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

Sponsor

Icahn School of Medicine at Mount Sinai (Other)

Overall Status

Completed

CT.gov ID

NCT02718573

Collaborator

(none)

Enrollment

Location

35.3

Actual Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
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 Design

Study Type:

Observational

Actual Enrollment :

74 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Jan 1, 2015

Actual Primary Completion Date :

Dec 11, 2017

Actual Study Completion Date :

Dec 11, 2017

Arms and Interventions

Arm	Intervention/Treatment
Non-liver transplants with HCV
Liver transplants with HCV

Outcome Measures

Primary Outcome Measures

cytometry time of flight (CyTOF) [up to week 14]
the profile of immune cells in blood as assessed by cytometry time of flight (CyTOF) multiparameter analysis

Secondary Outcome Measures

CD8 T cells [Baseline and week 14]
Change in the percentage of CD8 Tcells level
HCV resistance mutations [up to week 14]
Incidence of emergence of HCV resistance mutations

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)