Hepatitis C virus and the kidney


Hepatitis C virus (HCV) infection is more prevalent and is associated with higher mortality in patients receiving dialysis and in kidney transplant recipients than in the general population. Kidney transplant recipients who are HCV-positive are also at higher risk of allograft and liver failure than are HCV-negative recipients. Moreover, HCV infection is associated with a higher incidence and faster progression of diabetes mellitus and chronic kidney disease (CKD), as well as a higher incidence of systemic (especially cardiovascular) complications. The finding that these complications of HCV infection are attenuated in patients who achieve a sustained virologic response (SVR) emphasizes the need to treat patients with CKD who are HCV-positive with oral antiviral therapies. Fortunately, the available evidence suggests that a SVR can be achieved in >95% of patients with late-stage CKD and in kidney transplant recipients. According to international guidelines, all patients with CKD and HCV infection should be considered for treatment with direct acting antivirals (DAAs), prioritizing those with symptomatic cryoglobulinaemic vasculitis, extensive liver fibrosis and stage 4–5 CKD. DAA treatment can be delayed until after transplantation in recipients whose waiting time is markedly reduced by accepting an HCV-positive organ. An emerging issue is the long-term renal safety of DAAs, which requires a re-appraisal. Overall, the elimination of HCV from patients with CKD now seems to be achievable, provided that DAA treatment is coupled with reinforced hygienic precautions to prevent reinfections in dialysis units.

Key points

  • Hepatitis C virus (HCV) infection is more frequent in patients with chronic kidney disease (CKD) than in the general population; it is associated with a high risk of hepatic and extra-hepatic complications, including rapid CKD progression.

  • Patients with CKD and HCV infection should be considered for treatment with direct acting antivirals (DAAs).

  • Current DAA regimens lead to a sustained virologic response (SVR) in over 95% of patients with severe CKD.

  • Achieving a SVR decreases the risk of both hepatic and extra-hepatic complications; understanding the long-term effects of DAAs on kidney function requires additional follow-up studies.

  • Use of HCV-positive organs in HCV-negative kidney transplant candidates could reduce the waiting time for transplantation; HCV infection should then be treated after kidney transplantation.

  • Coupling antiviral treatment with reinforced hygienic precautions to prevent reinfections, especially in haemodialysis units, has the potential to eliminate HCV infection from the nephrology field.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: HCV infection is a systemic disease.
Fig. 2: Mechanisms of kidney damage following HCV infection.
Fig. 3: The HCV replication cycle and sites of action of direct acting antivirals.
Fig. 4: History of antiviral therapies for HCV infection.
Fig. 5: Therapeutic options for treating hepatitis C virus infection.


  1. 1.

    Polaris Observatory HCV Collaborators. Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. Lancet Gastroenterol. Hepatol. 2, 161–176 (2017).

  2. 2.

    Stanaway, J. et al. The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013. Lancet 388, 1081–1088 (2016).

  3. 3.

    World Health Organization. Eliminate hepatitis (news release, Geneva). WHO http://www.who.int/news-room/detail/27-07-2017-eliminate-hepatitis-who (2017).

  4. 4.

    Trinchet, J.-C. et al. Complications and competing risks of death in compensated viral cirrhosis (ANRS CO12 CirVir prospective cohort). Hepatology 62, 737–750 (2015).

  5. 5.

    Pozzato, G. et al. Hepatitis C virus and non-Hodgkin’s lymphomas: meta-analysis of epidemiology data and therapy options. World J. Hepatol. 8, 107–116 (2016).

  6. 6.

    Vescovo, T. et al. Autophagy in HCV infection: keeping fat and inflammation at bay. Biomed. Res. Int. 2014, 265353 (2014).

  7. 7.

    Del Campo, J. et al. Role of inflammatory response in liver disease: therapeutic strategies. World J. Hepatol. 10, 1–7 (2018).

  8. 8.

    Muriel, P. Role of free radicals in liver diseases. Hepatol. Int. 3, 526–536 (2009).

  9. 9.

    García-Monzón, C. et al. Intrahepatic accumulation of nitrotyrosine in chronic viral hepatitis is associated with histological severity of liver disease. J. Hepatol. 32, 331–338 (2000).

  10. 10.

    Fukui, M., Kitagawa, Y., Nakamura, N. & Yoshikawa, T. Hepatitis C virus and atherosclerosis in patients with type 2 diabetes. JAMA 289, 1245–1246 (2003).

  11. 11.

    Adinolfi, L. E. et al. Chronic HCV infection is a risk of atherosclerosis. Role of HCV and HCV-related steatosis. Atherosclerosis 221, 496–502 (2012).

  12. 12.

    Mostafa, A. et al. Hepatitis C infection and clearance: impact on atherosclerosis and cardiometabolic risk factors. Gut 59, 1135–1340 (2010).

  13. 13.

    Petta, S., Macaluso, F. S. & Craxi, A. Cardiovascular diseases and HCV infection: a simple association or more? Gut 63, 369–375 (2014).

  14. 14.

    Pol, S., Vallet-Pichard, A. & Hermine, O. Extrahepatic cancers and chronic HCV infection. Nat. Rev. Gastroenterol. Hepatol. 15, 283–290 (2018).

  15. 15.

    Allison, R. D. et al. Increased incidence of cancer and cancer-related mortality among persons with chronic hepatitis C infection, 2006–2010. J. Hepatol. 63, 822–828 (2015).

  16. 16.

    Fiorino, S. et al. Possible association between hepatitis C virus and malignancies different from hepatocellular carcinoma: a systematic review. World J. Gastroenterol. 21, 12896–12953 (2015).

  17. 17.

    Mahale, P. et al. Hepatitis C virus infection and the risk of cancer among elderly US adults: a registry-based case-control study. Cancer 123, 1202–1211 (2017).

  18. 18.

    Mills, K. T. et al. A systematic analysis of worldwide population-based data on the global burden of chronic kidney disease in 2010. Kidney Int. 88, 950–957 (2015).

  19. 19.

    Li, L. et al. A within-patient analysis for time-varying risk factors of CKD progression. J. Am. Soc. Nephrol. 25, 606–613 (2014).

  20. 20.

    Fissell, R. B. et al. Patterns of hepatitis C prevalence and seroconversion in hemodialysis units from three continents: the DOPPS. Kidney Int. 65, 2335–2342 (2004).

  21. 21.

    Lee, M. H. et al. Chronic hepatitis C virus infection increases mortality from hepatic and extrahepatic diseases: a community-based long-term prospective study. J. Infect. Dis. 206, 469–477 (2012).

  22. 22.

    Park, H. et al. A meta-analytic assessment of the risk of chronic kidney disease in patients with chronic hepatitis C virus infection. J. Viral Hepat. 22, 897–905 (2015).

  23. 23.

    Tarantino, A. et al. Long-term predictors of survival in essential mixed cryoglobulinemic glomerulonephritis. Kidney Int. 47, 618–623 (1995).

  24. 24.

    Su, F. H. et al. Association of hepatitis C virus infection with risk of ESRD: a population-based study. Am. J. Kidney Dis. 60, 553–560 (2012).

  25. 25.

    Al-Rabadi, L. et al. Rationale for treatment of hepatitis C virus infection in end-stage renal disease patients who are not kidney transplant candidates. Hemodial. Int. 22, S45–S52 (2018).

  26. 26.

    Hsu, Y. C. et al. Association between antiviral treatment and extrahepatic outcomes in patients with hepatitis C virus infection. Gut 64, 495–503 (2015).

  27. 27.

    Fabrizi, F., Dixit, V. & Messa, P. Impact of hepatitis C on survival in dialysis patients: a link with cardiovascular mortality? J. Viral Hepat. 19, 601–607 (2012).

  28. 28.

    Pol, S. et al. Chronic hepatitis in kidney allograft recipients. Lancet 335, 878–880 (1990).

  29. 29.

    Mathurin, P. et al. Impact of hepatitis B and C virus on kidney transplantation outcome. Hepatology 29, 257–263 (1999).

  30. 30.

    Bruchfeld, A., Wilczek, H. & Elinder, C. G. Hepatitis C infection, time in renal-replacement therapy, and outcome after kidney transplantation. Transplantation 78, 745–750 (2004).

  31. 31.

    Scott, D. R. et al. Adverse impact of hepatitis C virus infection on renal replacement therapy and renal transplant patients in Australia and New Zealand. Transplantation 90, 1165–1171 (2010).

  32. 32.

    Fabrizi, F., Martin, P., Dixit, V., Bunnapradist, S. & Dulai, G. Hepatitis C virus antibody status and survival after renal transplantation: meta-analysis of observational studies. Am. J. Transplant. 5, 1452–1461 (2005).

  33. 33.

    AASLD–IDSA. HCV guidance: recommendations for testing, managing, and treating hepatitis C. HCV Guidelines http://www.hcvguidelines.org (2017).

  34. 34.

    European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2016. J. Hepatol. 66, 153–194 (2017).

  35. 35.

    Jadoul, M. et al. Executive summary of the 2018 KDIGO hepatitis C in CKD guideline: welcoming advances in evaluation and management. Kidney Int. 94, 663–673 (2018).

  36. 36.

    Jadoul, M. et al. Transmission routes of HCV infection in dialysis. Nephrol. Dial. Transplant. 11, 36–38 (1996).

  37. 37.

    Isnard-Bagnis, C. et al. Epidemiology update for HCV and HBV in ESRD in France (REIN registry). Liver Int. 37, 820–826 (2017).

  38. 38.

    Sauné, K. et al. Decreased prevalence and incidence of HCV markers in haemodialysis units: a multicentric French survey. Nephrol. Dial. Transplant. 26, 2309–2316 (2011).

  39. 39.

    Goodkin, D. A. & Bieber, B. International prevalence of hepatitis C positivity among hemodialysis patients awaiting transplantation. Kidney Int. 93, 1249 (2018).

  40. 40.

    Thursz, M. & Fontanet, A. HCV transmission in industrialized countries and resource-constrained areas. Nat. Rev. Gastroenterol. Hepatol. 11, 28–35 (2014).

  41. 41.

    Goodkin, D. A. et al. Mortality, hospitalization, and quality of life among patients with hepatitis C infection on hemodialysis. Clin. J. Am. Soc. Nephrol. 12, 287–297 (2017).

  42. 42.

    Baid-Agrawal, S. et al. Prevalence of occult hepatitis C infection in chronic hemodialysis and kidney transplant patients. J. Hepatol. 60, 928–933 (2014).

  43. 43.

    Fontaine, H. et al. Reassessment of prognostic impact of infection by hepatitis C and B virus in kidney allograft recipients [C-30]. Presented at the 75th Annual Meeting of the French Association for the Study of Liver in Lille, France (2–5 October 2013).

  44. 44.

    Boerekamp, A. et al. Declining hepatitis C virus (HCV) incidence in Dutch human immunodeficiency virus-positive men who have sex with men after unrestricted access to HCV therapy. Clin. Infect. Dis. 66, 1360–1365 (2018).

  45. 45.

    Ozkok, A. & Yildiz, A. Hepatitis C virus associated glomerulopathies. World J. Gastroenterol. 20, 7544–7554 (2014).

  46. 46.

    Zignego, A. L., Gianini, C. & Gragnani, L. HCV and lymphoproliferation. Clin. Dev. Immunol. 2012, 980–942 (2012).

  47. 47.

    Sethi, S. & Fervenza, F. C. Membranoproliferative glomerulonephritis-a new look at an old entity. N. Engl. J. Med. 366, 1119–1131 (2012).

  48. 48.

    Sabry, A. et al. HCV associated glomerulopathy in Egyptian patients: clinicopathological analysis. Virology 334, 10–16 (2005).

  49. 49.

    Sansonno, D. et al. Hepatitis C virus-related proteins in kidney tissue from hepatitis C virus-infected patients with cryoglobulinemic membranoproliferative glomerulonephritis. Hepatology 25, 1237–1244 (1997).

  50. 50.

    Negro, F. et al. Extrahepatic morbidity and mortality of chronic hepatitis C. Gastroenterology 149, 1345–1360 (2015).

  51. 51.

    Fabrizi, F. et al. Hepatitis C virus infection, mixed cryoglobulinemia, and kidney disease. Am. J. Kidney Dis. 61, 623–637 (2013).

  52. 52.

    Koutsoudakis, G. et al. The level of CD81 cell surface expression is a key determinant for productive entry of hepatitis C virus into host cells. J. Virol. 81, 588–598 (2007).

  53. 53.

    Rosa, D. et al. Activation of B lymphocytes via CD81, a pathogenic mechanism for hepatitis C virus-associated B lymphocytes disorders. Proc. Natl Acad. Sci. USA 102, 18544–18549 (2005).

  54. 54.

    Fletcher, N. F. et al. Hepatitis C virus infects the endothelial cells of the blood-brain barrier. Gastroenterology 142, 634–643 (2012).

  55. 55.

    Balasubramanian, A. et al. Structural proteins of hepatitis C virus induce interleukin 8 production and apoptosis in human endothelial cells. J. Gen. Virol. 86, 3291–3305 (2005).

  56. 56.

    Wörnle, M. et al. Novel role of toll-like receptor 3 in hepatitis C-associated glomerulonephritis. Am. J. Pathol. 168, 370–385 (2006).

  57. 57.

    Abou-Zeid, A. A. & El-Sayegh, H. K. Toll-like receptor 3 gene expression in Egyptian patients with glomerulonephritis and hepatitis C virus infection. Scan. J. Clin. Lab. Invest. 71, 456–461 (2011).

  58. 58.

    Hwang, J. C. et al. Impact of HCV infection on diabetes patients for the risk of end-stage renal failure. Medicine 95, e2431 (2016).

  59. 59.

    Kohli, H. S. et al. Treatment related acute renal failure in the elderly: a hospital-based prospective study. Nephrol. Dial. Transplant. 15, 212–217 (2000).

  60. 60.

    Naughton, C. A. Drug-induced nephrotoxicity. Am. Fam. Physician 78, 743–750 (2008).

  61. 61.

    Zignego, A. L. et al. Genome-wide association study of Hepatitis C virus- and cryoglobulin-related vasculitis. Genes Immun. 15, 500–505 (2014).

  62. 62.

    Cusato, J. et al. Pharmacogenetic analysis of hepatits C virus related mixed cryoglobulinemia. Pharmacogenomics 18, 607–611 (2017).

  63. 63.

    Wang, M., Liu, Q. & Liu, C. Correlation of CCR5 and NRLP3 gene polymorphisms with renal damage due to hepatits C virus-related cryoglobulinemia. Exp. Ther. Med. 16, 3055–3059 (2018).

  64. 64.

    Satapathy, S. K. et al. Higher prevalence of chronic kidney disease and shorter renal survival in patients with chronic hepatitis C virus infection. Hepatol. Int. 6, 369–378 (2012).

  65. 65.

    Park, H. et al. Chronic hepatitis C virus (HCV) increases the risk of chronic kidney disease (CKD) while effective HCV treatment decreases the incidence of CKD. Hepatology 67, 492–504 (2017).

  66. 66.

    Molnar, M. Z. et al. Association of hepatitis C viral infection with incidence and progression of chrnonic kidney disease in a large cohort of US veterans. Hepatology 61, 1495–1502 (2015).

  67. 67.

    Fontaine, H. et al. Cross-sectional study of chronic kidney disease prevalence in association with monoinfected patients hepatitis C virus in ANRS CO-22 Hepather cohort [abstract 798]. Hepatology 64, 393 (2016).

  68. 68.

    Cacoub, P., Desbois, A. C., Comarmond, C. & Saadoun, D. Impact of sustained virological response on the extrahepatic manifestations of chronic hepatitis C: a meta-analysis. Gut 67, 2025–2034 (2018).

  69. 69.

    Nahon, P. et al. Eradication of hepatitis C virus infection in patients with cirrhosis reduces risk of liver and non-liver complications. Gastroenterology 152, 142–156 (2017).

  70. 70.

    Ioannou, G. N., Green, P. K. & Berry, K. HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma. J. Hepatol. 68, 25–32 (2017).

  71. 71.

    Mallet, V. et al. Brief communication: the relationship of regression of cirrhosis to outcome in chronic hepatitis C. Ann. Intern. Med. 149, 399–403 (2008).

  72. 72.

    Buhler, S. & Bartenschlager, R. New targets for antiviral therapy of chronic hepatitis C. Liver Int. 32, 9–16 (2012).

  73. 73.

    Fontaine, H. et al. Recovery from chronic hepatitis C in long-term responders to ribavirin plus interferon alfa. Lancet 356, 41 (2000).

  74. 74.

    Pol, S. et al. The negative impact of HBV/HCV coinfection on cirrhosis and its consequences. Aliment. Pharmacol. Ther. 46, 1054–1060 (2017).

  75. 75.

    Pol, S. et al. Reversibility of hepatitis C virus-related cirrhosis. Hum. Pathol. 35, 107–112 (2004).

  76. 76.

    Hermine, O. et al. Regression of splenic lymphoma with lymphocytes after treatment of hepatitis C virus infection. N. Engl. J. Med. 347, 89–94 (2002).

  77. 77.

    Simmons, B., Saleem, J., Hill, A., Riley, R. D. & Cooke, G. S. Risk of late relapse or reinfection with hepatitis C virus after achieving a sustained virological response: a systematic review and meta-analysis. Clin. Infect. Dis. 15, 68394 (2016).

  78. 78.

    Söderholm, J. et al. Higher risk of renal disease in chronic hepatitis C patients: antiviral therapy survival benefit in patients on hemodialysis. J. Hepatol. 68, 904–911 (2018).

  79. 79.

    Bruchfeld, A. et al. Elbasvir plus grazoprevir in patients with hepatitis C virus infection and stage 4–5 chronic kidney disease: clinical, virological, and health-related quality-of-life outcomes from a phase 3, multicentre, randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol. Hepatol. 2, 585–594 (2017).

  80. 80.

    Cosconea, S. et al. Benefits associated with antiviral treatment in kidney allograft recipents with hepatitis B chronic infection. J. Hepatol. 57, 55–60 (2012).

  81. 81.

    Liang, T. J. & Ghany, M. G. Therapy of hepatitis C — back to the future. N. Engl. J. Med. 22, 2043–2047 (2014).

  82. 82.

    Pawlotsky, J. M., Feld, J. J., Zeuzem, S. & Hoofnagle, J. H. From non-A, non-B hepatitis to hepatitis C virus cure. Hepatology 62, S87–S99 (2015).

  83. 83.

    Roth, D. et al. Grazoprevir plus elbasvir in treatment-naïve and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4–5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet 386, 1537–1545 (2015).

  84. 84.

    Pockros, P. J. et al. Efficacy of direct-acting antiviral combination for patients with hepatitis C virus genotype 1 infection and severe renal impairment or end-stage renal disease. Gastroenterology 150, 1590–1598 (2016).

  85. 85.

    Carrat, F. et al. Clinical outcomes in patients with chronic hepatitis C following direct-acting antiviral therapy: a prospective cohort study. Lancet (in the press).

  86. 86.

    Mchutchison, J. G. et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatement of hepatitis C infection. N. Engl. J. Med. 361, 580–593 (2009).

  87. 87.

    Manns, M. P. et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 358, 958–965 (2001).

  88. 88.

    Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO clinical practice guidelines for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease. Kidney Int. 109, S1–S99 (2008).

  89. 89.

    Zeuzem, S. et al. Glecaprevir–pibrentasvir for 8 or 12 weeks in HCV genotype 1 or 3 infection. N. Engl. J. Med. 378, 354–369 (2018).

  90. 90.

    Jacobson, I. M. et al. Efficacy of 8 weeks of sofosbuvir, velpatasvir, and voxilaprevir in patients with chronic HCV infection: 2 phase 3 randomized trials. Gastroenterology 153, 113–122 (2017).

  91. 91.

    Kwo, P. et al. High SVR rates upon 8- or 12-week treatment with glecaprevir and pibrentasvir in patients with chronic HCV genotype 1–6 infection without cirrhosis. J. Hepatol. 67, 263–271 (2017).

  92. 92.

    Vogel, M. & Rockstroh, J. K. Hepatotoxicity and liver disease in the context of HIV therapy. Curr. Opin. HIV AIDS 2, 306–313 (2007).

  93. 93.

    Hezode, C. et al. Triple therapy in treatment-experienced patients with HCV-cirrhosis in a multicentre cohort of the French Early Access Programme (ANRS CO20-CUPIC) — NCT01514890. J. Hepatol. 59, 434–441 (2013).

  94. 94.

    Gane, E. et al. RUBY-II: efficacy and safety of a ribavirin-free ombitasvir/paritaprevir/ritonavir ± dasabuvir regimen in patients with severe renal impairment or end-stage renal disease and HCV genotype 1a or 4 infection. Presented at the 2016 AASLD Meeting in Boston, USA (11–15 Nov 2016).

  95. 95.

    Gane, E. et al. Glecaprevir and pibrentasvir in patients with HCV and severe renal impairment. N. Engl. J. Med. 377, 1448–1455 (2017).

  96. 96.

    Persico, M. et al. Efficacy and safety of glecaprevir/pibrentasvir in renally-impaired patients with chronic hepatitis C virus genotype 1–6 infection [abstract THU-363]. J. Hepatol. 68, S292 (2018).

  97. 97.

    Puoti, M. et al. High SVR12 with 8-week and 12-week glecaprevir/pibrentasvir therapy: an integrated analysis of HCV genotype 1–6 patients without cirrhosis. J. Hepatol. 69, 293–300 (2018).

  98. 98.

    Pol, S. et al. Safety and efficacy of glecaprevir/pibrentasvir in adults with chronic hepatitis C virus infection genotype 1–6 and chronic kidney disease: an integrated analysis [abstract SAT-273]. J. Hepatol. 66, S738 (2018).

  99. 99.

    Reddy, K. R. et al. Elbasvir/grazoprevir does not worsen renal function in patients with hepatitis C virus infection and pre-existing renal disease. Hepatol. Res. 47, 1340–1345 (2017).

  100. 100.

    Abergel, A. et al. High efficacy and safety of grazoprevir and elbasvir for 8 weeks in treatment-naive, non-severe fibrosis HCV GT1b-infected patients: interim results of the STREAGER study [abstract LBP-010]. J. Hepatol. 68, S110 (2018).

  101. 101.

    Asselah, T. et al. Efficacy and safety of 8 weeks of elbasvir/grazoprevir in HCV GT4-infected treatment-naive participants [abstract GS-006]. J. Hepatol. 68, S3–S4 (2018).

  102. 102.

    Sharma, S., Mukherjee, D., Nair, R. K., Datt, B. & Rao, A. Role of direct antiviral agents in treatment of chronic hepatitis C infection in renal transplant recipients. J. Transplant. 28, 7579689 (2018).

  103. 103.

    Colombo, M. et al. Treatment with ledipasvir-sofosbuvir for 12 or 24 weeks in kidney transplant recipients with chronic hepatitis C virus genotype 1 or 4 infection: a randomized trial. Ann. Intern. Med. 166, 109–117 (2017).

  104. 104.

    Reau, N. et al. Glecaprevir/pibrentasvir treatment in liver or kidney transplant patients with hepatitis C virus infection. Hepatology 68, 1298–1307 (2018).

  105. 105.

    Gane, E. J. et al. Safety, and anti-viral efficacy and pharmacokinetics (PK) of sofosbuvir (SOF) in patients with severe renal impairment [abstract 966]. Hepatology 60 (Suppl), 133A (2014).

  106. 106.

    Mehta, D. A. et al. Effect of hepatitis C treatment with ombitasvir/paritaprevir/R + dasabuvir on renal, cardiovascular and metabolic extrahepatic manifestations: a post-hoc analysis of phase 3 clinical trials. Infect. Dis. Ther. 6, 515–529 (2017).

  107. 107.

    Saxena, V. et al. 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 66, 1090–1101 (2017).

  108. 108.

    Maan, R. et al. The frequency of acute kidney injury in patients with chronic hepatitis C virus infection treated with sofosbuvir-based regimens. Aliment. Pharmacol. Ther. 46, 46–55 (2017).

  109. 109.

    Desnoyer, A. et al. Pharmacokinetics, safety and efficacy of a full dose sofosbuvir-based regimen given daily in hemodialysis patients with chronic hepatitis C. J. Hepatol. 65, 40–47 (2016).

  110. 110.

    Sise, M. E. et al. Effect of sofosbuvir-based hepatitis C virus therapy on kidney function in patients with CKD. Clin. J. Am. Soc. Nephrol. 12, 1615–1623 (2017).

  111. 111.

    Li, T. et al. Efficacy and safety of direct-acting antivirals-based antiviral therapies for hepatitis C virus patients with stage 4–5 chronic kidney disease: a meta-analysis. Liver Int. 37, 974–981 (2017).

  112. 112.

    Kamar, N. et al. Efficacy and safety of sofosbuvir-based antiviral therapy to treat hepatitis C virus infection after kidney transplantation. Am. J. Transplant. 16, 1474–1479 (2016).

  113. 113.

    Fernandez, I. et al. Efficacy and tolerability of interferon-free antiviral therapy in kidney transplant recipients with chronic hepatitis C. J. Hepatol. 66, 718–723 (2017).

  114. 114.

    Kumar, M., Nayak, S. L., Gupta, E., Kataria, A. & Sarin, S. K. Generic sofosbuvir based direct-acting antivirals in hepatitis C virus infected patients with chronic kidney disease. Liver Int. https://doi.org/10.1111/liv.13863 (2018).

  115. 115.

    Gilead Sciences Inc. Sovaldi [package insert]. Gilead.com http://www.gilead.com/~/media/Files/pdfs/medicines/liver-disease/sovaldi/sovaldi_pi.pdf (2017).

  116. 116.

    Bourliere, M. et al. Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection. N. Engl. J. Med. 376, 2134–2146 (2017).

  117. 117.

    Mallet, V. et al. Estimated glomerular filtration rate variations and direct acting antivirals treatment for chronic hepatitis C: a retrospective longitudinal study. J. Hepatol. 68, S22 (2018).

  118. 118.

    Strazzulla, A. et al. Evolution of glomerular filtration rates and neutrophil gelatinase-associated lipocalin during treatment with direct acting antivirals. Clin. Mol. Hepatol. 24, 151–162 (2018).

  119. 119.

    Ho, E. S., Lin, D. C., Mendel, D. B. & Cihlar, T. Cytotoxicity of antiviral nucleotides adefovir and cidofovir is induced by the expression of human renal organic anion transporter 1. J. Am. Soc. Nephrol. 11, 383–393 (2000).

  120. 120.

    Kohler, J. J. et al. Tenofovir renal proximal tubular toxicity is regulated by OAT1 and MRP4 transporters. Lab. Invest. 91, 852–858 (2011).

  121. 121.

    Tong, X. & Spradling, P. R. Increase in nonhepatic diagnoses among persons with hepatitis C hospitalized for any cause, United States, 2004–2011. J. Viral Hepat. 22, 906–913 (2015).

  122. 122.

    Butt, A. A., Wang, X. & Fried, L. F. HCV infection and the incidence of CKD. Am. J. Kidney Dis. 57, 396–402 (2011).

  123. 123.

    Lazarus, J. V. et al. Micro-elimination — a path to global elimination of hepatitis C. J. Hepatol. 67, 665–666 (2017).

  124. 124.

    Razavi, H. et al. Hepatitis C virus prevalence and level of intervention required to achieve the WHO targets for elimination in the European Union by 2030: a modelling study. Lancet Gastroenterol. Hepatol. 2, 325–336 (2017).

  125. 125.

    de Franchis, R. & Baveno, V.I.Faculty. Expanding consensus in portal hypertension: report of the Baveno VI consensus workshop: stratifying risk and individualizing care for portal hypertension. J. Hepatol. 63, 743–752 (2015).

  126. 126.

    Jadoul, M. & Horsmans, Y. Towards eradication of hepatitis C virus from dialysis units. Lancet 38, 1514–1515 (2015).

  127. 127.

    Jadoul, M. The prevention of hepatitis C virus transmission to hemodialysis patients and staff members. Hemodial. Int. 22, S104–S109 (2018).

  128. 128.

    O’Shaughnessy, M. M. et al. Re-infection following sustained virological response with a different hepatitis C virus genotype: implications for infection control policy. Clin. Kidney J. 5, 250–253 (2012).

  129. 129.

    US Department of Health & Human Services. Organ procurement and transplantation network. HRSA.gov https://optn.transplant.hrsa.gov/ (2018).

  130. 130.

    Haute Autorité de Santé. HAS homepage [French]. HAS https://www.has-sante.fr/ (2018).

  131. 131.

    Roth, D. & Ladino, M. Transplantation of kidneys from HCV-positive donors: how to best use a scarce resource. J. Am. Soc. Nephrol. 28, 3139–3141 (2017).

  132. 132.

    Gupta, G. et al. Long-term outcomes and transmission rates in hepatitis C virus-positive donor to hepatitis C virus-negative kidney transplant recipients: analysis of United States national data. Clin. Transplant. 31, e13055 (2017).

  133. 133.

    Kadatz, M., Klarenbach, S., Gill, J. & Gill, J. S. Cost-effectiveness of using kidneys from hepatitis C nucleic acid test positive donors for transplantation in hepatitis C negative recipients. Am. J. Transplant. 18, 2457–2464 (2018).

  134. 134.

    Goldberg, D. S., Abt, P. L. & Reese, P. P. Transplanting HCV-infected kidneys into uninfected recipients. N. Engl. J. Med. 377, 1105 (2017).

  135. 135.

    Reese, P. P. et al. Twelve-month outcomes after transplant of hepatitis C–infected kidneys into uninfected recipients. Ann. Intern. Med. 169, 273–281 (2018).

  136. 136.

    Durand, C. et al. EXPANDER-1: exploring renal transplants using hepatitis-C infected donors for HCV-negative recipients [abstract 2]. Am. J. Transplant. 17 (Suppl. 3), 207 (2017).

  137. 137.

    Parlati, L. et al. Evidence of HCV recovery after therapy of hepatitis C virus infection by direct acting antivirals. Clin. Res. Hepatol. Gastroenterol. https://doi.org/10.1016/j.clinre.2018.09.002 (2018).

  138. 138.

    Mehra, M. R. et al. The drug-intoxication epidemic and solid-organ transplantation. N. Engl. J. Med. 378, 1943–1945 (2018).

Download references

Reviewer information

Nature Reviews Nephrology thanks L. Rostaing, M. Sise and the other, anonymous reviewer(s) for their contribution to the peer review of this work.

Author information

All authors contributed equally to researching data for the article, discussions of the article’s content, writing the article, and review and/or editing of the manuscript before submission.

Correspondence to Stanislas Pol.

Ethics declarations

Competing interests

S.P. has acted as a speaker or board member for Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Gilead, Roche, MSD and Abbvie, and has received grants from Bristol-Myers Squibb, Gilead, Roche, Abbvie and MSD. M.J. has acted as a speaker for MSD and Abbvie, and as a Board Member for MSD. He has also received a grant from MSD. He co-chaired the 2018 update of the HCV and CKD KDIGO Guideline and is co-chair elect of KDIGO. L.P. declares no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


Variceal haemorrhage

Haematemesis or melena caused by esophageal or gastric varices rupture due to portal hypertension (associated with cirrhosis or non-cirrhotic portal hypertension).


Transudate abdominal effusion caused by the combination of portal hypertension and liver failure (hypoalbuminaemia) in cirrhosis.


The presence of proteins (mostly immunoglobulins) that precipitate and become insoluble at low temperatures (<37 °C).

Non-Hodgkin lymphoma

A group of blood cancers that develop in lymphocytes and include all types of lymphoma except Hodgkin lymphoma. Risk factors for developing non-Hodgkin lymphoma include hepatitis C virus infection, Epstein Barr virus infection, Helicobacter pylori infection and autoimmune disease.

Sustained virologic response

(SVR). Defined by undetectable levels of hepatitis C virus RNA in the serum 12 or 24 weeks after the end of antiviral treatment and corresponds to virologic cure.


A component of the innate immune system that promotes phagocytosis through opsonization of antigens and inflammation through the attraction of macrophages and neutrophils and the destruction of pathogenic cell membranes.

Fibrinoid necrosis

A form of necrosis that is characterized by the accumulation of a proteinaceous material in the matrix in response to an inflammatory stimulus. It is typical of immune vasculitis.


Proteins (mostly immunoglobulins) that precipitate and become insoluble at low temperatures (<37 °C)


Histological manifestations of glomerulonephritis that are caused by the proliferation of parietal epithelial cells lining the Bowman capsule in response to an inflammatory stimulus.

Tubular casts

The result of the intraluminal precipitation of Tamm–Horsfall mucoproteins, which are secreted by renal tubular cells. Cast formation is favoured by low flow, concentrated salts and low pH.

Enzyme immunoassay

(EIA). A biochemical test that measures the presence and/or concentration of a protein or enzyme in a solution (serum or urine) through the use of a specific antibody.

Ritonavir boost

Ritonavir is an efficient anti-HIV agent but is toxic at therapeutic doses. It is now used as a ‘booster’, to enhance the efficacy of protease inhibitors, thereby enabling the use of lower doses and reducing their putative toxicity.

Second-generation DAAs

Direct-acting antivirals (DAAs) available from 2013, including sofosbuvir, simeprevir, daclatasvir, ledipasvir, paritaprevir, ritonavir, ombitasvir, dasabuvir, elbasvir and grazoprevir.


Refers to direct-acting antivirals with established efficacy regardless of the hepatitis C virus genotype.

Decompensated cirrhosis

Refers to cirrhosis with ascites, variceal bleeding or hepatic encephalopathy.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Further reading