Liver transplant recipients with HCV fare well under drug combo

For post-liver transplant recipients infected with hepatitis C virus (HCV), a combination of ledipasvir and sofosbuvir without ribavirin yields excellent outcomes and favorable safety and tolerability profiles, according to a new study.

Current guidelines recommend including ribavirin when treating post-transplant patients because of a lack of efficacy data of therapies without ribavirin.

“This study, the largest single-center experience of post-liver transplant patients with HCV genotype 1 recurrence taking direct-acting antivirals (DAAs) without ribavirin, is uniquely designed to determine the effectiveness of DAAs in post-transplant patients without ribavirin,” Joel Wedd MD, MPH, assistant professor of medicine and director of the Liver Tumor Clinic at Atlanta-based Emory University Hepatology and Liver Transplantation, told Medical Economics.

This is particularly important because ribavirin has side effects, especially in the post-transplant population, he noted.

The researchers published their results in the June 2017 Alimentary Pharmacology & Therapeutics.

Next: Study details

Ledipasvir and sofosbuvir is a well-tolerated regimen with high sustained virological response (SVR) rates in pre-liver transplant patients infected with chronic HCV.

Wedd and colleagues conducted a retrospective study examining the treatment of post-liver transplant recipients with ledipasvir and sofosbuvir without ribavirin. They analyzed the differences between SVR cohorts and predictors of SVR.

A total of 408 genotype-1 HCV patients were treated with ledipasvir/sofosbuvir from October 2014 to August 2015 at Emory University; 73 patients had received a liver transplant and were treated for a median of 2.9 years post-transplant. About two-thirds of patients were treated previously, including 13.7% of patients previously treated with DAAs.

“Despite the lack of ribavirin, patients achieved a SVR rate at 12 weeks of 96%, comparable to rates found in controlled trials and to those including ribavirin,” said Wedd.

Only 2.7% of patients had recurrent allograft cirrhosis, and the majority (90.4%) was on calcineurin inhibitor-based immunosuppressive therapy. Approximately 82% of patients had chronic kidney disease stage 2 or 3. In univariate logistic regression, only detectable week 8 viral load was predictive of failure to achieve SVR.

The biggest complication of taking ribavirin in post-liver transplant patients is anemia because it causes hemolysis. “This is exacerbated in liver transplant patients who take bone-marrow suppressing medications to reduce the risk of rejection. This complication can cause symptomatic anemia requiring transfusions, hospitalizations and increased management burden on the patient,” said Wedd.

Other potential ribavirin side effects include nausea and diarrhea. “Additionally, ribavirin is limited in patients with renal impairment, which is common in post-liver transplant patients. If ribavirin was not a necessary component of therapy for post-transplant patients, treatment risk and side-effects would be significantly reduced,” he said.

Wedd believes that guideline committees should recognize these study results without ribavirin and consider amending recommendations to omit ribavirin as a necessary component of genotype-1 HCV therapy in post-liver transplant patients.

“Primary care physicians should be aware of the side effects of ribavirin, especially in the post-liver transplant population, and that its use may be unnecessary in that setting,” said Wedd.