Abstract
Chronic kidney disease represents a global health problem. Chronic hepatitis C virus (HCV) infection is prevalent in patients with end stage renal disease (ESRD) on hemodialysis (HD) and in renal transplant recipients with significant impact on morbidity and mortality. Furthermore, HCV can cause various forms of glomerulopathy with the predominant type being cryglobulinemia associated membranoproliferative glomerulonephritis. Liver enzymes are traditionally used as markers of liver injury; however, there is wide variation in aminotransferase levels in patients with ESRD. Therefore, diagnosis of chronic hepatitis C (CHC) in patients with ESRD is based on HCV antibody testing and further confirmation with polymerase chain reaction testing. Current standard therapy for CHC is composed of pegylated interferon and ribavirin. However, this combination is challenging in patients with ESRD due to its tolerability. We describe in this review relevant issues in epidemiology, diagnosis and management of CHC in ESRD, HD and renal transplant recipients.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Poynard T, Yuen MF, Ratziu V, Lai CL. Viral hepatitis C. Lancet. 2003;362:2095–100.
Finelli L, Miller JT, Tokars JI, et al. National surveillance of dialysis-associated diseases in the United States, 2002. Semin Dial. 2005;18(1):52–61.
Di Napoli A, Pezzotti P, Di Lallo D, et al. Lazio dialysis registry. Epidemiology of hepatitis C virus among long-term dialysis patients: a 9-year study in an Italian region. Am J Kidney Dis. 2006;48(4):629–37.
Fabrizi F, Martin P, Ponticelli C. Hepatitis C virus infection and renal transplantation. Am J Kidney Dis. 2001;38(5):919–34.
Furusyo N, Hayashi J, Kanamoto-Tanaka Y, et al. Liver damage in hemodialysis patients with hepatitis C virus viremia: a prospective 10-year study. Dig Dis Sci. 2000;45(11):2221–8.
Wreghitt TG. Blood-borne virus infections in dialysis units–a review. Rev Med Virol. 1999;9(2):101–9.
Amiri ZM, Shakib AJ, Toorchi M. Seroprevalence of hepatitis C and risk factors in haemodialysis patients in Guilan, Islamic Republic of Iran. East Mediterr Health J. 2005;11(3):372–6.
Fissell RB, Bragg-Gresham JL, Woods JD, et al. Patterns of hepatitis C prevalence and seroconversion in hemodialysis units from three continents:the DOPPS. Kidney Int. 2004;65(6):2335–42.
Sypsa V, Psichogiou M, Katsoulidou A, et al. Incidence and patterns of hepatitis C virus seroconversion in a cohort of hemodialysis patients. Am J Kidney Dis. 2005;45(2):334–43.
Kalantar-Zadeh K, Kilpatrick RD, McAllister CJ, et al. Hepatitis C virus and death risk in hemodialysis patients. J Am Soc Nephrol. 2007;18(5):1584–93.
Espinosa M, Martn-Malo A, Ojeda R, et al. Marked reduction in the prevalence of hepatitis C virus infection in hemodialysis patients: causes and consequences. Am J Kidney Dis. 2004;43(4):685–9.
O’Brien SF, Yi QL, Fan W, et al. Current incidence and estimated residual risk of transfusion-transmitted infections in donations made to Canadian blood services. Transfusion. 2007;47(2):316–25.
Moghaddam SM, Alavian SM, Kermani NA. Hepatitis C and renal transplantation: a review on historical aspects and current issues. Rev Med Virol. 2008;18(6):375–86.
Romero E, Galindo P, Bravo JA, et al. Hepatitis C virus infection after renal transplantation. Transplant Proc. 2008;40(9):2933–5.
Widell A, Månsson S, Persson NH, et al. Hepatitis C superinfection in hepatitis C virus (HCV)-infected patients transplanted with an HCV-infected kidney. Transplantation. 1995;60(7):642–7.
Pereira BJ, Wright TL, Schmid CH, et al. Screening and confirmatory testing of cadaver organ donors for hepatitis C virus infection: a U.S. National collaborative study. Kidney Int. 1994;46(3):886–92.
Pereira BJ, Milford EL, Kirkman RL, et al. Prevalence of hepatitis C virus RNA in organ donors positive for hepatitis C antibody and in the recipients of their organs. N Engl J Med. 1992;327(13):910–5.
Kirk AD, Heisey DM, D’Alessandro AM, et al. Clinical hepatitis after transplantation of hepatitis C virus-positive kidneys: HLA-DR3 as a risk factor for the development of posttransplant hepatitis. Transplantation. 1996;62(12):1758–62.
Natov SN, Lau JY, Ruthazer R, et al. Hepatitis C virus genotype does not affect patient survival among renal transplant candidates. The New England organ bank hepatitis C study group. Kidney Int. 1999;56(2):700–6.
Pereira BJ, Levey AS. Hepatitis C virus infection in dialysis and renal transplantation. Kidney Int. 1997;51(4):981–99.
Wolf PL, Williams D, Coplon N, Coulson AS. Low aspartate transaminase activity in serum of patients undergoing chronic hemodialysis. Clin Chem. 1972;18(6):567–8.
Fabrizi F, Lunghi G, Finazzi S, et al. Decreased serum aminotransferase activity in patients with chronic renal failure: impact on the detection of viral hepatitis. Am J Kidney Dis. 2001;38(5):1009–15.
Lemos LB, Perez RM, Lemos MM, et al. Hepatitis C among predialysis patients: prevalence and characteristics in a large cohort of patients. Nephron Clin Pract. 2008;108(2):c135–40.
Souza JF, Longui CA, Miorin LA, Sens YA. Gamma-glutamyltransferase activity in chronic dialysis patients and renal transplant recipients with hepatitis C virus infection. Transplant Proc. 2008;40(5):1319–23.
Nishida C, Uto H, Oketani M, et al. Clinical significance of alanine aminotransferase levels and the effect of ursodeoxycholic acid in hemodialysis patients with chronic hepatitis C. J Gastroenterol. 2010;45(3):326–34.
Bukh J, Wantzin P, Krogsgaard K, et al. High prevalence of hepatitis C virus (HCV) RNA in dialysis patients: failure of commercially available antibody tests to identify a significant number of patients with HCV infection. Copenhagen dialysis HCV study group. J Infect Dis. 1993;168(6):1343–8.
Schneeberger PM, Keur I, van der Vliet W, et al. Hepatitis C virus infections in dialysis centers in The Netherlands: a national survey by serological and molecular methods. J Clin Microbiol. 1998;36(6):1711–5.
Okuda K, Hayashi H, Yokozeki K, Irie Y. Destruction of hepatitis C virus particles by haemodialysis. Lancet. 1996;347(9005):909–10.
Gane E, Pilmore H. Management of chronic viral hepatitis before and after renal transplantation. Transplantation. 2002;74(4):427–37.
Glicklich D, Thung SN, Kapoian T, et al. Comparison of clinical features and liver histology in hepatitis C-positive dialysis patients and renal transplant recipients. Am J Gastroenterol. 1999;94(1):159–63.
Sterling RK, Sanyal AJ, Luketic VA, et al. Chronic hepatitis C infection in patients with end stage renal disease: characterization of liver histology and viral load in patients awaiting renal transplantation. Am J Gastroenterol. 1999;94(12):3576–82.
Martin P, Carter D, Fabrizi F, et al. Histopathological features of hepatitis C in renal transplant candidates. Transplantation. 2000;69(7):1479–84.
Ozdoğan M, Ozgür O, Boyacioğlu S, et al. Percutaneous liver biopsy complications in patients with chronic renal failure. Nephron. 1996;74(2):442–3.
Ahmad A, Hasan F, Abdeen S, et al. Transjugular liver biopsy in patients with end-stage renal disease. J Vasc Interv Radiol. 2004;15(3):257–60.
Degos F, Pol S, Chaix ML, et al. The tolerance and efficacy of interferon-alpha in haemodialysis patients with HCV infection: a multicentre, prospective study. Nephrol Dial Transplant. 2001;16(5):1017–23.
Huwart L, Sempoux C, Vicaut E, et al. Magnetic resonance elastography for the noninvasive staging of liver fibrosis. Gastroenterology. 2008;135(1):32–40.
Talwalkar JA, Kurtz DM, Schoenleber SJ, et al. Ultrasound-based transient elastography for the detection of hepatic fibrosis: systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2007;5(10):1214–20.
Shaheen AA, Myers RP. Diagnostic accuracy of the aspartate aminotransferase-to-platelet ratio index for the prediction of hepatitis C-related fibrosis: a systematic review. Hepatology. 2007;46(3):912–21.
• Becker VR, Badiani RG, Lemos LB, et al.: Factors associated with the progression of hepatic fibrosis in end-stage kidney disease patients with hepatitis C virus infection. Eur J Gastroenterol Hepatol. 2009;21(12):1395–9. Evaluation of factors associated with disease progression in HCV in the context of end-stage kidney disease.
Schiavon LL, Schiavon JL, Filho RJ, et al. Simple blood tests as noninvasive markers of liver fibrosis in hemodialysis patients with chronic hepatitis C virus infection. Hepatology. 2007;46(2):307–14.
Muñoz R, Ramírez E, Fernandez I, et al. Correlation between fibroscan, liver biopsy, and clinical liver function in patients with hepatitis C virus infection after renal transplantation. Transplant Proc. 2009;41(6):2425–6.
McHutchison JG, Gordon SC, Schiff ER, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis interventional therapy group. N Engl J Med. 1998;339(21):1485–92.
Wills RJ. Clinical pharmacokinetics of interferons. Clin Pharmacokinet. 1990;19(5):390–9.
Bailon P, Palleroni A, Schaffer CA, et al. Rational design of apotent, long-lasting form of interferon: a 40 kDa branched polyethylene glycol-conjugated interferon alpha-2a for the treatment of hepatitis C. Bioconjug Chem. 2001;12:195–202.
Uchihara M, Izumi N, Sakai Y, et al. Interferon therapy for chronic hepatitis C in hemodialysis patients: increased serum levels of interferon. Nephron. 1998;80(1):51–6.
Gupta SK, Pittenger AL, Swan SK, et al. Single-dose pharmacokinetics and safety of pegylated interferon-alpha2b in patients with chronic renal dysfunction. J Clin Pharmacol. 2002;42(10):1109–15.
http://www.gene.com/gene/products/information/pegasys/pdf/pi.pdf. Pegasys prescribing information. Accessed 15 July 2011.
Dusheiko G, Main J, Thomas H, et al. Ribavirin treatment for patients with chronic hepatitis C: results of a placebo-controlled study. J Hepatol. 1996;25(5):591–8.
Page T, Connor JD. The metabolism of ribavirin in erythrocytes and nucleatedcells. Int J Biochem. 1990;22(4):379–83.
http://www.spfiles.com/pirebetol.pdf. Rebetol prescribing information. Accessed 15 July 2011.
Bruchfeld A, Lindahl K, Schvarcz R, Ståhle L. Dosage of ribavirin in patients with hepatitis C should be based on renal function: a population pharmacokinetic analysis. Ther Drug Monit. 2002;24(6):701–8.
Glue P. The clinical pharmacology of ribavirin. Semin Liver Dis. 1999;19 Suppl 1:17–24.
Tsui JI, Vittinghoff E, Shlipak MG, et al. Association of hepatitis C seropositivity with increased risk for developing end-stage renal disease. Arch Intern Med. 2007;167(12):1271–6.
Sabry AA, Sobh MA, Irving WL, et al. A comprehensive study of the association between hepatitis C virus and glomerulopathy. Nephrol Dial Transplant. 2002;17(2):239–45.
Stehman-Breen C, Alpers CE, Fleet WP, Johnson RJ. Focal segmental glomerular sclerosis among patients infected with hepatitis C virus. Nephron. 1999;81(1):37–40.
Baid S, Pascual M, Williams Jr WW, et al. Renal thrombotic microangiopathy associated with anticardiolipin antibodies in hepatitis C-positive renal allograft recipients. J Am Soc Nephrol. 1999;10(1):146–53.
Markowitz GS, Cheng JT, Colvin RB, et al. Hepatitis C viral infection is associated with fibrillary glomerulonephritis and immunotactoid glomerulopathy. J Am Soc Nephrol. 1998;9(12):2244–52.
D’Amico G. Renal involvement in hepatitis C infection: cryoglobulinemic glomerulonephritis. Kidney Int. 1998;54(2):650–71.
Tarantino A, Campise M, Banfi G, et al. Long-term predictors of survival in essential mixed cryoglobulinemic glomerulonephritis. Kidney Int. 1995;47(2):618–23.
Fabrizi F, Colucci P, Ponticelli C, Locatelli F. Kidney and liver involvement in cryoglobulinemia. Semin Nephrol. 2002;22(4):309–18.
Ruggenenti P, Schieppati A, Remuzzi G. Progression, remission, regression of chronic renal diseases. Lancet. 2001;357(9268):1601–8.
Chadban SJ, Atkins RC. Glomerulonephritis. Lancet. 2005;365:1797–806.
Misiani R, Bellavita P, Fenili D, et al. Interferon alfa-2a therapy in cryoglobulinemia associated with hepatitis C virus. N Engl J Med. 1994;330(11):751–6.
Sabry AA, Sobh MA, Sheaashaa HA, et al. Effect of combination therapy (ribavirin and interferon) in HCV-related glomerulopathy. Nephrol Dial Transplant. 2002;17(11):1924–30.
Cua IH, Kwan V, Henriquez M, et al. Long term suppressive therapy with pegylated interferon for chronic hepatitis C associated membranoproliferative glomerulonephritis. Gut. 2006;55(10):1521–2.
Bruchfeld A, Lindahl K, Ståhle L, et al. Interferon and ribavirin treatment in patients with hepatitis C-associated renal disease and renal insufficiency. Nephrol Dial Transplant. 2003;18(8):1573–80.
Bloom RD, Lake JR. Emerging issues in hepatitis C virus-positive liver and kidney transplant recipients. Am J Transplant. 2006;6(10):2232–7.
Abbott KC, Bucci JR, Matsumoto CS, et al. Hepatitis C and renal transplantation in the era of modern immunosuppression. J Am Soc Nephrol. 2003;14(11):2908–18.
Koziolek MJ, Scheel A, Bramlage C, et al. Effective treatment of hepatitis C-associated immune-complex nephritis with cryoprecipitate apheresis and antiviral therapy. Clin Nephrol. 2007;67(4):245–9.
Ruggenenti P, Chiurchiu C, Abbate M, et al. Rituximab for idiopathic membranous nephropathy: who can benefit? Clin J Am Soc Nephrol. 2006;1(4):738–48.
Ahmed MS, Wong CF. Should rituximab be the rescue therapy for refractory mixed cryoglobulinemia associated with hepatitis C? J Nephrol. 2007;20(3):350–6.
Saadoun D, Resche-Rigon M, Sene D, et al. Rituximab combined with Peg-interferon-ribavirin in refractory hepatitis C virus-associated cryoglobulinaemia vasculitis. Ann Rheum Dis. 2008;67(10):1431–6.
Espinosa M, Martin-Malo A, Alvarez de Lara MA, et al. Natural history of acute HCV infection in hemodialysis patients. Clin Nephrol. 2002;58(2):143–50.
Gürsoy M, Gür G, Arslan H, et al. Interferon therapy in haemodialysis patients with acute hepatitis C virus infection and factors that predict response to treatment. J Viral Hepat. 2001;8(1):70–7.
Al-Harbi AS, Malik GH, Subaity Y, et al. Treatment of acute hepatitis C virus infection with alpha interferon in patients on hemodialysis. Saudi J Kidney Dis Transpl. 2005;16(3):293–7.
• Liu CH, Liang CC, Liu CJ, et al.: Pegylated interferon alfa-2a monotherapy for hemodialysis patients with acute hepatitis C. Clin Infect Dis. 2010;51(5):541–9. Experience of treating acute HCV infection in cohort of 35 patients with Pegylated interferon.
Shu KH, Lan JL, Wu MJ, et al. Ultralow-dose alpha-interferon plus ribavirin for the treatment of active hepatitis C in renal transplant recipients. Transplantation. 2004;77(12):1894–6.
Schmitz V, Kiessling A, Bahra M, et al. Peginterferon alfa-2b plus ribavirin for the treatment of hepatitis C recurrence following combined liver and kidney transplantation. Ann Transplant. 2007;12(3):22–7.
Cruzado JM, Casanovas-Taltavull T, Torras J, et al. Pretransplant interferon prevents hepatitis C virus-associated glomerulonephritis in renal allografts by HCV-RNA clearance. Am J Transplant. 2003;3(3):357–60.
•• Fabrizi F, Dixit V, Messa P, Martin P: Interferon monotherapy of chronic hepatitis C in dialysis patients: meta-analysis of clinical trials. J Viral Hepat. 2008 Feb;15(2):79–88. Important meta-analysis of trials in dialysis patients using Interferon monotherapy.
•• Fabrizi F, Dixit V, Messa P, Martin P: Pegylated interferon monotherapy of chronic hepatitis C in dialysis patients: Meta-analysis of clinical trials. J Med Virol. 2010;82(5):768–75. Important meta-analysis of trials in dialysis patients using Pegylated Interferon monotherapy.
Mousa DH, Abdalla AH, Al-Shoail G, et al. Alpha-interferon with ribavirin in the treatment of hemodialysis patients with hepatitis C. Transplant Proc. 2004;36(6):1831–4.
Bruchfeld A, Ståhle L, Andersson J, Schvarcz R. Ribavirin treatment in dialysis patients with chronic hepatitis C virus infection–a pilot study. J Viral Hepat. 2001;8(4):287–92.
Bruchfeld A, Lindahl K, Reichard O, et al. Pegylated interferon and ribavirin treatment for hepatitis C in haemodialysis patients. J Viral Hepat. 2006;13(5):316–21.
van Leusen R, Adang RP, de Vries RA, et al. Pegylated interferon alfa-2a (40 kD) and ribavirin in haemodialysis patients with chronic hepatitis C. Nephrol Dial Transplant. 2008;23(2):721–5.
Rendina M, Schena A, Castellaneta NM, et al. The treatment of chronic hepatitis C with peginterferon alfa-2a (40 kDa) plus ribavirin in haemodialysed patients awaiting renal transplant. J Hepatol. 2007;46(5):768–74.
Magnone M, Holley JL, Shapiro R, et al. Interferon-alpha-induced acute renal allograft rejection. Transplantation. 1995;59(7):1068–70.
Rostaing L, Modesto A, Baron E, et al. Acute renal failure in kidney transplant patients treated with interferon alpha 2b for chronic hepatitis C. Nephron. 1996;74(3):512–6.
Fabrizi F, Lunghi G, Dixit V, Martin P. Meta-analysis: anti-viral therapy of hepatitis C virus-related liver disease in renal transplant patients. Aliment Pharmacol Ther. 2006;24(10):1413–22.
Poordad F, McCone Jr J, Bacon BR, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364(13):1195–206.
Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364(25):2405–16.
Van Heeswijk R, Vandevoorde A, Boogaerts G, et al.: The effect of severe renal impairment on the pharmacokinetics of the investigational HCV protease inhibitor telaprevir. Journal of Hepatology. Conference: 46th Annual Meeting of the European Association for the Study of the Liver, International Liver Congress 2011 Berlin Germany. 54(pp S492), 2011.
http://www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf. Victrelis prescribing information. Accessed 15 July 2011.
Disclosure
No potential conflicts of interest relevant to this article were reported.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Al-Freah, M.A.B., Zeino, Z. & Heneghan, M.A. Management of Hepatitis C in Patients with Chronic Kidney Disease. Curr Gastroenterol Rep 14, 78–86 (2012). https://doi.org/10.1007/s11894-011-0238-0
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11894-011-0238-0