Intervention: Zepatier
Trial phase: Phase 4
ATC code: J05AP54
SMILES: C=CC1CC1(NC(=O)C1CC2CN1C(=O)C(C(C)(C)C)NC(=O)OC1CC1CCCCCc1nc3ccc(OC)cc3nc1O2)C(=O)NS(=O)(=O)C1CC1.COC(=O)NC(C(=O)N1CCCC1c1ncc(-c2ccc3c(c2)cc2n3C(c3ccccc3)Oc3cc(C4=NC(C5CCCN5C(=O)C(NC(=O)OC)C(C)C)N=C4)ccc3-2)[nH]1)C(C)C
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 21
Group description: This arm will evaluate the treatment of patients with HCV and chronic kidney disease (GFR <50) who have had a kidney transplant using grazoprevir and elbasvir.

Post-transplant Grazoprevir and Elbasvir: Treatment will be started in the post-transplant patients on day 0 with the combination pill zepatier, containing grazoprevir 100mg/elbasvir 50mg by mouth once daily. The medications will be continued for a total of 12 weeks (16 weeks if resistance mutations, RAVs, are detected)
Eligibility criteria:
Inclusion Criteria:

At least 18 years of age at the time of screening
Have stable renal function for one month (30 days) prior to enrollment
Have Chronic HCV infection prior to transplantation with documented HCV viremia ≥ 1,000 IU/ml at screening and either documented HCV Ab positivity or HCV viremia ≥ 1,000 IU/ml at least 6 months prior to enrollment.
Documented genotype 1 HCV infection prior to enrollment and after their transplant in the post-transplantation cohort
HCV disease staging within 12 months prior to enrollment by liver biopsy, transient elastography, or biochemical testing
Be able to give informed consent and comply with study guidelines
Women of childbearing age will be required to have a negative pregnancy test at enrollment and use birth control throughout the duration of treatment.

Inclusion Criteria Specific to the Pre-transplant Arm

Patients will either be:

On the transplant waiting list followed by the University of Maryland's nephrology clinic or the Baltimore VA's nephrology clinic
On chronic hemodialysis not yet on the transplant list and followed in the University's hemodialysis center or in the University's nephrology clinic
Have chronic kidney disease with GFR <50

Inclusion Criteria Specific to the Post-transplant Arm

• Patients will have undergone renal transplantation no greater than five years prior to enrollment and will be followed in our University's nephrology and infectious disease clinic. They will all have stable renal function at the time of enrollment.

Exclusion Criteria:

Documented positive hepatitis B (HBV) surface antigen, and/or HBV DNA prior to enrollment
Any prior exposure to HCV protease inhibitor therapy
HIV co-infection if on a protease inhibitor based regimen
Increase in creatinine of 15% or greater within one month (30 days) of the screening visit
Evidence of hepatocellular carcinoma at the time of enrollment
Liver disease caused by an etiology other than HCV
F4 or decompensated cirrhotic patients
Child Pugh class B or C
AST or ALT >350 within 6 months prior to enrollment
Albumin < 3g/dL at the time of enrollment
Platelet count < 75 at the time of enrollment
History of clinically significant allergy or adverse event with protease inhibitors
Evidence of the acquisition of HCV at the time of or after transplantation
Pregnant or breastfeeding women
Cyclosporine; St. John's Wort; Efavirenz; Phenytoin; Carbamazepine; Bosentan; HIV protease inhibitors; modafinil; ketoconazole; or rifampin use within 7 days of enrollment
Coadministration of more than 20 mg atorvastatin; 10 mg rosuvastatin; 20 mg of fluvastatin, lovastatin or simvastatin