Elsevier

Journal of Hepatology

Volume 66, Issue 4, April 2017, Pages 718-723
Journal of Hepatology

Research Article
Efficacy and tolerability of interferon-free antiviral therapy in kidney transplant recipients with chronic hepatitis C

https://doi.org/10.1016/j.jhep.2016.12.020Get rights and content

Background & Aims

The development of direct-acting antiviral agents (DAAs) is a major step forward in the treatment of hepatitis C (HCV). The aims of the study were to evaluate the efficacy and tolerability of DAAs in kidney transplant (KT) recipients.

Methods

Hepa-C is a Spanish registry of patients treated with DAAs in which clinical, virological and analytical data were prospectively included. We report on the data from 103 KT recipients who received DAAs.

Results

The most commonly used DAAs combinations were sofosbuvir/ledipasvir (n = 59, 57%) and sofosbuvir + daclatasvir (n = 18, 17%). Ribavirin was used in 41% of patients. Sustained viral response after 12 weeks (SVR12) rate was 98%. Grade 2 or 3 anemia appeared in 14 (33%) of patients receiving ribavirin and in 9 (15%) without (p = 0.03). There were three episodes of acute humoral graft rejection. No patient discontinued therapy due to adverse events. Importantly, 57 (55%) patients required immunosuppression dose adjustment. Overall, there were no statistically significant differences in the mean level of serum creatinine, eGFR and proteinuria before and after treatment. Nonetheless, seventeen (16%) patients experienced renal dysfunction (increase in serum creatinine >25%) during antiviral therapy, of whom 65% were cirrhotic in comparison with only 29% cirrhotic patients who did not develop significant renal dysfunction (p = 0.004).

Conclusions

Antiviral therapy with DAAs was highly efficacious and safe in KT recipients. Nevertheless, a non-negligible number of patients, most of them cirrhotic, developed mild allograft dysfunction and a significant proportion of patients required immunosuppression dose adjustment, warranting a close follow-up during therapy.

Lay summary

Infection by hepatitis C virus is often found in kidney transplant patients and its presence increases mortality and graft failure. We investigated the efficacy and safety of the new direct-acting hepatitis C antivirals in this population, in which previous information is scarce. Our data shows that, as occurs in the non-transplant setting, new anti-HCV antivirals are highly efficacious kidney transplant patients. Overall, this therapy is also quite safe, although worsening of renal function is observed in 16% of patients warranting a close follow-up observation of graft function during antiviral therapy.

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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