conditions
- 18 years of age and older.
Exclusion Criteria for Control Subjects
- Presence of concomitant liver diseases including PBC, viral hepatitis, PSC, alcoholic
liver disease, Wilson's disease, hemochromatosis, or Gilbert's syndrome.
- Prior liver transplantation
- Use of immunosuppressants within 6 months, including azathioprine, prednisone,
prednisolone, budesonide, cyclosporine, tacrolimus, methotrexate, or mycophenolate
mofetil.
- Use of biologic agents including anti-cell and anti-cytokine therapies within 12
months.
We found this trial at
1
site
2315 Stockton Blvd.
Sacramento, California 95817
Sacramento, California 95817
(916) 734-2011
Principal Investigator: Christopher L Bowlus, MD
Phone: 916-734-8696
University of California, Davis Medical Center UC Davis Medical Center serves a 65,000-square-mile area that...
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