Key words : Hemodialysis, Kidney transplant, Virological response

Introduction

Recurrence of hepatitis C virus (HCV) infection after organ transplant has dreadful complications, including graft failure and fibrosing cholestatic hepatitis.^1,2 Transplant recipients can have a good response with direct-acting antiviral agents (DAAs).

Although a sustained virological response is considered as the virological cure,³ it requires patients to be on dialysis an additional 3 months before undergoing renal transplant, thus increasing risk of HCV reinfection and associated complications. Because the cytopathic properties of HCV can lead to survival risk in renal transplant recipients, we thus aimed to determine HCV recurrence in renal transplant recipients who had achieved an end of treatment response (ETR) before renal transplant. .

Materials and Methods

Our study included renal transplant recipients who were between 18 and 50 years of age and who were treated for HCV before transplant with DAAs. Information on DAAs used by patients during dialysis was obtained from medical records of patients. We also obtained data on patients’ rapid viral response (RVR) and ETR. Achievement of RVR was defined as HCV not detected with polymerase chain reaction (PCR) after 1 month of DAA treatment. Achievement of ETR was defined as no detection of HCV on PCR after end of treatment. As per our institutional protocol, patients on dialysis who did not achieve RVR were treated with 6 months of DAAs. All patients who achieved ETR were then referred for transplant. Kidney transplant recipients who were treated with DAAs and had an HCV PCR test at least 3 months after transplant were enrolled. Transplant recipients with detectable HCV PCR were considered to have HCV recurrence. Patient who refused participation were excluded.

We analyzed data using SPSS version 20 statistical software. Data are presented as mean ± SD for quantitative variables.

Results

Over 1.5 years, 432 patients underwent renal transplant at the Sindh Institute of Urology and Transplantation. Of these patients, 48 were previously treated for HCV with DAAs and were included in our study; most were males (81.1%) with mean age of 28.7 ± 9.4 years.

Pretransplant
All patients had received sofosbuvir, daclatasvir, and ribavirin combination. Most patients received treatment for 3 months (70%); the remaining patients had treatment for 6 months. Only 5% of patients did not achieve RVR. An ETR was achieved in all patients.

Posttransplant
A PCR test of HCV was conducted at a mean duration of 8.3 ± 3.3 months. Laboratory parameters showed total bilirubin level of 3.6 ± 17.5 mg/day, alanine aminotransferase level of 51.5 ± 80.2 IU/L, and gamma-glutamyltransferase level of 133.9 ± 220 IU/L. (Table 1) shows the mean laboratory parameters before and after transplant. Recurrence of HCV after renal transplant was documented in 2 patients (4.2%) (Figure 1).

Discussion

Infection with HCV and chronic kidney disease are major global public health issues. Globally, more than 185 million people have HCV infections.⁴ In developed countries, the prevalence of anti-HCV seropositivity among patients on maintenance hemodialysis ranges between 5% and 60%.⁵ Furthermore, the rate of HCV in hemodialysis patients in Pakistan is 23.7% to 56.6%.⁶

Kidney transplant remains the therapy of choice for patients with end-stage renal disease and HCV infection.⁷ However, patients with HCV infection have increased risk of allograft rejection, proteinuria, diabetes, and fibrosing cholestatic hepatitis after transplant.^1,2

In the era of interferon , patients with HCV after renal transplant were not treated because of graft rejection, whereas relapse rate in recipients who were treated before transplant was 13% despite patients achieving ETR.⁸ For patients who receive highly effective DAAs, it is proposed and practiced to transplant these patients soon after completion of treatment.⁹ In our previous study, in 73 patients on dialysis, 95.8% had sustained virological response at 12 weeks after treatment with sofosbuvir and daclatasvir.¹⁰

Although sustained virological response is considered as the virological cure,³ it requires patients to be to be on dialysis for a longer duration (namely, 3-6 months) before renal transplant, thus increasing risk of breakthrough relapse and de novo HCV infection and associated complications.

Of 48 patients, only 2 renal transplant recipients had HCV recurrence; both recipients died (1 with graft failure and 1 with cryptococcal meningitis). However, overall, 95.8% of our patients had no HCV recurrence. To the best of our knowledge, no study has been performed to address HCV recurrence after transplant in patients treated with DAAs. Although we had a small sample size, we showed that patients who had achieved ETR during dialysis can undergo renal transplant with minimum risk of HCV recurrence.

Conclusions

To our knowledge, this is the first study to document excellent response of DAAs in renal transplant recipients who has been referred early for transplant. Thus, dialysis patients can undergo transplant after achieving ETR.

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