RESUMO
Long-term liver outcome in hepatitis C virus (HCV)-negative kidney recipients who acquired HCV infection from viremic donors is of intense interest in the transplant community. We evaluated the incidence of fibrosis in liver biopsy specimens of recipients who were transplanted with HCV-infected grafts. Methods: Patients were evaluated in the hepatology clinic, and 29 patients agreed to undergo liver biopsy. The liver histology was scored by the meta-analysis of histological data in viral hepatitis scoring system and was assessed by hepatopathologists. The fibrosis score was compared between patients who initiated direct-acting antiviral (DAA) within 6 wk (n = 6) and after 6 wk (n = 29). Results: Eighty-nine aviremic patients were transplanted with HCV-infected grafts between March 2018 and October 2019. All patients developed HCV infection and were treated with DAA treatment after kidney transplantation (median, 70 d; interquartile range, 55-85 d). All patients (n = 89) achieved sustained virologic response with DAA. The median follow-up time from kidney transplant to liver biopsy was 28 mo (interquartile range, 26-30 mo). Twenty-five patients (86%) had F0, and 4 patients (14%) had F1 fibrosis. No patient had advanced fibrosis (F3-F4). Grade 1 inflammation was present in 6 (21%) patients, whereas 26 (90%) patients had iron accumulation in the hepatocytes and reticuloendothelial cells. There was no difference in the fibrosis score between patients who received treatment within 6 wk versus after 6 wk (P = 0.55). Conclusions: Kidney transplantation of HCV-infected graft to HCV-negative recipients is safe and has no long-term liver-related complications with successful eradication of HCV. In our cohort, delayed treatment did not affect sustained virologic response or liver histology.
RESUMO
Kidney transplantation (KT) from deceased donors with hepatitis C virus (HCV) into HCV-negative recipients has become more common. However, the risk of complications such as BK polyomavirus (BKPyV) remains unknown. We assembled a retrospective cohort at four centers. We matched recipients of HCV-viremic kidneys to highly similar recipients of HCV-aviremic kidneys on established risk factors for BKPyV. To limit bias, matches were within the same center. The primary outcome was BKPyV viremia ≥1000 copies/ml or biopsy-proven BKPyV nephropathy; a secondary outcome was BKPyV viremia ≥10 000 copies/ml or nephropathy. Outcomes were analyzed using weighted and stratified Cox regression. The median days to peak BKPyV viremia level was 119 (IQR 87-182). HCV-viremic KT was not associated with increased risk of the primary BKPyV outcome (HR 1.26, p = .22), but was significantly associated with the secondary outcome of BKPyV ≥10 000 copies/ml (HR 1.69, p = .03). One-year eGFR was similar between the matched groups. Only one HCV-viremic kidney recipient had primary graft loss. In summary, HCV-viremic KT was not significantly associated with the primary outcome of BKPyV viremia, but the data suggested that donor HCV might elevate the risk of more severe BKPyV viremia ≥10 000 copies/ml. Nonetheless, one-year graft function for HCV-viremic recipients was reassuring.
Assuntos
Vírus BK , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Hepacivirus , Humanos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Infecções Tumorais por Vírus/etiologia , ViremiaRESUMO
Kidney transplantation (KT) from hepatitis C virus infected (HCV+) donors to HCV negative recipients achieve excellent graft function but have relatively higher rates of post-KT co-infections presumably due to prolonged HCV viremia in transmission-and-treat approach. Ezetimibe acts as an antagonist of Niemann-Pick C1-Like 1 receptor required for HCV entry and theoretically can reduce HCV viremia. However, no data is available to examine the role of ezetimibe as a bridge therapy between KT surgery and direct acting antiviral (DAA) initiation. A retrospective cohort study including 70 HCV+ to HCV negative KT recipients from Methodist University Hospital and Vanderbilt University Medical Center was performed to determine the association between ezetimibe usage and HCV viremia. Twenty patients received ezetimibe daily while 50 patients did not. Primary outcome of study was mean HCV RNA level at 1-2 weeks post-KT and before initiation of DAA. Median (IQR) viral load (VL) in log copies/ml was one log lower in ezetimibe group versus non-ezetimibe group (4.1 [3.7-5.3] vs. 5.1 [4.4-5.5], P = .01), and highest VL was also lower in ezetimibe group (4.2 [3.7-5.4] vs. 5.4 [4.7-5.9], P = .006). We concluded that ezetimibe bridge therapy might be associated with reduction in HCV VL while waiting for DAA initiation in HCV+ to HCV negative KT recipients.
Assuntos
Hepatite C Crônica , Hepatite C , Transplante de Rim , Antivirais/uso terapêutico , Ezetimiba/uso terapêutico , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Rim , Transplante de Rim/efeitos adversos , RNA , Estudos Retrospectivos , Doadores de Tecidos , TransplantadosRESUMO
RATIONALE & OBJECTIVE: Transplant centers in the United States are increasingly willing to transplant kidneys from hepatitis C virus (HCV)-infected (HCV+) donors into HCV- recipients. We studied the association between donor HCV infection status and kidney allograft function and posttransplantation allograft biopsy findings. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: We examined 65 HCV- recipients who received a kidney from a HCV+ donor and 59 HCV- recipients who received a kidney from a HCV- donor during 2018 at a single transplant center. EXPOSURE: Predictor(s) of donor infection with HCV. OUTCOMES: Kidney allograft function and allograft biopsy findings during the first year following transplantation. ANALYTICAL APPROACH: We compared estimated glomerular filtration rate (eGFR), findings on for-cause and surveillance protocol biopsies, development of de novo donor-specific antibodies (DSAs), and patient and allograft outcomes during the first year following transplantation between recipients of HCV+ and HCV- kidneys. We used linear regression to estimate the independent association between allograft function and HCV viremic status of the kidney donor. RESULTS: The mean age of recipients was 52 ± 11 (SD) years, 43% were female, 19% and 80% of recipients were White and Black, respectively. Baseline characteristics were similar between the HCV+ and HCV- groups. There were no statistically significant differences between the HCV+ and HCV- groups in delayed graft function rates (12% vs 8%, respectively); eGFRs at 3, 6, 9, and 12 months post-transplantation; proportions of patients with cellular rejection (6% vs 7%, respectively); and proportions with antibody-mediated rejection (7% vs 10%, respectively) or de novo DSAs (31% vs 20%, respectively). HCV viremic status was not associated with eGFR at 3, 6, 9, or 12 months. LIMITATIONS: Generalizability from a single-center study and small sample size was limited. CONCLUSIONS: Recipients of kidneys from donors infected with HCV had similar kidney allograft function and probability of rejection in the first year after transplantation compared to those who received kidneys from donors without HCV infection.
Assuntos
Função Retardada do Enxerto/epidemiologia , Taxa de Filtração Glomerular , Rejeição de Enxerto/epidemiologia , Hepatite C Crônica/transmissão , Falência Renal Crônica/cirurgia , Transplante de Rim , Adulto , Aloenxertos/patologia , Anticorpos/imunologia , Antivirais/uso terapêutico , Estudos de Coortes , Feminino , Rejeição de Enxerto/prevenção & controle , Hepatite C Crônica/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Modelos Lineares , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Estudos Retrospectivos , Doadores de TecidosRESUMO
The kidney donor profile index (KDPI) defines an hepatitis C (HCV) positive donor based on HCV antibody (Ab) and/or nucleic acid amplification test (NAT) positivity, with donors who are not actively infected (Ab+/NAT-) also classified as HCV positive. From Scientific Registry of Transplant Recipients dataset, we identified HCV-negative recipients, who received a kidney transplant from HCV Ab+/NAT- (n = 116) and HCV Ab-/NAT- (n = 25 574) donor kidneys. We then compared recipients' estimated glomerular filtration rate (eGFR) at 6 months in matched cohorts, using combined exact matching (based on KDPI) and propensity score matching. We created two separate matched cohorts: for the first cohort, we used the allocation KDPI, while for the second cohort we used an optimal KDPI, where the HCV component of KDPI was considered negative in Ab+/NAT- patients. The mean ± SD age of the allocation KDPI-matched cohort at baseline was 59 ± 10 years, 69% were male, 61% were white. Recipients' eGFR at 6 months after transplantation was significantly higher in the HCV Ab+/NAT- group compared to the HCV Ab-/NAT- group (61.1 ± 17.9 vs. 55.6 ± 18.8 ml/min/1.73 m2 , P = 0.011) in the allocation KDPI-matched cohort, while it was similar (61.8 ± 19.5 vs. 62.1 ± 20.1 ml/min/1.73 m2 , P = 0.9) in the optimal KDPI-matched cohort. Recipients who received HCV Ab positive, but NAT-negative donor kidneys did not experience worse 6-month eGFR than correctly matched HCV Ab-/NAT- recipients.
Assuntos
Hepatite C , Transplante de Rim , Idoso , Estudos de Coortes , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doadores de TecidosRESUMO
Our aim was to evaluate the safety of transplanting kidneys from HCV-infected donors in HCV-uninfected recipients. Data collected from 53 recipients in a single center, observational study included donor and recipient characteristics, liver and kidney graft function, new infections and de novo donor-specific antibodies and renal histology. Treatment with a direct-acting antiviral regimen was initiated when HCV RNA was detected. The mean ± SD age of recipients was 53 ± 11 years, 34% were female, 19% and 79% of recipients were white and African American, respectively. The median and interquartile range (IQR) time between transplant and treatment initiation was 76 (IQR: 68-88) days. All 53 recipients became viremic (genotype: 1a [N = 34], 1b [N = 1], 2 [N = 3], and 3 [N = 15]). The majority (81%) of recipients did not experience clinically significant increases (>3 times higher than upper limit of the normal value) in aminotransferase levels and their HCV RNA levels were in the 5 to 6 log range. One patient developed fibrosing cholestatic hepatitis with complete resolution. All recipients completed antiviral treatment and 100% were HCV RNA-negative and achieved 12-week sustained virologic response. The estimated GFRs at end of treatment and 12-week posttreatment were 67 ± 21 mL/min/1.73 m2 and 67 ± 17 mL/min/1.73 m2 , respectively. Four recipients developed acute rejection. Kidney transplantation from HCV-infected donors to HCV-negative recipients should be considered in all eligible patients.