eGFR Evolution in HCV Patients Receiving SOF-based or SOF-free DAAs

Study Overview
=================
Brief Summary
-----------------
Data regarding the nephrotoxicity of sofosbuvir (SOF) remain controversial. The investigators compared the changes of estimated glomerular filtration rate (eGFR) in patients with chronic hepatitis C virus (HCV) infection receiving SOF-based or SOF-free direct acting antivirals (DAAs).

Detailed Description
-----------------
Chronic hepatitis C virus (HCV) infection is a major health problem that affects 71 million people worldwide. Patients with chronic HCV infection may present with various hepatic and extrahepatic manifestations which lead to substantial morbidity and mortality. In contrast, the long-term health outcome improves following successful HCV eradication by antiviral therapies. Owing to the excellent efficacy and safety as well as the short treatment duration, the use of interferon (IFN)-free direct acting antivirals (DAAs) has become the standard-of-care for managing HCV. Sofosbuvir (SOF) is a pyrimidine nucleotide analogue which acts as the HCV ribonucleic acid (RNA) chain terminator by inhibiting HCV non-structural protein 5B (NS5B) RNA-dependent RNA polymerase following intrahepatic activation to uridine triphosphate form. Dephosphorylation results in the formation of inactive metabolite (GS-331007) that undergoes extensive renal excretion. Clinically, SOF is administered once-daily with pangenotypic potency, well tolerability and a high genetic barrier to drug resistance. Furthermore, SOF can be used in combination with NS3/4A protease inhibitors (PIs), NS5A inhibitors, and/or ribavirin (RBV) to achieve high rates of sustained virologic response (SVR). Therefore, applying SOF-based DAAs for HCV is welcome to most treating physicians. Following the widespread use of SOF-based DAAs for treating HCV in different populations, a large-scale real-world HCV-TARGET study enrolling 1,789 patients indicated that patients with a baseline eGFR ≤ 45 mL/min/1.73m2 were associated with a higher risk of worsening renal function than those with a baseline eGFR > 45 mL/min/1.73m2 following SOF-based DAAs. Moreover, three retrospective studies showed that SOF-based DAAs negatively affected the on-treatment and off-therapy eGFR. On the contrary, other studies showed that the use of SOF-based DAAs did not worsen the eGFR. Because most studies were retrospective in nature without protocol-defined time point for eGFR assessment or patient election, and did not enroll patients receiving SOF-free DAAs as the controls, the investigators thus conducted a prospective study to evaluate the evolution of eGFR in patients with chronic HCV infection receiving SOF-based or SOF-free DAAs.

Official Title
-----------------
Evolution of Estimated Glomerular Filtration Rate in Chronic Hepatitis C Patients Receiving Sofosbuvir-based or Sofosbuvir-free Direct Acting Antivirals

Conditions
-----------------
Hepatitis C, Renal Disease, Viral Hepatitis C

Intervention / Treatment
-----------------
* Drug: Sofosbuvir / Velpatasvir Oral Tablet
* Drug: Sofosbuvir and Ledipasvir
* Drug: Sofosbuvir Tablets
* Drug: Ombitasvir/paritaprevir/ritonavir
* Drug: Elbasvir / Grazoprevir Oral Tablet
* Drug: Glecaprevir and Pibrentasvir


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Chronic HCV patients receiving SOF-based or SOF-free DAAs for 12 weeks Exclusion Criteria: Decompensated cirrhosis (Child-Pugh B or C) Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 Active hepatocellular carcinoma (HCC) Organ transplantation Hepatitis B virus (HBV) co-infection Human immunodeficiency virus (HIV) co-infection Not received off-therapy follow-up till week 24

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

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

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

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

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| SOF-based DAAs<br>Patients receiving sofosbuvir (SOF)-based direct acting antiviral agents (DAAs) for 12 weeks | Drug: Sofosbuvir / Velpatasvir Oral Tablet<br>* Sofosbuvir/velpatasvir for 12 weeks<br>* Other names: Epclusa;Drug: Sofosbuvir and Ledipasvir<br>* Sofosbuvir and ledipasvir for 12 weeks<br>* Other names: Harvoni;Drug: Sofosbuvir Tablets<br>* Sofosbuvir plus ribavirin (RBV) or daclatasvir (DCV) for 12 weeks<br>* Other names: Solvadi;|
| SOF-free DAAs<br>Patients receiving sofosbuvir (SOF)-free direct acting antiviral agents (DAAs) for 12 weeks | Drug: Ombitasvir/paritaprevir/ritonavir<br>* Ombitasvir/paritaprevir/ritonavir for 12 weeks<br>* Other names: Viekirax/exviera;Drug: Elbasvir / Grazoprevir Oral Tablet<br>* Elbasvir/grazoprevir for 12 weeks<br>* Other names: Zepatier;Drug: Glecaprevir and Pibrentasvir<br>* Glecaprevir/pibrentasvir for 12 weeks<br>* Other names: Maviret;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Slope differences of eGFR | Slope differences of eGFR between SOF-based and SOF-free DAAs | Baseline to off-therapy week 24 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Viral hepatitis C, Glomerular filtration rate, Direct acting antiviral agent, Sofosbuvir