Chronic hepatitis C virus infection (HCV) has a negative impact on the long-term survival of recipients of kidney transplants. HCV should be treated in hemodialyzed patients before their enlistment for kidney transplantation in order to avoid the reactivation of virus after transplantation. Direct-acting antivirals represent the current standard of care in hemodialyzed patients with HCV genotypes 1 and 4; in patients with genotypes 2 or 3, the optimal regimen is yet to be established. Sofosbuvir (SOF) and daclatasvir (DCV) represent an antiviral pangenotypic regimen with favorable pharmacokinetics in hemodialyzed patients. We retrospectively evaluated safety and efficacy of the combination of SOF and DCV in the treatment of genotype 3a chronic HCV in six male patients (mean age of 39 years, range 25-53 years) with end-stage renal disease on maintenance hemodialysis; these patients were treated with a reduced dose of SOF (one half of a 400 mg tablet) and 60 mg of DCV once daily. The anticipated treatment duration was 12 weeks. Initial HCV RNA ranged from 120,000 to 11,000,000 IU/mL. Two of the six patients had compensated liver cirrhosis based on shear-wave elastography result. All of the patients completed a 12-week treatment. Viremia became negative on treatment and remained negative 12 weeks after the end of therapy in all the patients. All of them (6/6, 100%) achieved sustained virological response, including two with cirrhosis and two with HCV RNA >6,000,000 IU/mL. The treatment was well tolerated: none of the patients presented with a serious adverse event requiring hospital admission and none had anemia or any significant changes in blood count. One patient had a short period of diarrhea, which was resolved with antibiotic treatment. The combination of reduced-dose SOF and full-dose DCV, daily, was a safe and effective treatment in our group of hemodialyzed patients infected with HCV genotype 3.

Department of Anesthesiology Resuscitation and Intensive Care Institute for Clinical and Experimental Medicine

Department of Hepatogastroenterology Institute for Clinical and Experimental Medicine

Dialysis Center Motol Fresenius Medical Care Prague Czech Republic

Institute of Medical Biochemistry and Laboratory Medicine General University Hospital Charles University

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Goodkin DA, Bieber B, Gillespie B, Robinson BM, Jadoul M. Hepatitis C infection is very rarely treated among hemodialysis patients. Am J Nephrol. 2013;38(5):405–412. PubMed

European Association for the Study of the Liver EASL recommendations on treatment of hepatitis C 2016. J Hepatol. 2017;66(1):153–194. PubMed

Pockros PJ, Reddy KR, Mantry PS, 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. 2016;150(7):1590–1598. PubMed

Roth D, Nelson DR, Bruchfeld A, 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):1537–1545. PubMed

Espinosa M, Martin-Malo A, Alvarez de Lara MA, Aljama P. Risk of death and liver cirrhosis in anti-HCV-positive long-term haemodialysis patients. Nephrol Dial Transplant. 2001;16(8):1669–1674. PubMed

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):1584–1593. PubMed

Butt AA, Skanderson M, McGinnis KA, et al. Impact of hepatitis C virus infection and other comorbidities on survival in patients on dialysis. J Viral Hepat. 2007;14(10):688–696. PubMed

Fabrizi F, Takkouche B, Lunghi G, Dixit V, Messa P, Martin P. The impact of hepatitis C virus infection on survival in dialysis patients: meta-analysis of observational studies. J Viral Hepat. 2007;14(10):697–703. PubMed

Fabrizi F, Dixit V, Bunnapradist S, Martin P. Meta-analysis: the dialysis mode and immunological response to hepatitis B virus vaccine in dialysis population. Aliment Pharmacol Ther. 2006;23(8):1105–1112. PubMed

Mathurin P, Mouquet C, Poynard T, et al. Impact of hepatitis B and C virus on kidney transplantation outcome. Hepatology. 1999;29(1):257–263. PubMed

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):2244–2252. PubMed

Legendre C, Garrigue V, Le Bihan C, et al. Harmful long-term impact of hepatitis C virus infection in kidney transplant recipients. Transplantation. 1998;65(5):667–670. PubMed

Bruchfeld A, Wilczek H, Elinder CG. Hepatitis C infection, time in renal-replacement therapy, and outcome after kidney transplantation. Transplantation. 2004;78(5):745–750. PubMed

Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368(20):1878–1887. PubMed

Desnoyer A, Pospai D, Le MP, 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. PubMed

Singh T, Guirguis J, Anthony S, Rivas J, Hanouneh IA, Alkhouri N. Sofosbuvir-based treatment is safe and effective in patients with chronic hepatitis C infection and end stage renal disease: a case series. Liver Int. 2016;36(6):802–806. PubMed

Dumortier J, Bailly F, Pageaux GP, et al. Sofosbuvir-based antiviral therapy in hepatitis C virus patients with severe renal failure. Nephrol Dial Transplant. 2016 Oct 19; Epub. PubMed

Beinhardt S, Al Zoairy R, Ferenci P, et al. DAA-based antiviral treatment of patients with chronic hepatitis C in the pre- and postkidney transplantation setting. Transpl Int. 2016;29(9):999–1007. PubMed

Perumpail RB, Wong RJ, Ha LD, et al. Sofosbuvir and simeprevir combination therapy in the setting of liver transplantation and hemodialysis. Transpl Infect Dis. 2015;17(2):275–278. PubMed

Saab S, M AJ, S NB, et al. Use of sofosbuvir-based treatment of chronic hepatitis C in liver transplant recipients on hemodialysis. J Clin Gastroenterol. 2017;51(2):167–173. PubMed

Nazario HE, Ndungu M, Modi AA. Sofosbuvir and simeprevir in hepatitis C genotype 1-patients with end-stage renal disease on haemodialysis or GFR <30 ml/min. Liver Int. 2016;36(6):798–801. PubMed

Hundemer GL, Sise ME, Wisocky J, et al. Use of sofosbuvir-based direct-acting antiviral therapy for hepatitis C viral infection in patients with severe renal insufficiency. Infect Dis (Lond) 2015;47(12):924–929. PubMed PMC

Gerber L, Kasper D, Fitting D, et al. Assessment of liver fibrosis with 2-D shear wave elastography in comparison to transient elastography and acoustic radiation force impulse imaging in patients with chronic liver disease. Ultrasound Med Biol. 2015;41(9):2350–2359. PubMed

European Medicines Agency Sovaldi: Příloha I; souhrn údajů o přípravku [Sovaldi: Annex I; summary of product characteristics] [Accessed February 1, 2017]. Available from: http://www.ema.europa.eu/docs/cs_CZ/document_library/EPAR_-_Product_Information/human/002798/WC500160597.pdf. Czech.

European Association for the Study of the Liver EASL recommendations on treatment of hepatitis C 2015. [Accessed February 1, 2017]. Available from: http://www.easl.eu/research/our-contributions/clinical-practice-guidelines/detail/recommendations-on-treatment-of-hepatitis-c-2015. PubMed

European Association for the Study of the Liver EASL recommendations on treatment of hepatitis C 2014. [Accessed February 1, 2017]. Available from: http://www.easl.eu/discover/news/easl-recommendations-on-treatment-of-hepatitis-c-2014. PubMed

Garimella T, Wang R, Luo WL, et al. Single-dose pharmacokinetics and safety of daclatasvir in subjects with renal function impairment. Antivir Ther. 2015;20(5):535–543. PubMed

Gane E, Robson RA, Bonacin M. Safety, anti-viral-efficacy and Pharmacokinetics (PK) of Sofosbuvir (SOF) in patients with severe renal impairment. Hepatology. 2014;60(Suppl S1):667A.

Burra P, Rodriguez-Castro KI, Marchini F, et al. Hepatitis C virus infection in end-stage renal disease and kidney transplantation. Transpl Int. 2014;27(9):877–891. PubMed

Gevers TJ, Burger D, Schipper-Reintjes E, Kooistra MP, Richter C. Full-dose sofosbuvir and daclatasvir for chronic hepatitis C infection in haemodialysis patients. Neth J Med. 2016;74(5):225–227. PubMed

Nelson DR, Cooper JN, Lalezari JP, et al. All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study. Hepatology. 2015;61(4):1127–1135. PubMed PMC

Alonso S, Riveiro-Barciela M, Fernandez I, et al. Effectiveness and safety of sofosbuvir-based regimens plus an NS5A inhibitor for patients with HCV genotype 3 infection and cirrhosis. Results of a multicenter real-life cohort. J Viral Hepat. 2017;24(4):304–311. PubMed

Welzel TM, Petersen J, Herzer K, et al. Daclatasvir plus sofosbuvir, with or without ribavirin, achieved high sustained virological response rates in patients with HCV infection and advanced liver disease in a real-world cohort. Gut. 2016;65(11):1861–1870. PubMed PMC

Saxena V, Koraishy FM, Sise ME, et al. Safety and efficacy of sofosbuvir-containing regimens in hepatitis C-infected patients with impaired renal function. Liver Int. 2016;36(6):807–816. PubMed PMC

Chlibek R, Smetana J, Sosovickova R, et al. Hepatitis C prevalence in the general adult population in the Czech Republic – results of a seroprevalence study. PLoS One. 2017;12(4):e0175525. PubMed PMC

Sperl J, Frankova S, Senkerikova R, et al. Relevance of low viral load in haemodialysed patients with chronic hepatitis C virus infection. World J Gastroenterol. 2015;21(18):5496–5504. PubMed PMC

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