Hepatitis C (HCV) Cure and Kidney Health

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to learn how 12 weeks of HCV treatment with elbasvir and grazoprevir (brand name Zepatier) impacts your kidney function.

Detailed Description
-----------------
Prospective data collection of 25 Genotype 1 or 4 HCV-infected women from the San Francisco Women's Interagency HIV Study (WIHS) site and 25 Genotype 1 or 4 HCV-infected men from the San Francisco VA Medical Center who are initiated on Zepatier for 12 weeks (Total n=50). For women and men with HCV genotype 1a infection, only those without baseline NS5A resistance mutations will be included. Blood/urine samples will be collected before initiation of treatment, 4 weeks after treatment initiation, 12 weeks after treatment initiation (end of treatment), 24 weeks after treatment initiation to determine Sustained Virological Response (SVR), and at 48 weeks after treatment initiation.

Official Title
-----------------
HCV Cure and Kidney Health: A Prospective, Observational Cohort Study of HCV Genotype 1 and 4 Infected Adults With and Without HIV Infection

Conditions
-----------------
Hepatitis C

Intervention / Treatment
-----------------
* Drug: Elbasvir / Grazoprevir Oral Tablet [Zepatier]


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Active Genotype 1 or 4 HCV infection (If with Genotype 1a infection, only those without baseline NS5A resistance mutation will be included; Genotype 4 HCV infection is uncommon in both study populations). Subjects with HIV coinfection are included. We will not exclude patients who have severe Chronic Kidney Disease, are on dialysis, or have undergone kidney transplant. Exclusion Criteria: HCV genotype 2, 3, 5, or 6 infection Previous virologic failure to regimens containing an NS5A inhibitor Decompensated liver disease (Child-Pugh Class B or C) Albumin below 3g/dL Platelet count below 75,000 Any condition that the investigator considers a contraindication to study participation including limited life expectancy Pregnant or breastfeeding woman Hepatitis B virus (HBV) surface antigen positive (Note: Patients positive for the HBV core antibody will not be excluded, but will have HBV DNA levels checked and will be monitored while on Direct Acting Antivirals (DAA) therapy and medically managed as considered appropriate) Documented ongoing nonadherence to prescribed medications or medical treatment, failure to complete HCV disease evaluation appointments and procedures or unable to commit to scheduled followup/monitoring for the duration of treatment Poor venous access not allowing screening laboratory collection Known hypersensitivity to elbasvir/grazoprevir Co-administration with drugs that are 1) strong CYP3A inducers (e.g., phenytoin, carbamazepine, rifampin); 2) OATP1B1/3 inhibitors (e.g., cyclosporine, darunavir, atazanavir, tipranavir, lopinavir or saquinavir) or 3) efavirenz

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Elbasvir / Grazoprevir Oral Tablet [Zepatier]|HCV treatment|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glomerular filtration rate and injury | measured by Cystatin C | 1 year | 
| glomerular filtration rate and injury | measured by Creatinine | 1 year | 
| glomerular filtration rate and injury | measured by albuminuria | 1 year | 
| Tubule dysfunction | measured by α1-microglobulin | 1 year | 
| Tubule dysfunction | measured by beta2-microglobulin | 1 year | 
| Tubule injury | measured by Interleukin-18 | 1 year | 
| tubule injury | measured by Kidney injury molecule-1 | 1 year | 
| tubule injury | measured by Neutrophil gelatinase-associated lipocalcin (NGAL) | 1 year | 
| tubule injury | measured by Clusterin | 1 year | 
| tubule injury | measured by Trefoil factor-3 (TFF-3) | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HCV clearance | measured by HCV viral load | 1 year | 
| liver fibrosis | liver stiffness measured by transient elastography | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
genotype 1, genotype 4