Deciphering the Mechanisms Involved in Microbial Translocation Across the Spectrum of HCV Associated Liver Fibrosis

NCT02400216 | Completed FDA Drug

• 2 other identifiers: 15010015-DK-0100
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- 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. Objectives: \- To study the mechanisms involved in BT in early and advanced liver disease. To find out whether BT causes liver disease to worsen. Eligibility: \- People over age 18 with HCV and clinically stable liver disease. Design:

• 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.

Conditions

Cirrhosis

Keywords

Chronic Hepatitis C; Cirrhosis; Liver Biopsy; Microbiome; Natural History

Outcome Measures

Primary Outcomes (1)

• Microbial product detection rate

  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

  Before anti viral therapy and 9-15 months after treatment

Secondary Outcomes (6)

• Dual-cholate liver function tests

  Baseline, and 9-15 months after treatment

• SPIO-MRI Kupffer cell uptake

  Baseline, and 9-15 months after treatment

• Immune activation markers

  Baseline, and 9-15 months after treatment

• Pro and anti-inflammatory gene transcription

  Baseline, and 9-15 months after treatment

• Fecal microbiome

  Baseline, and 9-15 months after treatment

Study Arms (2)

Group A

Patients with fibrosis levels spanning from bridging fibrosis to cirrhosis (Ishak fibrosis score 5-6)

Drug: dual cholate

Group B

Patients with minimal fibrosis (Ishak score 0-1).

Drug: dual cholate

Interventions

dual cholate DRUG

test for defining disease severity

Group A; Group B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Primary clinical patients with chronic HCV infection divided into 2 groups according to liver fibrosis stage.

You may qualify if:

• All age greater than 18 male or female
• Capacity to provide written informed consent
• Evidence of HCV RNA in 2 serum samples at least 6 months apart.
• All HCV genotypes
• Liver biopsy in the last 2 years prior to enrollment showing Ishak fibrosis score of either 0-1 or 5-6. An alternative to liver biopsy will be a Fibroscan study performed in the 6 months prior to study enrollment showing a score of either kPa \<7 or above 13.
• Child-Pugh score less than or equal to 6
• Prior to each liver biopsy and portal vein cannulation procedure, blood will be drawn for CBC, PT/INR \& acute care panel.

You may not qualify if:

• Pregnant women or females at child bearing age not taking measures to prevent pregnancy during the period of study
• Patients currently on treatment for hepatitis C
• Clinical, serologic or histopathologic evidence supporting other etiologies of chronic liver disease besides HCV
• Current or past clinical evidence of decompensated liver disease (e.g. ascites, bleeding esophageal varices, spontaneous bacterial peritonitis, encephalopathy etc.)
• Cross sectional liver imaging study from the past 6 months showing a focal lesion suspicious of hepatocellular carcinoma and/or alpha-fetoprotein level greater than 200 ng/mL.
• Patients with active bacterial, viral or fungal, systemic or localized infection.
• Antibiotic treatment 30 days prior to study enrollment
• History of chronic inflammatory diseases of the bowel (Crohn s disease, Ulcerative colitis and celiac disease)
• History of congestive heart failure of moderate to severe degree.
• History of non-cirrhotic portal hypertension or portal vein thrombosis
• Patients with severe allergic reactions to iodine contrast, which cannot be controlled by premedication with antihistamines and steroids.
• Subjects with contraindication to MRI scanning. These contraindications include but are not limited to the following devices or conditions:
• \<TAB\>a. Implanted cardiac pacemaker or defibrillator
• \<TAB\>b. Cochlear Implants
• \<TAB\>c. Ocular foreign body (e.g. metal shavings)

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Oringher JL, Afruza R, Chakraborty M, Akiva KL, Zhang GY, Townsend EC, Quinn GM, Scheuing L, Menkart MG, Rai A, Kleiner DE, Levy EB, Koh C, Ali RO, Etzion O, Heller T. Portal Vein Tryptophan Pathway Analysis Reveals Gut-Mediated Inflammatory Pathway Predominance in HCV Infection. Liver Int. 2026 Apr;46(4):e70584. doi: 10.1111/liv.70584.

  PMID: 41804293 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Fibrosis; Hepatitis C, Chronic

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes

Study Officials

• Theo Heller, M.D.

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2015
• First Posted: March 27, 2015
• Study Start: May 29, 2015
• Primary Completion: February 24, 2017
• Study Completion: April 25, 2017
• Last Updated: April 29, 2026

Record last verified: 2026-03-31

Locations

US (1)