Hepatitis C Virus Infection and Renal Disorders
Main Article Content
Keywords
direct antiviral agents, extrahepatic disorders, hepatitis C virus, membranoproliferative glomerulonephritis, mixed cryoglobulinemia
Abstract
Hepatitis C virus (HCV) infection is frequently associated with extrahepatic disorders, among which renal diseases are frequent. This article highlights the most frequent HCV-associated renal disorders, the impact of HCV infection on chronic renal disease and renal transplantation, and the role of current direct-acting antiviral therapies. HCV is associated with membranoproliferative glomerulonephritis, acceleration of end-stage renal diseases in patients with glomerulopathies, and a higher risk of death in patients affected by chronic kidney disease. Before the introduction of direct-acting antiviral drugs as treatment modality, renal transplantation was a challenging clinical problem because the drugs available until 2011 obtained a poor sustained virologic response, had several side effects, and caused acute rejection when used after transplantation. The knowledge of the viral structure and its replication allowed the discovery of new classes of direct-acting antiviral drugs that revolutionized this scenario. These new drugs are comparatively more effective and safer. Accumulating evidence suggests that it is possible to cure HCV-related glomerulonephritis, and obtain a sustained virologic response in patients with renal failure, or on dialysis, before commencing transplantation. Finally, it became possible to transplant HCV-positive kidneys into HCV-positive or HCV-negative recipients.
References
2. Cacoub P, Poynard T, Ghillani P, Charlotte F, Olivi M, Piette JC, et al. Extrahepatic manifestations of chronic hepatitis C. MULTIVIRC Group. Multidepartment Virus C. Arthritis Rheum. 1999;42(10):2204–12. https://doi.org/10.1002/1529-0131(199910)42:10%3C2204::AID-ANR24%3E3.0.CO;2-D
3. Zignego AL, Ferri C, Pileri SA, Caini P, Bianchi FB, Italian Association of the Study of Liver Commission on Extrahepatic Manifestations of HCV infection. Extrahepatic manifestations of Hepatitis C Virus infection: A general overview and guidelines for a clinical approach. Dig Liver Dis. 2007;39(1):2–17. https://doi.org/10.1016/j.dld.2006.06.008
4. Terrier B, Cacoub P. Renal involvement in HCV-related vasculitis. Clin Res Hepatol Gastroenterol. 2013;37(4):334–9. https://doi.org/10.1016/j.clinre.2013.02.002
5. Sene D, Ghillani-Dalbin P, Thibault V, Guis L, Musset L, Duhaut P, et al. Longterm course of mixed cryoglobulinemia in patients infected with hepatitis C virus. J Rheumatol. 2004;31(11):2199–206.
6. Wigneswaran J, Van Wyck D, Pegues D, Gholam P, Nissenson AR. Hepatitis C virus infection in patients with end-stage renal disease. Hemodial Int. 2018;22(3):297–307. https://doi.org/10.1111/hdi.12672
7. Fissell RB, Bragg-Gresham JL, Woods JD, Jadoul M, Gillespie B, Hedderwick SA, et al. Patterns of hepatitis C prevalence and seroconversion in hemodialysis units from three continents: The DOPPS. Kidney Int. 2004;65(6):2335–42. https://doi.org/10.1111/j.1523-1755.2004.00649
8. Cacoub P, Renou C, Rosenthal E, Cohen P, Loury I, Loustaud-Ratti V, et al. Extrahepatic manifestations associated with hep-atitis C virus infection. A prospective multicenter study of 321 patients. The GERMIVIC. Groupe d'Etude et de Recherche en Medecine Interne et Maladies Infectieuses sur le Virus de l'Hep-atite C Medicine (Baltimore). 2000;79(1):47–56.
9. Huang JF, Chuang WL, Dai CY, Ho CK, Hwang SJ, Chen SC, et al. Viral hepatitis and proteinuria in an area endemic for hepatitis B and C infections: Another chain of link? J Intern Med. 2006;260(3):255–62. https://doi.org/10.1111/j.1365-2796.2006.01686.x
10. Tsui JI, Vittinghoff E, Shlipak MG, O'Hare AM. Relationship between hepatitis C and chronic kidney disease: Results from the Third National Health and Nutrition Examination Survey. J Am Soc Nephrol. 2006;17(4):1168–74. https://doi.org/10.1681/ASN.2005091006
11. Barsoum RS. Hepatitis C virus: From entry to renal injury--facts and potentials. Nephrol Dial Transplant. 2007;22(7):1840–8. https://doi.org/10.1093/ndt/gfm205
12. Rodríguez-Iñigo E, Casqueiro M, Bartolomé J, Barat A, Caramelo C, Ortiz A, et al. Hepatitis C virus RNA in kidney biopsies from infected patients with renal diseases. J Viral Hepat. 2000;7(1):23–9. https://doi.org/10.1046/j.1365-2893.2000.00194.x
13. Sansonno D, Gesualdo L, Manno C, Schena FP, Dammacco F. Hepatitis C virus-related proteins in kidney tissue from hepatitis C virus-infected patients with cryoglobulinemic membranoproliferative glomerulonephritis. Hepatology. 1997;25(5):1237–44. https://doi.org/10.1002/hep.510250529
14. Akira S, Takeda K, KaishoT. Toll-like receptors: Critical proteins linking innate and acquired immunity. Nat Immunol. 2001;2(8):675–80. https://doi.org/10.1038/90609
15. Schlipkoter U, Roggendorf M, Ernst G, Rasshofer R, Deinhardt F, Weise A, et al. Hepatitis C virus antibodies in hemodialysis patients. Lancet 1990;335 (8702):1409–10. https://doi.org/10.1016/0140-6736(90)91296-M
16. Forns X, Fernández-Llama P, Pons M, Costa J, Ampurdanés S, López-Labrador FX, et al. Incidence and risk factors of hepatitis C virus infection in a haemodialysis unit. Nephrol Dial Transplant. 1997;12(4):736–40. https://doi.org/10.1093/ndt/12.4.736
17. Knudsen F, Wantzin P, Rasmussen K, Ladefoged SD, Løkkegaard N, Rasmussen LS, et al. Hepatitis C in dialysis patients: Relationship to blood transfusions, dialysis and liver disease. Kidney Int. 1993;43(6):1353–6. https://doi.org/10.1038/ki.1993.190
18. Butt AA, Wang X, Fried LF. HCV infection and the incidence of CKD. Am J Kidney Dis. 2011;57(3):396–402. https://doi.org/10.1053/j.ajkd.2010.09.023
19. Dalrymple LS, Koepsell T, Sampson J, Louie T, Dominitz JA, Young B, et al. Hepatitis C virus infection and the prevalence of renal insufficiency. Clin J Am Soc Nephrol. 2007;2(4):715–21. https://doi.org/10.2215/CJN.00470107
20. Li M, Wang P, Yang C, Jiang W, Wei X, Mu X, et al. A systematic review and meta-analysis: Does hepatitis C virus infection predispose to the development of chronic kidney disease? Oncotarget. 2017;8(6):10692–702. https://doi.org/10.18632/oncotarget.12896
21. Fabrizi F, Dixit V, Messa P. Impact of hepatitis C on survival in dialysis patients: A link with cardiovascular mortality? J Viral Hepat. 2012;19(9):601–7.
22. Goodkin DA, Bragg-Gresham JL, Koenig KG, Wolfe RA, Akiba T, Andreucci VE, et al. Association of comorbid conditions and mortality in hemodialysis patients in Europe, Japan, and the United States: The Dialysis Outcomes and Practice Patterns Study (DOPPS). J Am Soc Nephrol. 2003;14(12):3270–7. https://doi.org/10.1111/j.1365-2893.2012.01633.x
23. Lee MH, Yang HI, Lu SN, Jen CL, You SL, Wang LY, et al. Chronic hepatitis C virus infection increases mortality from hepatic and extrahepatic diseases: A community-based long-term prospective study. J Infect Dis. 2012;206(4):469–77. https://doi.org/10.1111/j.1365-2893.2012.01633.x
24. Lai TS, Lee MH, Yang HI, You SL, Lu SN, Wang LY, et al. Hepatitis C viral load, genotype, and increased risk of developing end-stage renal disease: REVEAL-HCV study. Hepatology. 2017;66(3):784–93. https://doi.org/10.1002/hep.29192
25. Lai TS, Lee MH, Yang HI, You SL, Lu SN, Wang LY, et al. High hepatitis C viral load and genotype 2 are strong predictors of chronic kidney disease. Kidney Int. 2017;92(3):703–9. https://doi.org/10.1016/j.kint.2017.03.021
26. Kalantar-Zadeh K, Ikizler TA, Block G, Avram MM, Kopple JD. Malnutrition-inflammation complex syndrome in dialysis patients: Causes and consequences. Am J Kidney Dis. 2003;42(5):864–81. https://doi.org/10.1016/j.ajkd.2003.07.016
27. Oyake N, Shimada T, Murakami Y, Ishibashi Y, Satoh H, Suzuki K, et al. Hepatitis C virus infection as a risk factor for increased aortic stiffness and cardiovascular events in dialysis patients. J Nephrol. 2008;21(3):345–53.
28. Roccatello D, Fornasieri A, Giachino O, Rossi D, Beltrame A, Banfi G, et al. Multicenter study on hepatitis C virus-related cryoglobulinemic glomerulonephritis. Am J Kidney Dis. 2007; 49(1):69–82. https://doi.org/10.1053/j.ajkd.2006.09.015
29. Ozkok A, Yildiz A. Hepatitis C virus-associated glomerulopathies. World J Gastroenterol. 2014;20(24):7544–54. https://doi.org/10.3748/wjg.v20.i24.7544
30. Fabrizi F, Plaisier E, Saadoun D, Martin P, Messa P, Cacoub P. Hepatitis C virus infection, mixed cryoglobulinemia, and kidney disease. Am J Kidney Dis. 2013;61(4):623–37. https://doi.org/10.1053/j.ajkd.2012.08.040
31. Ferri C, Giuggioli D, Colaci M. Renal Manifestations of Hepatitis C Virus. Clin Liver Dis. 2017;21(3):487–97. https://doi.org/10.1016/j.cld.2017.03.005
32. Castillo I, Martinez-Ara J, Olea T, Bartolomé J, Madero R, Hernández E, et al. High prevalence of occult hepatitis C virus infection in patients with primary and secondary glomerular nephropathies. Kidney Int. 2014;86(3):619–24. https://doi.org/10.1038/ki.2014.68
33. Fabrizi F, Messa P, Martin P. Novel evidence on hepatitis C virus-associated glomerular disease. Kidney Int. 2014;86(3): 466–9. https://doi.org/10.1038/ki.2014.181
34. Cao Y, Zhang Y, Wang S, Zou W. Detection of the hepatitis C virus antigen in kidney tissue from infected patients with various glomerulonephritis. Nephrol Dial Transplant. 2009;24(9):2745–51. https://doi.org/10.1093/ndt/gfp167
35. Ragab G, Hussein MA. Vasculitic syndromes in hepatitis C virus: A review. J Adv Res. 2017;8(2):99–111. https://doi.org/10.1016/j.jare.2016.11.002
36. Rosa D, Saletti G, De Gregorio E, Zorat F, Comar C, D'OroU, et al. Activation of naïve B lymphocytes via CD81, a pathogenetic mechanism for hepatitis C virus-associated B lymphocyte disorders. Proc Natl Acad Sci USA. 2005;102(51):18544–9. https://doi.org/10.1073/pnas.0509402102
37. Schifferli JA, French LE, Tissot JD. Hepatitis C virus infection, cryoglobulinemia, and glomerulonephritis. Adv Nephrol Necker Hosp. 1995;24:107–29.
38. Misiani R, Bellavita P, Fenili D, Borelli G, Marchesi D, Massazza M, et al. Hepatitis C virus infection in patients with essential mixed cryoglobulinemia. Ann Intern Med. 1992;117(7):573–7. https://doi.org/10.7326/0003-4819-117-7-573
39. Rollino C, Roccatello D, Giachino O, Basolo B, Piccoli G. Hepatitis C virus infection and membranous glomerulonephritis. Nephron. 1991;59(2):319–20. https://doi.org/10.1159/000186573
40. Yamabe H, Johnson RJ, Gretch DR, Fukushi K, Osawa H, Miyata M, et al. Hepatitis C virus infection and membranoproliferative glomerulonephritis in Japan. J Am Soc Nephrol. 1995;6(2):220–3.
41. Horikoshi S, Okada T, Shirato I, Inokuchi S, Ohmuro H, Tomino Y, et al. Diffuse proliferative glomerulonephritis with hepatitis C virus-like particles in paramesangial dense deposits in a patient with chronic hepatitis C virus hepatitis. Nephron. 1993;64(3):462–4. https://doi.org/10.1159/000187372
42. Ji F, Li Z, Ge H, Deng H. Successful interferon-? treatment in a patient with IgA nephropathy associated with hepatitis C virus infection. Intern Med. 2010;49(22):2531–2. https://doi.org/10.2169/internalmedicine.49.4365
43. Gonzalo A, Navarro J, Bárcena R, Quereda C, Ortuño J. IgA nephropathy associated with hepatitis C virus infection. Nephron. 1995;69(3):354. https://doi.org/10.1159/000188494
44. Dey AK, Bhattacharya A, Majumdar A. Hepatitis C as a potential cause of IgA nephropathy. Indian J Nephrol. 2013;23(2):143–5. https://doi.org/10.4103/0971-4065.109443
45. Sperati CJ. Stabilization of hepatitis C associated collapsing focal segmental glomerulosclerosis with interferon alpha-2a and ribavirin. Clin Nephrol. 2013;80(3):231–4. https://doi.org/10.5414/CN107337
46. Shah HH, Patel C. Long-term response to peginterferon in hepatitis C virus-associated nephrotic syndrome from focal segmental glomerulosclerosis. Ren Fail. 2013;35(8):1182–5. https://doi.org/10.3109/0886022X.2013.815568
47. Markowitz GS, Cheng JT, Colvin RB, Trebbin WM, D'Agati VD. Hepatitis C viral infection is associated with fibrillary glomerulonephritis and immunotactoid glomerulopathy. J Am Soc Nephrol. 1998;9(12):2244–52.
48. Coroneos E, Truong L, Olivero J. Fibrillary glomerulonephritis associated with hepatitis C viral infection. Am J Kidney Dis. 1997;29(1):132–5. https://doi.org/10.1016/S0272-6386(97)90020-2
49. Guerra G, Narayan G, Rennke HG, Jaber BL. Crescentic fibrillary glomerulonephritis associated with hepatitis C viral infection. Clin Nephrol. 2003;60(5):364–8. https://doi.org/10.5414/CNP60364
50. Johnson RJ, Willson R, Yamabe H, Couser W, Alpers CE, Wener MH, et al. Renal manifestations of hepatitis C virus infection. Kidney Int. 1994;46(5):1255–63. https://doi.org/10.1038/ki.1994.393
51. Kasuno K, Ono T, Matsumori A, Nogaki F, Kusano H, Watanabe H, et al. Hepatitis C virus-associated tubulointerstitial injury. Am J Kidney Dis. 2003;41(4):767–75. https://doi.org/10.1016/S0272-6386(03)00024-6
52. Latt N, Alachkar N, Gurakar A. Hepatitis C virus and its renal manifestations: A review and update. Gastroenterol Hepatol (NY). 2012;8(7):434–45.
53. Barsoum RS, William EA, Khalil SS. Hepatitis C and kidney disease: A narrative review. J Adv Res. 2017;8(2):113–130. https://doi.org/10.1016/j.jare.2016.07.004
54. Knoll GA, Tankersley MR, Lee JY, Julian BA, Curtis JJ. The impact of renal transplantation on survival in hepatitis C-positive end-stage renal disease patients. Am J Kidney Dis. 1997;29(4):608–14. https://doi.org/10.1016/S0272-6386(97)90345-0
55. Pereira BJ, Natov SN, Bouthot BA, Murthy BV, Ruthazer R, Schmid CH, et al. Effects of hepatitis C infection and renal transplantation on survival in end-stage renal disease. The New England Organ Bank Hepatitis C Study Group. Kidney Int. 1998;53(5):1374–81. https://doi.org/10.1046/j.1523-1755.1998.00883.x
56. Bloom RD, Sayer G, Fa K, Constantinescu S, Abt P, Reddy KR. Outcome of hepatitis C virus-infected kidney transplant candidates who remain on the waiting list. Am J Transplant. 2005;5(1):139–44. https://doi.org/10.1046/j.1523-1755.1998.00883.x
57. Martin P, Fabrizi F. Hepatitis C virus and kidney disease. J Hepatol. 2008;49(4):613–24. https://doi.org/10.1016/j.jhep.2008.%3C200B%3E06.003
58. Cosio FG, Sedmak DD, Henry ML, Al Haddad C, Falkenhain ME, Elkhammas EA, et al. The high prevalence of severe early posttransplant renal allograft pathology in hepatitis C positive recipients. Transplantation. 1996;62(8):1054–9. https://doi.org/10.1097/00007890-199610270-00004
59. Fabrizi F, Martin P, Dixit V, Messa P. Meta-analysis of observational studies: Hepatitis C and survival after renal transplant. J Viral Hepat. 2014;21(5):314–24. https://doi.org/10.1111/jvh.12148
60. Singh N, Neidlinger N, Djamali A, Leverson G, Voss B, Sollinger HW, et al. The impact of hepatitis C virus donor and recipient status on long-term kidney transplant outcomes: University of Wisconsin experience. Clin Transplant. 2012;26(5):684–93. https://doi.org/10.1111/j.1399-0012.2011.01583.x
61. López-Medrano F, Fernández-Ruiz M, Morales JM, San-Juan R, Cervera C, Carratalá J, et al. Spanish Network for the Research of Infection in Transplantation/Network of Research in Infectious Diseases (RESITRA/REIPI) Study Group. Impact of hepatitis C virus infection on the risk of infectious complications after kidney transplantation: Data from the RESITRA/REIPI cohort. Transplantation. 2011;92(5):543–9. https://doi.org/10.1097/TP.0b013e318225dbae
62. Fabrizi F, Martin P, Dixit V, Bunnapradist S, Kanwal F, Dulai G. Post-transplant diabetes mellitus and HCV seropositive status after renal transplantation: Meta-analysis of clinical studies. Am J Transplant. 2005;5(10):2433–40. https://doi.org/10.1111/j.1600-6143.2005.01040.x
63. Demirci MS, Toz H, Yilmaz F, Ertilav M, Asci G, Ozkahya M, et al. Risk factors and consequences of post-transplant diabetes mellitus. Clin Transplant. 2010;24(5): E170–7. https://doi.org/10.1111/j.1399-0012.2010.01247.x
64. Masini M, Campani D, Boggi U, Menicagli M, Funel N, Pollera M, et al. Hepatitis C virus infection and human pancreatic beta-cell dysfunction. Diabetes Care. 2005;28(4):940–1. https://doi.org/10.2337/diacare.28.4.940
65. Burra P, Buda A, Livi U, Rigotti P, Zanus G, Calabrese F, et al. Occurrence of post-transplant lymphoproliferative disorders among over thousand adult recipients: Any role for hepatitis C infection? Eur J Gastroenterol Hepatol. 2006;18(10):1065–70. https://doi.org/10.1097/01.meg.0000231752.50587.ae
66. Brunkhorst R, Kliem V, Koch KM. Recurrence of membranoproliferative glomerulonephritis after renal transplantation in a patient with chronic hepatitis C. Nephron. 1996;72(3):465–7. https://doi.org/10.1159/000188914
67. McKay DB, Milford EL, Sayegh M. Clinical aspects of renal transplantation. In: Brenner BM, Rector FC editors. The kidney. PA: W.B. Saunders Company;1996, 2625–8.
68. Cruzado JM, Carrera M, Torras J, Grinyó JM. Hepatitis C virus infection and de novo glomerular lesions in renal allografts. Am J Transplant. 2001;1(2):171–8. https://doi.org/10.1034/j.1600-6143.2001.10212.x
69. Ponticelli C, Moroni G, Glassock RJ. De novo glomerular diseases after renal transplantation. Clin J Am Soc Nephrol. 2014;9(8):1479–87. https://doi.org/10.2215/CJN.12571213
70. Murphy DG, Sablon E, Chamberland J, Fournier E, Dandavino R, Tremblay CL. Hepatitis C virus genotype 7, a new genotype originating from central Africa. J Clin Microbiol. 2015;53(3):967–72. https://doi.org/10.1128/JCM.02831-14
71. Wéclawiack H, Kamar N, Mehrenberger M, Guilbeau-Frugier C, Modesto A, Izopet J, et al. Alpha-interferon therapy for chronic hepatitis C may induce acute allograft rejection in kidney transplant patients with failed allografts. Nephrol Dial Transplant. 2008;23(3):1043–7. https://doi.org/10.1093/ndt/gfm678
72. Tang S, Cheng IK, Leung VK, Kuok UI, Tang AW, Wing Ho Y, et al. Successful treatment of hepatitis C after kidney transplantation with combined interferon alpha-2b and ribavirin. J Hepatol. 2003;39(5):875–8. https://doi.org/10.1016/S0168-8278(03)00358-1
73. Fabrizi F, Penatti A, Messa P, Martin P. Treatment of hepatitis C after kidney transplant: A pooled analysis of observational studies. J Med Virol. 2014;86(6):933–40. https://doi.org/10.1002/jmv.23919
74. AASLD/IDSA HCV Guidance Panel. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;62(3):932–54. https://doi.org/10.1002/hep.27950
75. Saxena V, Koraishy FM, Sise ME, Lim JK, Schmidt M, Chung RT, et al. HCV-TARGET. Safety and efficacy of sofosbuvir-containing regimens in hepatitis C-infected patients with impaired renal function. Liver Int. 2016;36(6):807–16. https://doi.org/10.1111/liv.13102
76. Pockros PJ, Reddy KR, Mantry PS, Cohen E, Bennett M, Sulkowski MS, et al. Safety of ombitasvir/paritaprevir/ritonavir plus dasabuvir for treating HCV C1 infection in patients with severe renal impairment or end stage renal disease: The RUBY-1 sudy. J Hepatol. 2015;62:S257. https://doi.org/10.1016/S0168-8278(15)30147-1
77. Taneja S, Duseja A, De A, Kumar V, Ramachandran R, Sharma A, et al. Successful treatment of chronic hepatitis C infection with directly acting antivirals in renal transplant recipients. Nephrology (Carlton). 2018;23(9):876–82. https://doi.org/10.1111/nep.13109
78. Dammacco F, Tucci FA, Lauletta G, Gatti P, De Re V, Conteduca V, et al. Pegylated interferon-alpha, ribavirin, and rituximab combined therapy of hepatitis C virus-related mixed cryoglobulinemia: A long-term study. Blood. 2010 Jul;116(3):343–53. https://doi.org/10.1182/blood-2009-10-245878
79. Saadoun D, RescheRigon M, Sene D, Terrier B, Karras A, PerardL, et al. Rituximab plus Peg-interferon-alpha/ribavirin compared with Peg-interferon-alpha/ribavirin in hepatitis C-related mixed cryoglobulinemia. Blood. 2010 Jul;116(3):326–34. https://doi.org/10.1182/blood-2009-10-248518
80. Roccatello D, Sciascia S, Rossi D, Solfietti L, Fenoglio R, Menegatti E, et al. The challenge of treating hepatitis C virus-associated cryoglobulinemic vasculitis in the era of anti-CD20 monoclonal antibodies and direct antiviral agents. Oncotarget. 2017;8(25):41764–77. https://doi.org/10.18632/oncotarget.16986
81. Saadoun D, Thibault V, Si Ahmed SN, Alric L, Mallet M, GuillaudC, et al. Sofosbuvir plus ribavirin for hepatitis C virus-associated cryoglobulinaemia vasculitis: VASCUVALDIC study. Ann Rheum Dis. 2016;75(10):1777–82. https://doi.org/10.1136/annrheumdis-2015-208339
82. Saadoun D, Pol S, Ferfar Y, Alric L, Hezode C, Si Ahmed SN, et al. Efficacy and safety of Sofosbuvir Plus Daclatasvir for Treatment of HCV-Associated Cryoglobulinemia Vasculitis. Gastroenterology. 2017;153(1):49–52. https://doi.org/10.1053/j.gastro.2017.03.006
83. Gragnani L, Piluso A, Urraro T, Fabbrizzi A, Fognani E, Petraccia L, et al. Virological and clinical response to interferon-Free regimens in patients with HCV-Related Mixed Cryoglobulinemia: Preliminary results of a prospective pilot study. Curr Drug Targets. 2017;18(7):772–85. https://doi.org/10.2174/1389450117666160208145432
84. Emery JS, Kuczynski M, La D, Almarzooqi S, Kowgier M, Shah H, et al. Efficacy and safety of direct acting antivirals for the treatment of mixed Cryoglobulinemia. Am J Gastroenterol. 2017;112(8):1298–308. https://doi.org/10.1038/ajg.2017.49
85. Urraro T, Gragnani L, Piluso A, Fabbrizzi A, Monti M, Fognani E, et al. Combined treatment with antiviral therapy and rituximab in patients with mixed cryoglobulinemia: Review of the literature and report of a case using direct antiviral agents-based antihepatitis C virus therapy. Case Reports Immunol. 2015;2015:816424. https://doi.org/10.1155/2015/816424
86. KDIGO. Clinical Practice Guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease. Kidney Int Suppl. 2018;8(3):91–165. https://doi.org/10.1016/S2157-1716(18)30010-8
87. Ridruejo E, Mendizabal M, Silva MO. Rationale for treating hepatitis C virus infection in patients with mild to moderate chronic kidney disease. Hemodial Int. 2018;22 Suppl 1:S97–S103. https://doi.org/10.1111/hdi.12651
88. Fabrizi F, Messa P, Martin P. The unraveled link between chronic kidney disease and hepatitis C infection. New J Sci. 2014;2014:180203. https://doi.org/10.1155/2014/180203
89. Molnar MZ, Alhourani HM, Wall BM, Lu JL, Streja E, Kalantar-Zadeh K, et al. Association of hepatitis C viral infection with incidence and progression of chronic kidney disease in a large cohort of US veterans. Hepatology. 2015;61(5):1495–502. https://doi.org/10.1002/hep.27664
90. Liangpunsakul S, Chalasani N. Relationship between hepatitis C and microalbuminuria: Results from the NHANES III. Kidney Int. 2005;67(1):285–90. https://doi.org/10.1111/j.1523-1755.2005.00080.x
91. Swain MG, Lai MY, Shiffman ML, Cooksley WG, Zeuzem S, Dieterich DT, et al. A sustained virologic response is durable in patients with chronic hepatitis C treated with peginterferon alfa-2a and ribavirin. Gastroenterology. 2010;139(5):1593–601. https://doi.org/10.1053/j.gastro.2010.07.009
92. Scavone C, Sportiello L, Rafaniello C, Mascolo A, Sessa M, Rossi F, et al. New era in treatment options of chronic hepatitis C: Focus on safety of new direct-acting antivirals (DAAs). Expert Opin Drug Saf. 2016;15(sup2):85–100.
93. Tapper EB, Bacon BR, Curry MP, Dieterich DT, Flamm SL, Guest LE, et al. Real-world effectiveness for 12 weeks of ledipasvir-sofosbuvir for genotype 1 hepatitis C: The Trio Health study. J Viral Hepat. 2017;24(1):22–7. https://doi.org/10.1111/jvh.12611
94. Kramer JR, Puenpatom A, Erickson KF, Cao Y, Smith D, El-Serag HB, et al. Real-world effectiveness of elbasvir/grazoprevir In HCV-infected patients in the US veterans affairs healthcare system. J Viral Hepat. 2018;25(11):1270–9. https://doi.org/10.1111/jvh.12937
95. Sise ME, Backman E, Ortiz GA, Hundemer GL, Ufere NN, Chute DF, et al. Effect of Sofosbuvir-Based Hepatitis C Virus Therapy on Kidney Function in Patients with CKD. Clin J Am Soc Nephrol. 2017;12(10):1615–23. https://doi.org/10.2215/CJN.02510317
96. Desnoyer A, Pospai D, Lê MP, Gervais A, Heurgué-Berlot A, Laradi 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. 2016;65(1):40–47. https://doi.org/10.1016/j.jhep.2016.02.044
97. Dumortier J, Bailly F, Pageaux GP, Vallet-Pichard A, Radenne S, HabersetzerF, et al. Sofosbuvir-based antiviral therapy in hepatitis C virus patients with severe renal failure. Nephrol Dial Transplant. 2017;32(12):2065–71.
98. Surendra M, Raju SB, Sridhar N, Vijay Kiran B, Rajesh G, AnveshG, et al. Ledipasvir and Sofosbuvir for untreated HCV genotype 1 infection in end stage renal disease patients: A prospective observational study. Hemodial Int. 2018;22(2):217–21. https://doi.org/10.1111/hdi.12604
99. Roth D, Nelson DR, Bruchfeld A, Liapakis A, Silva M, Monsour H Jr, et al. Grazoprevir plus elbasvir in treatment-naive 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. 2015;386(10003):1537–45. https://doi.org/10.1016/S0140-6736(15)00349-9
100. Reddy KR, Roth D, Bruchfeld A, Hwang P, Haber B, Robertson MN, et al. Elbasvir/grazoprevir does not worsen renal function in patients with hepatitis C virus infection and pre-existing renal disease. Hepatol Res. 2017;47(12):1340–5. https://doi.org/10.1111/hepr.12899
101. Gane E, Lawitz E, Pugatch D, Papatheodoridis G, Bräu N, Brown A, et al. Glecaprevir and Pibrentasvir in Patients with HCV and Severe Renal Impairment. N Engl J Med. 2017;377(15):1448–55. https://doi.org/10.1056/NEJMoa1704053
102. Elbasha E, Greaves W, Roth D, Nwankwo C. Cost-effectiveness of elbasvir/grazoprevir use in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and chronic kidney disease in the United States. J Viral Hepat. 2017;24(4):268–79. https://doi.org/10.1111/jvh.12639
103. Maunoury F, Clément A, Nwankwo C, Levy-Bachelot L, Abergel A, Di Martino V, et al. Cost-effectiveness analysis of elbasvir-grazoprevir regimen for treating hepatitis C virus genotype 1 infection in stage 4-5 chronic kidney disease patients in France. PLoS One. 2018;13(3):e0194329. https://doi.org/10.1371/journal.pone.0194329
104. KDIGO. Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int Suppl. 2018;8(3): 114–120. https://doi.org/10.1016/S2157-1716(18)30010-8
105. Davis MI, Chute DF, Chung RT, Sise ME. When and how can nephrologists treat hepatitis C virus infection in dialysis patients? Semin Dial. 2018;31(1):26–36. https://doi.org/10.1111/sdi.12650
106. Al-Rabadi L, Box T, Singhania G, Al-Marji C, Agarwal A, Hall I, et al. Rationale for treatment of hepatitis C virus infection in end-stage renal disease patients who are not kidney transplant candidates. Hemodial Int. 2018;22 Suppl 1:S45–S52. https://doi.org/10.1111/hdi.12656
107. Cohen-Bucay A, Francis JM, Gordon CE. Timing of hepatitis C virus infection treatment in kidney transplant candidates. Hemodial Int. 2018;22 Suppl 1:S61–S70. https://doi.org/10.1111/hdi.12643
108. Jadoul M, Martin P. Should all dialysis patients with hepatitis C be treated? If so, before or after kidney transplantation? Semin Dial. 2017;30(5):395–7. https://doi.org/10.1111/sdi.12640
109. Sawinski D, Bloom RD. Novel Hepatitis C treatment and the impact on kidney transplantation. Transplantation. 2015;99(12):2458–66. https://doi.org/10.1097/TP.0000000000000847
110. Gisbert JP, García-Buey L, Pajares JM, Moreno-Otero R. Systematic review: Regression of lymphoproliferative disorders after treatment for hepatitis C infection. Aliment Pharmacol Ther. 2005;21(6):653–62. https://doi.org/10.1111/j.1365-2036.2005.02395.x
111. Morales JM, Campistol JM, Domínguez-Gil B, Andrés A, Esforzado N, Oppenheimer F, et al. Long-term experience with kidney transplantation from hepatitis C-positive donors into hepatitis C-positive recipients. Am J Transplant. 2010;10(11):2453–62. https://doi.org/10.1111/j.1600-6143.2010.03280.x
112. Sawinski D, Lee DH, Doyle AM, Blumberg EA. Successful posttransplant treatment of Hepatitis C With Ledipasvir-Sofosbuvir in HIV+ Kidney Transplant Recipients. Transplantation. 2017;101(5):974–79. https://doi.org/10.1097/TP.0000000000001336
113. Bhamidimarri KR, Ladino M, Pedraza F, Guerra G, Mattiazzi A, Chen L, et al. Transplantation of kidneys from hepatitis C-positive donors into hepatitis C virus-infected recipients followed by early initiation of direct-acting antiviral therapy: A single-center retrospective study. Transpl Int. 2017;30(9):865–73. https://doi.org/10.1111/tri.12954
114. Goldberg DS, Abt PL, Reese PP. THINKER trial investigators. Transplanting HCV-infected kidneys into uninfected recipients. N Engl J Med. 2017;377(11):1105.
115. Durand CM, Bowring MG, Brown DM, Chattergoon MA, Massaccesi G, Bair N, et al. THE EXPANDER-1 Trial Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C Virus-Infected donors to noninfected recipients: An open-label nonrandomized trial. Ann Intern Med. 2018;168(8):533–40. https://doi.org/10.7326/M17-2871
116. Colombo M, Aghemo A, Liu H, Zhang J, Dvory-Sobol H, Hyland R, 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. 2017;166(2):109–17. https://doi.org/10.7326/M16-1205
117. Saxena V, Khungar V, Verna EC, Levitsky J, Brown RS Jr, Hassan MA, 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. 2017;66(4):1090–101. https://doi.org/10.1002/hep.29258
118. Reau N, Kwo PY, Rhee S, Brown RS Jr, Agarwal K, Angus P, et al. Glecaprevir/Pibrentasvir treatment in liver or kidney transplant patients with Hepatitis C virus infection. THE MAGELLAN 2 study hepatology. 2018;68(4):1298–307. https://doi.org/10.1002/hep.30046
119. AASLD-IDSA HCV Guidance Panel Hepatitis C Guidance 2018 Update: AASLD-IDSA recommendations for testing, managing, and treating Hepatitis C virus infection. Clin Infect Dis. 2018;67(10):1477–92. https://doi.org/10.1093/cid/ciy585
120. KDIGO. Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int Suppl. 2018;8(3):130–6. https://doi.org/10.1016/S2157-1716(18)30010-8