Impact of Interferon-free Treatment for Hepatitis C Virus (HCV) on Blood Cells and Factors in Blood

The objectives of the study are to determine the impact of interferon-free treatment for the hepatitis C virus (HCV) on peripheral blood immune cell phenotype and soluble immune-related proteins in blood, while controlling for genetic polymorphisms known to impact HCV-related immune responses, and to determine the impact of the therapy on the emergence of drug-resistant HCV. The study design is informed by the researchers recent investigations of patients receiving HCV treatment. About 4% of patients who had not undergone liver transplantation experienced hepatic decompensating or another serious event. There were several cases of bacterial infection and two cases with elevated markers of autoimmune processes. These events suggest that treatment altered immune responses. About 25% of patients who had undergone liver transplantation experienced hepatic decompensating or another serious adverse event. The long term goal is to understand the pathophysiology of these complications and determine whether HCV treatment can cause an immune reconstitution syndrome in susceptible patients, while improving antimicrobial defenses in others

Study Overview

• Status: Completed
• Conditions: Hepatitis C; HCV; Liver Transplant

Detailed Description

The objectives of the study are to determine the impact of interferon-free treatment for the hepatitis C virus (HCV) on peripheral blood immune cell phenotype and soluble immune-related proteins in blood, while controlling for genetic polymorphisms known to impact HCV-related immune responses, and to determine the impact of the therapy on the emergence of drug-resistant HCV. The study design is informed by the researchers' recent investigations of patients receiving HCV treatment. About 4% of patients who had not undergone liver transplantation experienced hepatic decompensation or another serious event. There were several cases of bacterial infection and two cases with elevated markers of autoimmune processes. These events suggest that treatment altered immune responses. About 25% of patients who had undergone liver transplantation experienced hepatic decompensation or another serious adverse event. The long term goal is to understand the pathophysiology of these complications and determine whether HCV treatment can cause an immune reconstitution syndrome in susceptible patients, while improving antimicrobial defenses in others The main questions/objectives to be addressed are (1) to determine the effect of HCV treatment on the profile of immune cells in blood as assessed by cytometry time of flight (CyTOF) multiparameter analysis, while controlling for genetic polymorphisms known to be associated with HCV-related immune responses and, (2) to determine the effect of treatment on factors/proteins in blood that may be related to immunity and inflammation.

Background: New treatments for HCV are significantly more effective than past treatments. They utilize direct acting antiviral drugs (DAA) and many do not include interferon. The goal of treatment is to achieve a sustained virological response (SVR). An SVR is indicated by the absence of detectable HCV RNA in blood 12 weeks after the end of treatment (EOT); this is called SVR12. The researchers recently investigated outcomes of 514 non-liver transplant (LT) patients and 43 LT patients who initiated treatment between Dec 2013 and June 2014. Several patients developed increased levels of markers of autoimmune processes and/or experienced a bacterial infection. Investigators at other institutions recently reported evidence that DAA treatment enhances immune cell activation. The combination of the investigators' observations and the observations of others indicates that a detailed investigation is needed to understand the events leading to increased immune cell activity and to determine the factors that may increase the risk of serious adverse events.

• Study Type: Observational
• Enrollment (Actual): 74

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Patients will be identified by their health care providers, including the co-investigators, who will describe the study to potential participants and inform the research team of patients who are interested in participating.

Description

Inclusion for non-LT patients:

• Adult
• Not pregnant
• Positive test for HCV RNA and planning to start interferon-free treatment soon
• Not HIV infected
• Able and willing to travel to Mount Sinai at the time points need for blood draws--prior to the start of treatment (within one month of the actual start date), at the 4th week of treatments (plus or minus two weeks), at the 12th week of treatment (plus or minus two weeks).
• Must understand and speak English
• Medically stable
• Willing to sign informed consent and participate

Inclusion criteria for LT patients:

• All of the above
• At least 6 months post-LT
• On stable immunosuppressive medications for at least 3 months LT only (no other organ transplant, such as kidney)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Non-liver transplants with HCV
Liver transplants with HCV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cytometry time of flight (CyTOF)	the profile of immune cells in blood as assessed by cytometry time of flight (CyTOF) multiparameter analysis	up to week 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CD8 T cells	Change in the percentage of CD8 Tcells level	Baseline and week 14
HCV resistance mutations	Incidence of emergence of HCV resistance mutations	up to week 14

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Andrea D. Branch, PhD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): December 11, 2017
• Study Completion (Actual): December 11, 2017

Study Registration Dates

• First Submitted: March 18, 2016
• First Submitted That Met QC Criteria: March 18, 2016
• First Posted (Estimate): March 24, 2016

Study Record Updates

• Last Update Posted (Actual): January 18, 2018
• Last Update Submitted That Met QC Criteria: January 16, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Hepatitis C; Interferon-free; DDA's
• 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; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C
• Other Study ID Numbers: GCO 14-2222

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES