Antivirals Safe for HCV After Kidney Transplant

October 10, 2016

With new direct-acting antiviral agents, a rapid virological response was observed in a majority of patients.

New direct-acting antiviral agents (DAAs) are efficient and safe for treating patients with hepatitis C virus (HCV) infection after kidney transplantation, according to a study.

Common in kidney transplant recipients, HCV infection leads to decreased survival and kidney allografts, increased liver fibrosis, increased infection rates, new-onset diabetes mellitus, and cardiovascular disease. No anti-HCV therapy is approved in this setting.

“Until now, there has been no efficient and safe therapy to eliminate HCV infection after kidney transplantation,” stated the researchers, led by Nassim Kamar of the Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France. “New-generation DAAs (sofosbuvir combined with daclatasvir, simeprevir, or ledipasvir, with or without ribavirin) have been shown to be highly efficient in treating HCV infection in cirrhotic and non-cirrhotic immunocompetent patients, liver transplant recipients, and a combined liver–kidney transplant recipients with fibrosing cholestatic hepatitis.”

Kamar and colleagues conducted a pilot study to assess the efficacy and safety of an interferon-free sofosbuvir-based regimen to treat HCV RNA-positive kidney transplant recipients. The study included 25 kidney transplant recipients with chronic HCV infection; 19 patients received treatment for 12 weeks and 6 patients for 24 weeks. Three patients received sofosbuvir plus ribavirin, 4 patients received sofosbuvir plus daclatasvir, 1 patient received sofosbuvir plus simeprevir with ribavirin and 6 others without ribavirin, 1 patient received sofosbuvir plus ledipasvir with ribavirin and 9 others without ribavirin, and 1 patient received sofosbuvir plus pegylated-interferon plus ribavirin.

“We found that a rapid virological response, defined by undetectable viremia at week 4 after starting DAA therapy, was observed in 88% of patients; all patients were cleared of the virus after completion of therapy; the SVR was 100% at 12 weeks after completing therapy; and anti-HCV therapy was safe and no drug-drug interactions were observed,” they stated.

They added: “Our data show that a sofosbuvir-based anti-HCV therapy was extremely efficient at treating HCV infection after kidney transplantation. These results are quite similar to those observed for liver transplant recipients.” Interestingly, they noted that initial virological response and the SVR were similar in cirrhotic and non-cirrhotic patients.

The tolerance to the sofosbuvir-based therapy was excellent in kidney transplant recipients. “In contrast to previous findings, when interferon was used in this setting, there was no significant change in kidney function, and there were no acute rejections or graft losses,” they stated.

Immunosuppressive drug levels were strictly monitored, and there was no significant change in the dose of immunosuppressive drug that was needed during sofosbuvir therapy, including simeprevir, which is a protease inhibitor.

No adverse event was observed, but there was a significant decrease in calcineurin inhibitor levels observed after HCV clearance, they noted. This finding replicates those in previous studies that showed kidney transplant recipients with HCV replication had altered pharmacokinetics of calcineurin inhibitors with increased drug exposure. They warned physicians to tightly monitor calcineurin inhibitors and adjust their doses during antiviral therapy and after HCV clearance to avoid an acute rejection episode.

The researchers published their results in the May 2016 American Journal of Transplantation.