Safety and efficacy of current direct-acting antiviral regimens in kidney and liver transplant recipients with hepatitis C: Results from the HCV-TARGET study

Varun Saxena, Vandana Khungar, Elizabeth C. Verna, Josh Levitsky, Robert S. Brown, Mohamed A. Hassan, Mark S. Sulkowski, Jacqueline G. O'Leary, Farrukh Koraishy, Joseph S. Galati, Alexander A. Kuo, Monika Vainorius, Lucy Akushevich, David R. Nelson, Michael W. Fried, Norah Terrault, K. Rajender Reddy

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Abstract

Data outside of clinical trials with direct-acting antiviral regimens with or without ribavirin as treatment of chronic hepatitis C virus in solid organ transplant recipients are limited. Liver transplant (LT), kidney transplant (KT), and dual liver kidney (DLK) transplant recipients from the Hepatitis C Therapeutic Registry and Research Network database, a multicenter, longitudinal clinical care treatment cohort, treated with direct-acting antiviral regimens between January 1, 2014, and February 15, 2016, were included to assess safety and efficacy. Included were 443 posttransplant patients (KT = 60, LT = 347, DLK = 36); 42% had cirrhosis, and 54% had failed prior antiviral therapy. Most had genotype (GT) 1 (87% with 52% GT1a, 27% GT1b, and 8% GT1 no subtype) and were treated with sofosbuvir (SOF)/ledipasvir ± ribavirin (85%) followed by SOF + daclatasvir ± ribavirin (9%) and ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (6%). Rates of sustained virologic response (SVR) at 12 weeks were available on 412 patients, and 395 patients (95.9%) achieved SVR at 12 weeks: 96.6%, 94.5%, and 90.9% among LT, KT, and DLK transplant recipients, respectively. Ribavirin did not influence SVR rates and was more often used in those with higher BMI, higher estimated glomerular filtration rate and lower creatinine. Female gender, baseline albumin ≥3.5 g/dL, baseline total bilirubin ≤1.2 mg/dL, absence of cirrhosis, and hepatic decompensation predicted SVR at 12 weeks. Six episodes of acute rejection (n = 2 KT, 4 LT) occurred, during hepatitis C virus treatment in 4 and after cessation of treatment in 2. Conclusion: In a large prospective observational cohort study, direct-acting antiviral therapy with SOF/ledipasvir, ombitasvir/paritaprevir/ritonavir + dasabuvir, and SOF plus daclatasvir was efficacious and safe in LT, KT, and DLK transplant recipients; ribavirin did not influence SVR, and graft rejection was rare. (Hepatology 2017;66:1090-1101).

Original languageEnglish (US)
Pages (from-to)1090-1101
Number of pages12
JournalHepatology
Volume66
Issue number4
DOIs
StatePublished - Oct 1 2017

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Hepatitis C
Antiviral Agents
Transplants
Kidney
Safety
Ribavirin
Liver
Ritonavir
Hepacivirus
Transplant Recipients
Therapeutic Human Experimentation
Therapeutics
Withholding Treatment
Graft Rejection
Chronic Hepatitis C
Gastroenterology
Glomerular Filtration Rate
Bilirubin
Liver Cirrhosis
Observational Studies

ASJC Scopus subject areas

  • Hepatology

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Safety and efficacy of current direct-acting antiviral regimens in kidney and liver transplant recipients with hepatitis C : Results from the HCV-TARGET study. / Saxena, Varun; Khungar, Vandana; Verna, Elizabeth C.; Levitsky, Josh; Brown, Robert S.; Hassan, Mohamed A.; Sulkowski, Mark S.; O'Leary, Jacqueline G.; Koraishy, Farrukh; Galati, Joseph S.; Kuo, Alexander A.; Vainorius, Monika; Akushevich, Lucy; Nelson, David R.; Fried, Michael W.; Terrault, Norah; Reddy, K. Rajender.

In: Hepatology, Vol. 66, No. 4, 01.10.2017, p. 1090-1101.

Research output: Contribution to journalArticle

Saxena, V, Khungar, V, Verna, EC, Levitsky, J, Brown, RS, Hassan, MA, Sulkowski, MS, O'Leary, JG, Koraishy, F, Galati, JS, Kuo, AA, Vainorius, M, Akushevich, L, Nelson, DR, Fried, MW, Terrault, N & Reddy, KR 2017, 'Safety and efficacy of current direct-acting antiviral regimens in kidney and liver transplant recipients with hepatitis C: Results from the HCV-TARGET study', Hepatology, vol. 66, no. 4, pp. 1090-1101. https://doi.org/10.1002/hep.29258
Saxena, Varun ; Khungar, Vandana ; Verna, Elizabeth C. ; Levitsky, Josh ; Brown, Robert S. ; Hassan, Mohamed A. ; Sulkowski, Mark S. ; O'Leary, Jacqueline G. ; Koraishy, Farrukh ; Galati, Joseph S. ; Kuo, Alexander A. ; Vainorius, Monika ; Akushevich, Lucy ; Nelson, David R. ; Fried, Michael W. ; Terrault, Norah ; Reddy, K. Rajender. / Safety and efficacy of current direct-acting antiviral regimens in kidney and liver transplant recipients with hepatitis C : Results from the HCV-TARGET study. In: Hepatology. 2017 ; Vol. 66, No. 4. pp. 1090-1101.
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T1 - Safety and efficacy of current direct-acting antiviral regimens in kidney and liver transplant recipients with hepatitis C

T2 - Results from the HCV-TARGET study

AU - Saxena, Varun

AU - Khungar, Vandana

AU - Verna, Elizabeth C.

AU - Levitsky, Josh

AU - Brown, Robert S.

AU - Hassan, Mohamed A.

AU - Sulkowski, Mark S.

AU - O'Leary, Jacqueline G.

AU - Koraishy, Farrukh

AU - Galati, Joseph S.

AU - Kuo, Alexander A.

AU - Vainorius, Monika

AU - Akushevich, Lucy

AU - Nelson, David R.

AU - Fried, Michael W.

AU - Terrault, Norah

AU - Reddy, K. Rajender

PY - 2017/10/1

Y1 - 2017/10/1

N2 - Data outside of clinical trials with direct-acting antiviral regimens with or without ribavirin as treatment of chronic hepatitis C virus in solid organ transplant recipients are limited. Liver transplant (LT), kidney transplant (KT), and dual liver kidney (DLK) transplant recipients from the Hepatitis C Therapeutic Registry and Research Network database, a multicenter, longitudinal clinical care treatment cohort, treated with direct-acting antiviral regimens between January 1, 2014, and February 15, 2016, were included to assess safety and efficacy. Included were 443 posttransplant patients (KT = 60, LT = 347, DLK = 36); 42% had cirrhosis, and 54% had failed prior antiviral therapy. Most had genotype (GT) 1 (87% with 52% GT1a, 27% GT1b, and 8% GT1 no subtype) and were treated with sofosbuvir (SOF)/ledipasvir ± ribavirin (85%) followed by SOF + daclatasvir ± ribavirin (9%) and ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (6%). Rates of sustained virologic response (SVR) at 12 weeks were available on 412 patients, and 395 patients (95.9%) achieved SVR at 12 weeks: 96.6%, 94.5%, and 90.9% among LT, KT, and DLK transplant recipients, respectively. Ribavirin did not influence SVR rates and was more often used in those with higher BMI, higher estimated glomerular filtration rate and lower creatinine. Female gender, baseline albumin ≥3.5 g/dL, baseline total bilirubin ≤1.2 mg/dL, absence of cirrhosis, and hepatic decompensation predicted SVR at 12 weeks. Six episodes of acute rejection (n = 2 KT, 4 LT) occurred, during hepatitis C virus treatment in 4 and after cessation of treatment in 2. Conclusion: In a large prospective observational cohort study, direct-acting antiviral therapy with SOF/ledipasvir, ombitasvir/paritaprevir/ritonavir + dasabuvir, and SOF plus daclatasvir was efficacious and safe in LT, KT, and DLK transplant recipients; ribavirin did not influence SVR, and graft rejection was rare. (Hepatology 2017;66:1090-1101).

AB - Data outside of clinical trials with direct-acting antiviral regimens with or without ribavirin as treatment of chronic hepatitis C virus in solid organ transplant recipients are limited. Liver transplant (LT), kidney transplant (KT), and dual liver kidney (DLK) transplant recipients from the Hepatitis C Therapeutic Registry and Research Network database, a multicenter, longitudinal clinical care treatment cohort, treated with direct-acting antiviral regimens between January 1, 2014, and February 15, 2016, were included to assess safety and efficacy. Included were 443 posttransplant patients (KT = 60, LT = 347, DLK = 36); 42% had cirrhosis, and 54% had failed prior antiviral therapy. Most had genotype (GT) 1 (87% with 52% GT1a, 27% GT1b, and 8% GT1 no subtype) and were treated with sofosbuvir (SOF)/ledipasvir ± ribavirin (85%) followed by SOF + daclatasvir ± ribavirin (9%) and ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (6%). Rates of sustained virologic response (SVR) at 12 weeks were available on 412 patients, and 395 patients (95.9%) achieved SVR at 12 weeks: 96.6%, 94.5%, and 90.9% among LT, KT, and DLK transplant recipients, respectively. Ribavirin did not influence SVR rates and was more often used in those with higher BMI, higher estimated glomerular filtration rate and lower creatinine. Female gender, baseline albumin ≥3.5 g/dL, baseline total bilirubin ≤1.2 mg/dL, absence of cirrhosis, and hepatic decompensation predicted SVR at 12 weeks. Six episodes of acute rejection (n = 2 KT, 4 LT) occurred, during hepatitis C virus treatment in 4 and after cessation of treatment in 2. Conclusion: In a large prospective observational cohort study, direct-acting antiviral therapy with SOF/ledipasvir, ombitasvir/paritaprevir/ritonavir + dasabuvir, and SOF plus daclatasvir was efficacious and safe in LT, KT, and DLK transplant recipients; ribavirin did not influence SVR, and graft rejection was rare. (Hepatology 2017;66:1090-1101).

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