In the Journals

Epclusa safe, effective post-liver transplant for HCV genotypes 1-4

Patients with hepatitis C genotype 1 through 4 who underwent liver transplantation had significantly high rates of sustained virologic response after treatment with Epclusa for 12 weeks, regardless of cirrhosis status, according to recently published data.

“Among HCV-infected liver transplant recipients, HCV recurrence emerges in nearly all patients,” Kosh Agarwal, MD, from Kings College Hospital, United Kingdom, and colleagues wrote. “Within 5 years posttransplant, cirrhosis related to HCV ensues in approximately 30% of patients with recurrent, chronic HCV infection and is associated with increased graft loss rates and death. In the setting of posttransplant immunosuppression, the rate of hepatic fibrosis is accelerated in HCV-infected patients compared to the pretransplant period.”

The study comprised 79 patients with HCV who underwent treatment with Epclusa (sofosbuvir/velpatasvir [SOF/VEL], Gilead Sciences) posttransplant, including 37 patients with genotype 1, three patients with genotype 2, 35 patients with genotype 3 and four patients with genotype 4.

Additionally, 14 patients had cirrhosis and 47 patients were treatment-experienced with direct-acting antivirals, interferon or pegylated interferon with or without ribavirin.

The overall SVR rate was 97%. By genotype, the rates were 96% for genotype 1, 100% for genotype 2, 97% for genotype 3 and 100% for genotype 4.

Two patients experienced virologic relapse and one patient experienced a nonvirologic failure. No patients experienced on-treatment virologic failure.

The researchers found no significant clinical effect on sustained virologic response after subanalyses by age, sex, cirrhosis status or treatment experience.

Of the 78 patients included in a resistance subanalysis, 92% of patients with baseline NS5A resistance-associated substitutions achieved SVR at 12 weeks including all three patients with genotype 3a and Y93H. The six patients who had NS5B resistance-associated substitutions at baseline also achieved SVR.

Regarding safety, one patient with a history of diabetes discontinued treatment due to an adverse event of hyperglycemia. The remaining patients completed treatment.

“Treatment was well-tolerated with ... no episodes of rejection, and no adjustments to immunosuppression to manage suspected drug-drug interactions. These results occurred in the setting of no restrictions on concomitant immunosuppression therapy allowed in this study,” Agarwal and colleagues wrote. “Importantly, no drug interactions between SOF/VEL and immunosuppressant medications are anticipated. These features make SOF/VEL well suited to address the unmet medical needs of liver transplant recipients.” – by Talitha Bennett

Disclosure: Agarwal reports he received grant support from AbbVie, Bristol-Myers Squibb, Gilead and Merck Sharp & Dohme. Please see the full study for the other authors’ relevant financial disclosures.

Patients with hepatitis C genotype 1 through 4 who underwent liver transplantation had significantly high rates of sustained virologic response after treatment with Epclusa for 12 weeks, regardless of cirrhosis status, according to recently published data.

“Among HCV-infected liver transplant recipients, HCV recurrence emerges in nearly all patients,” Kosh Agarwal, MD, from Kings College Hospital, United Kingdom, and colleagues wrote. “Within 5 years posttransplant, cirrhosis related to HCV ensues in approximately 30% of patients with recurrent, chronic HCV infection and is associated with increased graft loss rates and death. In the setting of posttransplant immunosuppression, the rate of hepatic fibrosis is accelerated in HCV-infected patients compared to the pretransplant period.”

The study comprised 79 patients with HCV who underwent treatment with Epclusa (sofosbuvir/velpatasvir [SOF/VEL], Gilead Sciences) posttransplant, including 37 patients with genotype 1, three patients with genotype 2, 35 patients with genotype 3 and four patients with genotype 4.

Additionally, 14 patients had cirrhosis and 47 patients were treatment-experienced with direct-acting antivirals, interferon or pegylated interferon with or without ribavirin.

The overall SVR rate was 97%. By genotype, the rates were 96% for genotype 1, 100% for genotype 2, 97% for genotype 3 and 100% for genotype 4.

Two patients experienced virologic relapse and one patient experienced a nonvirologic failure. No patients experienced on-treatment virologic failure.

The researchers found no significant clinical effect on sustained virologic response after subanalyses by age, sex, cirrhosis status or treatment experience.

Of the 78 patients included in a resistance subanalysis, 92% of patients with baseline NS5A resistance-associated substitutions achieved SVR at 12 weeks including all three patients with genotype 3a and Y93H. The six patients who had NS5B resistance-associated substitutions at baseline also achieved SVR.

Regarding safety, one patient with a history of diabetes discontinued treatment due to an adverse event of hyperglycemia. The remaining patients completed treatment.

“Treatment was well-tolerated with ... no episodes of rejection, and no adjustments to immunosuppression to manage suspected drug-drug interactions. These results occurred in the setting of no restrictions on concomitant immunosuppression therapy allowed in this study,” Agarwal and colleagues wrote. “Importantly, no drug interactions between SOF/VEL and immunosuppressant medications are anticipated. These features make SOF/VEL well suited to address the unmet medical needs of liver transplant recipients.” – by Talitha Bennett

Disclosure: Agarwal reports he received grant support from AbbVie, Bristol-Myers Squibb, Gilead and Merck Sharp & Dohme. Please see the full study for the other authors’ relevant financial disclosures.