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Sofosbuvir/velpatasvir for 12 weeks in genotype 1-4 HCV-infected liver transplant recipients


Agarwal, Kosh; Castells, Lluís; Müllhaupt, Beat; Rosenberg, William M C; McNabb, Brian; Arterburn, Sarah; Camus, Gregory; McNally, John; Stamm, Luisa M; Brainard, Diana M; Mani Subramanian, G; Mariño, Zoe; Dufour, Jean-François; Forns, Xavier (2018). Sofosbuvir/velpatasvir for 12 weeks in genotype 1-4 HCV-infected liver transplant recipients. Journal of Hepatology, 69(3):603-607.

Abstract

BACKGROUND & AIMS Sofosbuvir, an NS5B inhibitor, combined with velpatasvir, an NS5A inhibitor (SOF/VEL), produces high sustained virologic response rates 12 weeks after treatment (SVR12) in patients with genotype 1-6 HCV infection, and has no anticipated clinically relevant drug-drug interactions with immunosuppressants. This study evaluated the safety and efficacy of SOF/VEL in adults with recurrent chronic genotype 1-4 HCV infection after liver transplant. METHODS Patients received SOF/VEL 400/100 mg daily for 12 weeks. Patients could be treatment experienced or treatment naïve with no cirrhosis or with compensated cirrhosis. The primary endpoints were SVR12 and discontinuations due to adverse events. RESULTS A total of 79 patients were enrolled and treated in this study (37 [47%] had genotype 1, 3 [4%] genotype 2, 35 [44%] genotype 3, and 4 [5%] genotype 4 HCV). Of these, 81% were male, 82% were white, 18% had compensated cirrhosis, and 59% were treatment experienced. The most commonly used immunosuppressants were tacrolimus (71%), mycophenolic acid (24%), cyclosporine (14%), and azathioprine (11%). Median (range) time from liver transplantation was 7.5 (0.3, 23.9) years. The SVR12 rate was 96%. By genotype, SVR12 rates were 95% (genotype 1), 100% (genotype 2), 97% (genotype 3), and 100% (genotype 4). Two patients experienced virologic relapse: one with genotype 1a infection was non-cirrhotic and treatment naïve, and one with genotype 3 infection was non-cirrhotic and treatment experienced. One patient discontinued SOF/VEL due to hyperglycemia. No serious or severe adverse events were deemed SOF/VEL-related by the investigator, and no liver transplant rejection episodes or deaths occurred during the study period. CONCLUSIONS Treatment with SOF/VEL for 12 weeks was highly effective and well tolerated in genotype 1-4 HCV-infected liver transplant recipients with and without cirrhosis. LAY SUMMARY Sofosbuvir/velpatasvir is a combination of two drugs in one tablet that is approved for the treatment of patients with chronic hepatitis C virus (HCV) infection. When patients with chronic HCV infection receive a liver transplant, the HCV infection usually recurs, and damages the transplanted liver. This study tested the effects of 12 weeks of sofosbuvir/velpatasvir treatment in patients who had HCV recurrence after a liver transplant. Three months following the end of treatment, 96% of patients were cured of HCV infection. Clinical trial number: NCT02781571.

Abstract

BACKGROUND & AIMS Sofosbuvir, an NS5B inhibitor, combined with velpatasvir, an NS5A inhibitor (SOF/VEL), produces high sustained virologic response rates 12 weeks after treatment (SVR12) in patients with genotype 1-6 HCV infection, and has no anticipated clinically relevant drug-drug interactions with immunosuppressants. This study evaluated the safety and efficacy of SOF/VEL in adults with recurrent chronic genotype 1-4 HCV infection after liver transplant. METHODS Patients received SOF/VEL 400/100 mg daily for 12 weeks. Patients could be treatment experienced or treatment naïve with no cirrhosis or with compensated cirrhosis. The primary endpoints were SVR12 and discontinuations due to adverse events. RESULTS A total of 79 patients were enrolled and treated in this study (37 [47%] had genotype 1, 3 [4%] genotype 2, 35 [44%] genotype 3, and 4 [5%] genotype 4 HCV). Of these, 81% were male, 82% were white, 18% had compensated cirrhosis, and 59% were treatment experienced. The most commonly used immunosuppressants were tacrolimus (71%), mycophenolic acid (24%), cyclosporine (14%), and azathioprine (11%). Median (range) time from liver transplantation was 7.5 (0.3, 23.9) years. The SVR12 rate was 96%. By genotype, SVR12 rates were 95% (genotype 1), 100% (genotype 2), 97% (genotype 3), and 100% (genotype 4). Two patients experienced virologic relapse: one with genotype 1a infection was non-cirrhotic and treatment naïve, and one with genotype 3 infection was non-cirrhotic and treatment experienced. One patient discontinued SOF/VEL due to hyperglycemia. No serious or severe adverse events were deemed SOF/VEL-related by the investigator, and no liver transplant rejection episodes or deaths occurred during the study period. CONCLUSIONS Treatment with SOF/VEL for 12 weeks was highly effective and well tolerated in genotype 1-4 HCV-infected liver transplant recipients with and without cirrhosis. LAY SUMMARY Sofosbuvir/velpatasvir is a combination of two drugs in one tablet that is approved for the treatment of patients with chronic hepatitis C virus (HCV) infection. When patients with chronic HCV infection receive a liver transplant, the HCV infection usually recurs, and damages the transplanted liver. This study tested the effects of 12 weeks of sofosbuvir/velpatasvir treatment in patients who had HCV recurrence after a liver transplant. Three months following the end of treatment, 96% of patients were cured of HCV infection. Clinical trial number: NCT02781571.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Hepatology
Language:English
Date:September 2018
Deposited On:06 Dec 2018 14:44
Last Modified:29 Jul 2020 08:17
Publisher:Elsevier
ISSN:0168-8278
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.jhep.2018.05.039
PubMed ID:29886154

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