Direct Acting Antivirals in Hepatitis C-Infected Kidney Transplant Recipients: Associations with Long-term Graft Failure and Patient Mortality

Main Article Content

Michael R Goetsch
Ashutosh Tamhane
Edgar T Overton
Graham C Towns
Ricardo A Franco


Background: Direct-acting antiviral (DAA) therapy among hepatitis C virus (HCV)-infected kidney transplant recipients is associated with short-term improvement in protein/creatinine (P/C) ratios, but how HCV cure affects long-term graft outcomes remains unknown.

Methods: This is a retrospective follow-up study of 59 HCV-infected patients who underwent kidney transplant at the University of Alabama at Birmingham between 2007-2015 who were followed until the end of 2017. We examined the association of DAA-induced HCV cure with graft failure or death by survival analyses (Kaplan-Meier, Cox regression).

Redsults: Mean age was 55 years, 73% were African American, and 68% were male. Median baseline creatinine was 1.4 mg/dL, P/C ratio was 0.5, and estimated glomerular filtration rate (eGFR) was 59 mL/min. Of those who received DAA, 24 (83%) achieved cure. The remaining 5 DAA patients (17%) did not have documented evidence of sustained virologic response (SVR). Overall, 19 (32%) patients experienced graft failure or death; with lower incidence in treated patients than untreated (4 vs 15 events; 2.6 vs 10.3 per 100 person-years [cHR 0.19, 95% CI: 0.06–0.66]). When adjusted for age, sex, race, and proteinuria, the association remained strong and invariant across time-varying (aHR 0.30, 95% CI: 0.08–1.10), time-averaged (aHR 0.28, 95% CI: 0.07–1.07), and time-varying-cumulative (aHR 0.32, 95% CI: 0.08–1.21) proteinuria metrics.

Conclusions: DAAs therapy was associated with improved graft survival and reduced mortality. While not statistically significant, the association was strong, and these single-center findings warrant larger studies to demonstrate the benefits of HCV treatment in this population.


Download data is not yet available.

Article Details

Author Biography

Michael R Goetsch, Johns Hopkins Hospital

Department of Internal Medicine


1. Hofmeister MG, Rosenthal EM, Barker LK, Rosenberg ES, Barranco MA, Hall EW, Edlin BR, Mermin J, Ward JW, Ryerson AB. Estimating Prevalence of Hepatitis C Virus Infection in the United States, 2013-2016. Hepatology. 2019;69(3):1020-31. Epub 2018/11/07. doi: 10.1002/hep.30297. PubMed PMID: 30398671; PMCID: PMC6719781.

2. Global Hepatitis Report [Internet]. World Health Organization; 2017. Available from:;jsessionid=C6554B2D8BE2EB3A48DCBACFD0DCE138?sequence=1.

3. Viral Hepatitis Surveillance: United States, 2016 [Internet]. Centers for Disease Control and Prevention; 2016. Available from:

4. Spach DH. HCV Epidemiology in the United States [Internet]. University of Washington; 2019. Available from:

5. Chak E, Talal AH, Sherman KE, Schiff ER, Saab S. Hepatitis C virus infection in USA: an estimate of true prevalence. Liver Int. 2011;31(8):1090-101. Epub 2011/07/13. doi: 10.1111/j.1478-3231.2011.02494.x. PubMed PMID: 21745274.

6. Edlin BR, Eckhardt BJ, Shu MA, Holmberg SD, Swan T. Toward a more accurate estimate of the prevalence of hepatitis C in the United States. Hepatology. 2015;62(5):1353-63. Epub 2015/07/15. doi: 10.1002/hep.27978. PubMed PMID: 26171595; PMCID: PMC4751870.

7. Lee JJ, Lin MY, Chang JS, Hung CC, Chang JM, Chen HC, Yu ML, Hwang SJ. Hepatitis C virus infection increases risk of developing end-stage renal disease using competing risk analysis. PLoS One. 2014;9(6):e100790. Epub 2014/06/28. doi: 10.1371/journal.pone.0100790. PubMed PMID: 24971499; PMCID: PMC4074067.

8. Baid-Agrawal S, Farris AB, 3rd, Pascual M, Mauiyyedi S, Farrell ML, Tolkoff-Rubin N, Collins AB, Frei U, Colvin RB. Overlapping pathways to transplant glomerulopathy: chronic humoral rejection, hepatitis C infection, and thrombotic microangiopathy. Kidney Int. 2011;80(8):879-85. Epub 2011/06/24. doi: 10.1038/ki.2011.194. PubMed PMID: 21697808.

9. Cruzado JM, Carrera M, Torras J, Grinyo JM. Hepatitis C virus infection and de novo glomerular lesions in renal allografts. Am J Transplant. 2001;1(2):171-8. Epub 2002/07/09. PubMed PMID: 12099366.

10. Chute DF, Chung RT, Sise ME. Direct-acting antiviral therapy for hepatitis C virus infection in the kidney transplant recipient. Kidney Int. 2018;93(3):560-7. Epub 2018/01/13. doi: 10.1016/j.kint.2017.10.024. PubMed PMID: 29325996.

11. Shamseddin MK, Knoll GA. Posttransplantation proteinuria: an approach to diagnosis and management. Clin J Am Soc Nephrol. 2011;6(7):1786-93. Epub 2011/07/08. doi: 10.2215/CJN.01310211. PubMed PMID: 21734095.

12. Amer H, Cosio FG. Significance and management of proteinuria in kidney transplant recipients. J Am Soc Nephrol. 2009;20(12):2490-2. Epub 2009/10/13. doi: 10.1681/ASN.2008091005. PubMed PMID: 19820126.

13. Baid-Agrawal S, Pascual M, Moradpour D, Somasundaram R, Muche M. Hepatitis C virus infection and kidney transplantation in 2014: what’s new? Am J Transplant. 2014;14(10):2206-20. Epub 2014/08/06. doi: 10.1111/ajt.12835. PubMed PMID: 25091274.

14. Rostami Z, Nourbala MH, Alavian SM, Bieraghdar F, Jahani Y, Einollahi B. The impact of Hepatitis C virus infection on kidney transplantation outcomes: A systematic review of 18 observational studies: The impact of HCV on renal transplantation. Hepat Mon. 2011;11(4):247-54. Epub 2011/11/17. PubMed PMID: 22087151; PMCID: PMC3206701.

15. Morales JM, Fabrizi F. Hepatitis C and its impact on renal transplantation. Nat Rev Nephrol. 2015;11(3):172-82. Epub 2015/02/04. doi: 10.1038/nrneph.2015.5. PubMed PMID: 25643666.

16. Sawinski D, Bloom RD. Novel Hepatitis C Treatment and the Impact on Kidney Transplantation. Transplantation. 2015;99(12):2458-66. Epub 2015/07/28. doi: 10.1097/TP.0000000000000847. PubMed PMID: 26214816.

17. Goetsch MR, Tamhane A, Varshney M, Kapil A, Overton ET, Towns GC, Franco RA. Direct-Acting Antivirals in Kidney Transplant Patients: Successful Hepatitis C Treatment and Short-Term Reduction in Urinary Protein/Creatinine Ratios. Pathog Immun. 2017;2(3):366-75. Epub 2017/10/28. doi: 10.20411/pai.v2i3.211. PubMed PMID: 29075676; PMCID: PMC5654569.

18. Wong K, Cholankeril G, Gadiparthi C, Somasundar P, Busque S, Esquivel CO, Ahmed A. Improved Short-Term Survival in HCV Seropositive Kidney Transplant Recipients during the Daa Era in the United States. Hepatology. 2018;68:140A-A. PubMed PMID: WOS:000446020500225.

19. Barbour SJ, Cattran DC, Espino-Hernandez G, Hladunewich MA, Reich HN. Identifying the ideal metric of proteinuria as a predictor of renal outcome in idiopathic glomerulonephritis. Kidney Int. 2015;88(6):1392-401. Epub 2015/08/20. doi: 10.1038/ki.2015.241. PubMed PMID: 26287314.

20. Avasare RS, Radhakrishnan J. Proteinuria as a surrogate marker for renal outcome: are we there yet? Kidney Int. 2015;88(6):1228-30. Epub 2015/12/10. doi: 10.1038/ki.2015.301. PubMed PMID: 26649661.

21. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, Ckd EPI. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604-12. Epub 2009/05/06. doi: 10.7326/0003-4819-150-9-200905050-00006. PubMed PMID: 19414839; PMCID: PMC2763564.

22. VanderWeele TJ, Ding P. Sensitivity Analysis in Observational Research: Introducing the E-Value. Ann Intern Med. 2017;167(4):268-74. Epub 2017/07/12. doi: 10.7326/M16-2607. PubMed PMID: 28693043.

23. Sabbatini M, Capuano I, Camera S, Ferreri L, Buonanno P, Donnarumma L, Caporaso N, Morisco F. Eradication of HCV in Renal Transplant Recipients and Its Effects on Quality of Life. Biomed Res Int. 2018;2018:8953581. Epub 2018/09/25. doi: 10.1155/2018/8953581. PubMed PMID: 30246027; PMCID: PMC6136566.

24. Perico N, Cattaneo D, Bikbov B, Remuzzi G. Hepatitis C infection and chronic renal diseases. Clin J Am Soc Nephrol. 2009;4(1):207-20. Epub 2009/01/09. doi: 10.2215/CJN.03710708. PubMed PMID: 19129320.

25. Barsoum RS. Hepatitis C virus: from entry to renal injury--facts and potentials. Nephrol Dial Transplant. 2007;22(7):1840-8. Epub 2007/05/05. doi: 10.1093/ndt/gfm205. PubMed PMID: 17478492.

26. Barsoum RS, William EA, Khalil SS. Hepatitis C and kidney disease: A narrative review. J Adv Res. 2017;8(2):113-30. Epub 2017/02/06. doi: 10.1016/j.jare.2016.07.004. PubMed PMID: 28149647; PMCID: PMC5272932.

27. Adinolfi LE, Rinaldi L, Nevola R. Chronic hepatitis C, atherosclerosis and cardiovascular disease: What impact of direct-acting antiviral treatments? World J Gastroenterol. 2018;24(41):4617-21. Epub 2018/11/13. doi: 10.3748/wjg.v24.i41.4617. PubMed PMID: 30416309; PMCID: PMC6224469.

28. Saraiva GN, do Rosario NF, Medeiros T, Leite PEC, Lacerda GS, de Andrade TG, de Azeredo EL, Ancuta P, Almeida JR, Xavier AR, Silva AA. Restoring Inflammatory Mediator Balance after Sofosbuvir-Induced Viral Clearance in Patients with Chronic Hepatitis C. Mediators Inflamm. 2018;2018:8578051. Epub 2018/07/07. doi: 10.1155/2018/8578051. PubMed PMID: 29977152; PMCID: PMC5994301.

29. Mascia C, Vita S, Zuccala P, Marocco R, Tieghi T, Savinelli S, Rossi R, Iannetta M, Pozzetto I, Furlan C, Mengoni F, Mastroianni CM, Vullo V, Lichtner M. Changes in inflammatory biomarkers in HCV-infected patients undergoing direct acting antiviral-containing regimens with or without interferon. PLoS One. 2017;12(6):e0179400. Epub 2017/06/22. doi: 10.1371/journal.pone.0179400. PubMed PMID: 28636655; PMCID: PMC5499435.

30. Sise ME, Bloom AK, Wisocky J, Lin MV, Gustafson JL, Lundquist AL, Steele D, Thiim M, Williams WW, Hashemi N, Kim AY, Thadhani R, Chung RT. Treatment of hepatitis C virus-associated mixed cryoglobulinemia with direct-acting antiviral agents. Hepatology. 2016;63(2):408-17. Epub 2015/10/18. doi: 10.1002/hep.28297. PubMed PMID: 26474537; PMCID: PMC4718772.

31. Gragnani L, Visentini M, Fognani E, Urraro T, De Santis A, Petraccia L, Perez M, Ceccotti G, Colantuono S, Mitrevski M, Stasi C, Del Padre M, Monti M, Gianni E, Pulsoni A, Fiorilli M, Casato M, Zignego AL. Prospective study of guideline-tailored therapy with direct-acting antivirals for hepatitis C virus-associated mixed cryoglobulinemia. Hepatology. 2016;64(5):1473-82. Epub 2016/10/22. doi: 10.1002/hep.28753. PubMed PMID: 27483451.

32. Goldberg DS, Abt PL, Blumberg EA, Van Deerlin VM, Levine M, Reddy KR, Bloom RD, Nazarian SM, Sawinski D, Porrett P, Naji A, Hasz R, Suplee L, Trofe-Clark J, Sicilia A, McCauley M, Farooqi M, Gentile C, Smith J, Reese PP. Trial of Transplantation of HCV-Infected Kidneys into Uninfected Recipients. N Engl J Med. 2017;376(24):2394-5. Epub 2017/05/02. doi: 10.1056/NEJMc1705221. PubMed PMID: 28459186.

33. Omland LH, Krarup H, Jepsen P, Georgsen J, Harritshoj LH, Riisom K, Jacobsen SE, Schouenborg P, Christensen PB, Sorensen HT, Obel N, Study DC. Mortality in patients with chronic and cleared hepatitis C viral infection: a nationwide cohort study. J Hepatol. 2010;53(1):36-42. Epub 2010/04/20. doi: 10.1016/j.jhep.2010.01.033. PubMed PMID: 20400197.

34. Wasserstein RL, Schirm AL, Lazar NA. Moving to a World Beyond “p < 0.05”. The American Statistician. 2019;73(sup1):1-19. doi: 10.1080/00031305.2019.1583913.

Most read articles by the same author(s)