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 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.

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)