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

Completed
Conditions
Hepatitis C
HCV
Liver Transplant
Registration Number
NCT02718573
Lead Sponsor
Icahn School of Medicine at Mount Sinai
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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
74
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
HCV resistance mutationsup to week 14

Incidence of emergence of HCV resistance mutations

CD8 T cellsBaseline and week 14

Change in the percentage of CD8 Tcells level

Trial Locations

Locations (1)

Icahn School of Medicine at Mount Sinai

🇺🇸

New York, New York, United States

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