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Observational Study
. 2017 Oct;66(4):1090-1101.
doi: 10.1002/hep.29258. Epub 2017 Sep 4.

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  1 , Vandana Khungar  2 , Elizabeth C Verna  3 , Josh Levitsky  4 , Robert S Brown Jr  5 , Mohamed A Hassan  6 , Mark S Sulkowski  7 , Jacqueline G O'Leary  8 , Farrukh Koraishy  9 , Joseph S Galati  10 , Alexander A Kuo  11 , Monika Vainorius  12 , Lucy Akushevich  12 , David R Nelson  13 , Michael W Fried  12 , Norah Terrault  1 , K Rajender Reddy  2
Affiliations
Observational Study

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 et al. Hepatology. 2017 Oct.

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).

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Conflict of interest statement

Conflict of Interest Disclosures:

The authors’ disclosure of conflicts of interest are detailed below:

EV discloses institutional grant funding from Salix. JL discloses institutional grant funding to Novartis, sponsored lectures from Gilead and Novartis, along with stockholder for Transplant Genomics Incorporated. RSB discloses institutional grant funding from Abbvie, Janssen, Gilead, Merck along with consultant work for Abbvie, Janssen, and Gilead. MSS discloses institutional grant funding from Abbvie, Gilead, Janssen, Merck and Tobira along with consulting for Abbvie, Gilead, Janssen, Merck, Cocrystal, Trek. JGO discloses institutional grant funding for Astellas, Novartis, Abbvie, Gilead, and Intercept along with speaker for Abbvie, Gilead, and Merck. JSG discloses grant funding from Gilead Science Merck and is a speaker for Gilead and Merck. AK discloses grant funding from Gilead. DRN discloses institutional grant funding from Abbvie, Gilead, BMS, Janssen, Merck, and GSK along with Stock from TargetPharmaSolutions. MWF discloses grant funding and consulting from Merck, Gilead, Bristol Myers Squibb, AbbVie. NAT discloses institutional grant funding from Gilead, AbbVie, Merck, Eisai and Biotest and has served as consultant for Merck, Achillion, Bristol-Myers Squibb and Janssen. KRR discloses institutional grant funding from Abbvie Merck, and Gilead. The remaining authors have no conflicts to declare.

Figures

Figure 1
Figure 1
CONSORT of Patients. AE, adverse event; DAC, daclatasvir; EOT, end of treatment; LDV, ledipasvir; MV, multivariable; PrOD, ombitasvir/paritaprevir/ritonavir/dasabuvir; RBV, ribavirin; SOF, sofosbuvir; SVR, sustained virologic response
Figure 2
Figure 2. Sustained Virologic Response (Per-Protocol population)
A. Liver Transplant Recipients B. Kidney Transplant Recipients C. Liver and Kidney Transplant Recipients In Per Protocol population, SVR12 rates with 95% confidence intervals among all, cirrhotic, non-cirrhotic, LDV/SOF ± RBV treated, PrOD ± RBV treated and DAC/SOF ± RBV liver transplant recipients (panel A), kidney transplant recipients (panel B) and dual liver kidney transplant recipients (panel C). DAC, daclatasvir; LDV, ledipasvir; LCL, lower confidence limit; PrOD, ombitasvir/paritaprevir/ritonavir + dasabuvir; RBV, ribavirin; SOF, sofosbuvir; SVR12, sustained virologic response at week 12; UCL, upper confidence limit
Figure 3
Figure 3. Predictors of Sustained Virologic Response in the overall population
Multivariable analysis of SVR12 among patients with per protocol data treated with LDV/SOF ± RBV including patients with and without solid organ transplant. Associations between every baseline covariate and SVR12 were estimated with logistic regression using Firth penalized maximum likelihood estimation of the effect of a covariate of interest with adjustment for age and sex. Covariates treated in this manner are annotated with *.
Figure 4
Figure 4. Predictors of Sustained Virologic Response among LT patients
Multivariable analysis of SVR12 among LT patients with per protocol data treated with LDV/SOF ± RBV. KT patients were excluded from the analysis. Associations between every baseline covariate and SVR12 were estimated with logistic regression using Firth penalized maximum likelihood estimation of the effect of a covariate of interest with adjustment for age and sex. Covariates treated in this manner are annotated with *.
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References

    1. Crespo G, Marino Z, Navasa MForns X. Viral hepatitis in liver transplantation. Gastroenterology. 2012;142:1373–1383.e1. - PubMed
    1. Perico N, Cattaneo D, Bikbov BRemuzzi G. Hepatitis C infection and chronic renal diseases. Clin J Am Soc Nephrol. 2009;4:207–20. - PubMed
    1. Roth D, Gaynor JJ, Reddy KR, Ciancio G, Sageshima J, Kupin W, et al. Effect of kidney transplantation on outcomes among patients with hepatitis C. J Am Soc Nephrol. 2011;22:1152–60. - PMC - PubMed
    1. Lopez-Medrano F, Fernandez-Ruiz M, Morales JM, San-Juan R, Cervera C, Carratala J, et al. Impact of hepatitis C virus infection on the risk of infectious complications after kidney transplantation: data from the RESITRA/REIPI cohort. Transplantation. 2011;92:543–9. - PubMed
    1. Özgür O, Boyacioĝlu S, Telatar HHaberal M. Recombinant α-interferon in renal allograft recipients with chronic hepatitis C. Nephrol Dial Transplantation. 1995;10:2104–2106. - PubMed

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