Study of Hepatic Responses in Patients Receiving Direct-acting Anti-HCV Drugs

This study is designed to obtain and store samples of serum and liver tissue in HCV (HepC Virus)-infected patients being treated with direct-acting antiviral (DAA) therapy, and to determine the effect of new DAA therapies on HCV-related responses in the liver and peripheral blood.

The introduction of new DAAs regimens that do not include IFN provides unique and novel opportunities to examine whether successful treatment-induced eradication of viral antigen results in reconstitution of T cell immunity. serum and liver tissue samples will be collected and stored in hopes of improving treatment and outcomes for future patients.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Procedure: Liver Biopsy

Detailed Description

This study is designed to obtain and store samples of serum and liver tissue in HCV-infected patients being treated with DAA therapy.

A liver biopsy will be performed pre-treatment for research reasons. A small liver sample that is not required for pathologic analysis will also be stored. Patients will undergo another liver biopsy at either 4 or 12 weeks after initiation of DAA therapy.

Any patients with HCV-related liver disease (age > 18) will be considered for this study.

Patients will have a 120 ml blood draw for research purposes at baseline and 12 weeks after stopping DAA treatment along with a 60 ml blood draw at 2, 4, 8, and 12 weeks of treatment.

The liver biopsy at baseline and then either at 4 or 12 weeks will be examined using molecular techniques to measure transcription of key genes involved in the antiviral response.

• Study Type: Observational
• Enrollment (Actual): 5

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Sandra Boimbo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Recruitment of patients will primarily occur through the Hepatology clinic, so non-veterans will be recruited. A total of 20 HCV-positive patients who will be treated with FDA-approved treatments as covered by the patient's insurance. Half of the patients will be treatment-naïve prior to enrollment and half will be treatment-experienced with either null response or relapse, i.e., persistent viremia. An equal proportion in each group will be biopsied at 4 versus 12 weeks after first dosing of DAA. Patients will be subjected to two biopsies during the life of the study.

Description

Inclusion Criteria

• Signed informed consent
• Ages 18-70
• HCV-infected patients being treated with direct-acting antiviral (DAA) therapy.

Exclusion Criteria

• Pregnant women or females of childbearing potential that are not on contraception
• Institutionalized or mentally disabled persons
• Prisoners
• Unwilling or unable to provide informed consent
• Subjects who are HIV positive
• Anticipated inability to follow up
• Chronic anemia
• Platelet count < 100 for liver biopsy patients who have documented fatty liver disease by ultrasound prior to enrollment
• Any patient with bleeding disorders or prolonged INR
• Abstinent or consuming less than two drinks of alcohol per day.
• Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients who will have their second Liver biopsy at week 4; The 4 week time point is performed in lieu of the 12 week and the purpose of this time point is to evaluate earlier responses and transcriptional changes that might predict viral clearance or treatment failure in a subset of patients.	Procedure: Liver Biopsy; patients will get a research liver biopsy pre-DAA treatment and either 4 or the standard 12 week time point. The liver biopsy is performed using standard protocol with ultrasound guidance.
Patients who will have their second Liver biopsy at week 12; Liver biopsies will be obtained at week 12 when most DAA treatments end in order to compare the hepatic responses induced or reduced by clearance of HCV	Procedure: Liver Biopsy; patients will get a research liver biopsy pre-DAA treatment and either 4 or the standard 12 week time point. The liver biopsy is performed using standard protocol with ultrasound guidance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in gene array from baseline to either 4 or 12 weeks after treatment.	To examine the effect of new DAA therapies on HCV-related responses in the liver and peripheral blood.	1 year

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Hugo Rosen, MD, University of Colorado, Denver

Publications and helpful links

General Publications

• Golden-Mason L, Palmer B, Klarquist J, Mengshol JA, Castelblanco N, Rosen HR. Upregulation of PD-1 expression on circulating and intrahepatic hepatitis C virus-specific CD8+ T cells associated with reversible immune dysfunction. J Virol. 2007 Sep;81(17):9249-58. doi: 10.1128/JVI.00409-07. Epub 2007 Jun 13.

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): July 10, 2018
• Study Completion (Actual): July 10, 2018

Study Registration Dates

• First Submitted: August 13, 2015
• First Submitted That Met QC Criteria: August 21, 2015
• First Posted (Estimate): August 26, 2015

Study Record Updates

• Last Update Posted (Actual): September 19, 2018
• Last Update Submitted That Met QC Criteria: September 17, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: HCV
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C
• Other Study ID Numbers: 14-1794; UL1TR001082 (U.S. NIH Grant/Contract)