Deciphering the Mechanisms Involved in Microbial Translocation Across the Spectrum of HCV Associated Liver Fibrosis
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|ClinicalTrials.gov Identifier: NCT02400216|
Recruitment Status : Completed
First Posted : March 27, 2015
Last Update Posted : October 22, 2021
- Hepatitis C infection (HCV) is a leading cause of liver disease. Normal bacteria from the intestines may spread to the liver and blood during liver disease. This is called bacterial translocation (BT). Researchers think BT may cause liver disease to worsen.
- To study the mechanisms involved in BT in early and advanced liver disease. To find out whether BT causes liver disease to worsen.
- People over age 18 with HCV and clinically stable liver disease.
- Participants will be screened with medical history and physical exam. They will have blood tests and imaging studies.
- Participants will have 2 outpatient visits and a 3-day stay at the clinic.
- At visit 1, participants will have urine and blood tests. They will have a magnetic resonance imaging (MRI) scan. A solution will be injected into a vein. The MRI scanner is a metal cylinder surrounded by a magnetic field. The participant will lie on a table that slides in and out of the cylinder.
- At visit 2, a substance will be injected into a vein and swallowed. Participants will then have blood drawn 5 times over 90 minutes.
- During the inpatient stay, serial blood tests will be drawn.
- Participants will give 2 stool samples and have another MRI.
- A needle will be inserted through the chest wall into a vein inside the liver, guided by ultrasound. The blood pressure inside this vein will be measured and blood will be drawn from it. About 1 inch of liver tissue will be removed.
- A study investigator will call participants to discuss all test results.
|Condition or disease|
Hepatitis C (HCV) is a leading cause of cirrhosis worldwide. Most complications associated with cirrhosis are driven by an altered portal circulation and the development of portal hypertension. Bacterial translocation (BT) from the gut to the systemic circulation is considered a pivotal mechanism contributing to the development of life-threatening complications in end stage cirrhosis. Recent evidence suggests that the liver and systemic circulation may be exposed to gut derived microbial products at earlier stages of liver disease. This early exposure may trigger hepatic inflammation, modify immune host response and accelerate hepatic fibrogenesis; which, in turn, impairs portal inflow, alters the portal circulation, and leads to development of portal hypertension. The mechanisms resulting in systemic exposure to gut derived microbial products, and the subsequent host response to BT has not been studied in patients with early liver disease nor fully compensated cirrhosis.
We therefore intend to enroll 30 chronic HCV patients with either cirrhosis (20) or minimal liver fibrosis (10). Study participants will undergo extensive evaluation with portal vein sampling and pressure measurements, dual cholate clearances, liver biopsy, serologic, immunologic, fecal microbiome and imaging studies. This will be followed by an optional second percutaneous liver biopsy and portal vein sampling 9-15 months after HCV treatment. The treatment protocol is a separate independent protocol, 15-DK- 0143 utilizing Sofosbuvir and GS-5816. The goals of our study are to characterize the extent of BT in early stages of cirrhotic and non-cirrhotic liver disease, explore the mechanisms contributing to its occurrence and identify potential serological, immunological and hemodynamic biomarkers associated with chronic infection. This, in turn, can aid in establishing a possible link between BT, subsequent host responses and severity of liver disease.
|Study Type :||Observational|
|Actual Enrollment :||30 participants|
|Official Title:||A Multidisciplinary Approach to Deciphering the Mechanisms Involved In Microbial Translocation Across the Spectrum of HCV Associated Liver Fibrosis|
|Actual Study Start Date :||May 29, 2015|
|Actual Primary Completion Date :||February 24, 2017|
|Actual Study Completion Date :||April 25, 2017|
Patients with fibrosis levels spanning from bridging fibrosis to cirrhosis (Ishak fibrosis score 5-6)
Patients with minimal fibrosis (Ishak score 0-1).
- Microbial product detection rate [ Time Frame: Before anti viral therapy and 9-15 months after treatment ]Assess the extent of BT, explore possible mechanisms accounting for its occurrence and evaluate its effects on the immune system in different stages of liver fibrosis
- Dual-cholate liver function tests [ Time Frame: Baseline, and 9-15 months after treatment ]Comparison of dual-cholate liver function tests and its association with microbial product levels in portal and systemic blood, between group A and group B patients.
- SPIO-MRI Kupffer cell uptake [ Time Frame: Baseline, and 9-15 months after treatment ]Comparison of SPIO-MRI Kupffer cell uptake values and its association with microbial product levels in portal and systemic blood between group A and group B patients.
- Immune activation markers [ Time Frame: Baseline, and 9-15 months after treatment ]Comparison of immune activation markers to bacterial products in liver tissue between group A and group B patients before and after HCV treatment.
- Pro and anti-inflammatory gene transcription [ Time Frame: Baseline, and 9-15 months after treatment ]Comparison of pro and anti-inflammatory gene transcription analysis in between group A and group B patients
- Fecal microbiome [ Time Frame: Baseline, and 9-15 months after treatment ]Comparison of fecal microbiome analysis between group A and group B patients
- Species homology [ Time Frame: Baseline, and 9-15 months after treatment ]Evaluation of species homology between microbial DNA identified in portal and systemic blood and fecal samples by deep sequencing.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02400216
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Theo Heller, M.D.||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|