Research ArticleEfficacy and tolerability of interferon-free antiviral therapy in kidney transplant recipients with chronic hepatitis C
Graphical abstract
Introduction
Approximately 5 to 15% of kidney transplant (KT) recipients have chronic hepatitis C. Hepatitis C virus (HCV) infection is associated with an increased risk of mortality in these patients as a consequence of liver disease, higher infection rates and cardiovascular disease [1]. Moreover, HCV infection in KT patients is an independent risk factor for graft loss, and it is associated with proteinuria, chronic rejection, transplant glomerulopathy, post-transplant diabetes and HCV-associated glomerulonephritis [2], [3].
In the interferon era, the treatment of HCV infection in KT recipients was limited due to the high risk of allograft dysfunction and the very modest success in achieving viral eradication [4]. Indeed, interferon-based regimens were not recommended in KT recipients except in cases of life-threatening liver injury [5]. The development of direct-acting antiviral agents (DAAs) against HCV has dramatically reshaped the field of the treatment of hepatitis C. Interferon-free regimens using combinations of second-generation DAAs have consistently returned sustained virological response (SVR) rates of above 90% in immunocompetent patients, with a good safety profile [6], [7]. The efficacy of DAAs therapy in liver transplant recipients is well established [8], [9] and, although published data on DAAs in KT recipients are scarce, preliminarily results are promising [10], [11].
The aim of this study was to evaluate the efficacy and tolerability of DAAs combinations in KT recipients while determining the impact of therapy on renal function and immunosuppressive drug levels, in the largest real-life cohort reported so far.
Section snippets
Patients and methods
This was a retrospective, non-interventional, national, multicentre study of patients treated in routine clinical practice. Data were collected through a National Registry (HEPA-C) under the auspices of the Spanish Association for the Study of the Liver (AEEH) and the Networked Biomedical Research Centre for the Study of the Liver and Digestive Diseases in Spain (CIBEREHD). The study recorded data from KT patients chronically infected with HCV treated with DAAs in eight Spanish referral centres
Patient characteristics and HCV therapy
We report on the data from 103 KT recipients who received an interferon-free antiviral regimen with different combinations of DAAs. Patients’ characteristics are presented in Table 1. Briefly, median age was 55 years, 67% of patients were male and all patients were Caucasian. Median time between KT and the start of anti-HCV therapy was 147 months (range 1–561). Twenty-six (25%) patients had a combined liver/kidney transplant and 4 (4%) a combined pancreatic/kidney transplant. The indication for
Discussion
New DAAs against HCV seem to be a promising antiviral option for KT recipients. Treatment of HCV with DAAs is associated with high response rates and a good safety profile in immunocompetent patients and liver transplant recipients. However, data in the KT population are scarce. We evaluated the safety and effectiveness of DAAs in this retrospective and multicentre study of KT patients treated in routine clinical practice in Spain, being to the best of our knowledge, the largest real-life
Financial support
The study received support by the Spanish Health Ministry (Plan Estratégico Nacional contra la hepatitis C). XF: received support in part by Instituto de Salud Carlos III (PI15/00151), Ministerio de Economía y Competitividad, co-funded by Fondo Europeo de Desarrollo Regional, Unión Europea, Una manera de hacer Europa.
Conflict of interest
IF has served as speaker and consultant for Janssen, Abbvie, MSD and Gilead. RMG has served as consultant and speaker for BMS, Abbvie, MSD and Gilead. JMP has served as speaker and advisor for Janssen, BMS, Abbvie and Gilead, and as speaker for MSD. LC has served as speaker and consultant for Abbvie, BMS, Gilead and Janssen. MP has served as speaker and advisor for Abbvie, BMS, Gilead and Janssen. JC has served as speaker and advisor for Janssen, BMS, Abbvie, MSD and Gilead. JLC has served as
Authors’ contributions
IF: study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript. MCL: study concept and design, acquisition of data, interpretation of data, critical revision of the manuscript for important intellectual content. XF: acquisition of data, interpretation of data and critical revision of the manuscript for important intellectual content. NP: analysis and interpretation of data. RMG, JMP, CB, NE, AA, MP, LC, JC, JLC: acquisition of data. OH: data
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