Kidney Transplantation From Hepatitis C Viremic Deceased Donors to Aviremic Recipients in a Real-world Setting

Abstract

Background. Transplantation of hepatitis C viremic (HCV+) deceased donor kidney transplants (DDKT) into aviremic (HCV-) recipients is a strategy to increase organ utilization. However, there are concerns around inferior recipient outcomes due to delayed initiation of direct-acting antiviral (DAA) therapy and sustained HCV replication when implemented outside of a research setting. Methods. This was a retrospective single-center matched cohort study of DDKT recipients of HCV+ donors (cases) who were matched 1:1 to recipients of HCV-donors (comparators) by age, gender, race, presence of diabetes, kidney donor profile index, and calculated panel-reactive antibody. Data were analyzed using summary statistics, t-tests, and chi-square tests for between-group comparisons, and linear mixed-effects models for longitudinal data. Results. Each group consisted of 50 recipients with no significant differences in baseline characteristics. The 6-mo longitudinal trajectory of serum creatinine and estimated glomerular filtration rate did not differ between groups. All recipients had similar rates of acute rejection and readmissions (all P > 0.05). One case lost the allograft 151 d posttransplant because of acute rejection, and 1 comparator died on postoperative day 7 from cardiac arrest. HCV+ recipients initiated DAA on average 29 ± 11 d posttransplant. Ninety-eight percent achieved sustained virologic response at 4 and 12 wks with the first course of therapy; 1 patient had persistent HCV infection and was cured with a second course of DAA. Conclusions. Aviremic recipients of HCV+ DDKT with delayed DAA initiation posttransplant had similar short-term outcomes compared with matched recipient comparators of HCV-donors.

Review of Renal Transplantation of Hepatitis C Viremic Donor Organs into Aviremic Recipients

“…Durand achieved more success with an extended 4 weeks of prophylactic treatment [36]. However, with delayed treatment, mimicking real-world experience, there were found to be no difference in rejection, readmission, and death [33,37].…”

“…In addition, there are several drug-drug interactions to be aware of as well including immunosuppressants, amiodarone, proton pump inhibitors, azole family drugs [25][26][27]. However, despite all of these considerations, patients in available reports ultimately received treatment with various DAA regimens including glecaprevir/pibrentasvir, elbasvir/grazoprevir, sofosbuvir/ velpatasvir, and sofosbuvir/ledipasvir [19,[28][29][30][31][32][33].…”

“…To date, there has not been evidence to suggest that a real-world delay in initiation of antiviral therapy after kidney transplantation results in higher risks of adverse outcomes. However, more research must be done to confirm the safety of this approach due to low sample size of current studies [33,37]. In addition, with increased use of HCV+ donor solid organ transplantation, there may be modified and expedited insurance authorization for DAA making the agents available while inpatient or very shortly after discharge.…”

Efficacy and Safety of Direct-Acting Antivirals in Kidney Transplantation From HCV-Viremic Donors to Negative Recipients: A Meta-Analysis

“…A total of 124 articles were selected for full-text reading and 112 articles were excluded for different reasons. Eventually, 16 articles ( 21 – 36 ) were included in this study ( Figure 1 ). The 16 studies were published during 2018–2022, including 15 full articles and 1 letter, which were conducted in 3 regions: the USA (14 articles), Germany (1 article), and China (1 article).…”

“…This patient received an HCV+ kidney with 2b subtype, but was treated with LDV/SOF based for the HCV 1a genotype, which did not respond to 2b subtype. In the third study, one HCV 1a-infected recipient, treated with LDV/SOF and without viral resistance testing, neither achieved SVR-4 nor SVR12 with unknown cause, but eventually obtained SVR12 after retreating with sofosbuvir/velpatasvir/voxilaprevir ( 36 ). From the aforementioned studies, it is essential to accurately capture the HCV genotyping and RASs information of donors and recipients to make sure that patients can benefit from the best treatment for their condition.…”