Transplantation of organs from hepatitis C virus (HCV)-antibody (Ab) and -nucleic acid test (NAT) positive donors into HCV-negative recipients has been proposed to expand the donor pool and shorten waiting times. Data on early single-center outcomes are lacking. Nineteen liver (LT, including seven simultaneous liver-kidney [SLKT]) and 17 kidney transplant (KT) recipients received organs from HCV (+) donors; of these, 13 were HCV NAT (+) in each group. All patients who received organs from HCV NAT (+) donors developed HCV viremia post-transplant except for 2 KT recipients. Patients were treated with a variety of direct-acting antiviral regimens, with high rates of sustained virologic response among those with at least 12 weeks of follow-up past the end of treatment: 12/13 (92%) and 8/8 (100%) among LT/SLKT, and KT recipients. Median time to treatment start was 42 days (interquartile range[IQR] 35-118 days) and 40 days (IQR 26-73) post-LT/SLKT and KT, respectively. One death occurred in a SLKT recipient unrelated to HCV or its treatment. There was no significant increase in rejection, proteinuria, or changes in immunosuppression in any group. Organs from HCV-viremic donors can be utilized for HCV-uninfected recipients with good short-term outcomes. K E Y W O R D Shepatitis C virus, hepatitis C-positive donors, kidney transplantation, liver transplantation 2 of 11 | CRISMALE Et AL. unacceptable due to the low efficacy and high risks associated with IFN-based therapy post-transplantation. Such organs were therefore reserved for transplantation into those already with HCV infection. Even among these patients, the persistence of HCV infection post-transplantation was associated with poor outcomes and led to worse post-transplant survival. 4,5 However, the advent of highly effective direct-acting antiviral therapy (DAAs) has led to post-transplantation HCV cure rates exceeding 95%, and with it, a negation of the ill effects of HCV previously seen in both LT and KT recipients. 6,7 A number of clinical trials, along with data from the HCV-TARGET cohort, have demonstrated the efficacy and safety of the use of these agents in the post-transplant setting. 8,9 In the HCV-TARGET cohort, adverse events leading to treatment discontinuation were uncommon, affecting only 1.6%. 8 Newer agents, including glecaprevir/ pibrentasvir (GLE/PIB), have similarly been shown to be safe and efficacious. 10 Indeed, recently published data derived from the Scientific Registry of Transplant Recipients (SRTR) suggest equivalent 1-and3-year survival among HCV-infected patients undergoing LT. 6 In the United States, the potential pool of HCV-positive organs is growing, largely due to a rising incidence of HCV in persons who inject drugs. There is significant geographic and demographic overlap between the opioid epidemic and incident HCV infection. 11 Data suggest that up to 52% of HCV-infected individuals are concentrated in 9 US states, the majority of which have a significant burden of patients suffering with opioid addiction. 12 Drug overdose...
The influence of patient characteristics and immunosuppression management on COVID-19 outcomes in kidney transplant recipients (KTRs) remains uncertain. We performed a single-center, retrospective review of all adult KTRs admitted to the hospital with confirmed COVID-19 between 03/15/2020 and 05/15/2020. Patients were followed from the date of admission up to 1 month following hospital discharge or study conclusion (06/15/2020). Baseline characteristics, laboratory parameters, and immunosuppression were compared between survivors and patients who died to identify predictors of mortality. 38 KTRs with a mean baseline eGFR of 52.5 ml/ min/1.73 m 2 were hospitalized during the review period. Maintenance immunosuppression included tacrolimus (84.2%), mycophenolate (89.5%), and corticosteroids (81.6%) in the majority of patients. Eleven patients (28.9%) died during the hospitalization. Older age (OR = 2.05; 1.04-4.04), peak D-dimer (OR = 1.20; 1.04-1.39), and peak white blood cell count (OR = 1.11; 1.02-1.21) were all associated with mortality among KTRs hospitalized for COVID-19. Increased mortality was also observed among KTRs with concomitant HIV infection (87.5% vs. 36.1%; p < .01). Conversely, immunosuppression intensity and degree of reduction following COVID-19 diagnosis were not associated with either survival or acute allograft rejection. Our findings potentially support a strategy of individualization of immunosuppression targets based on patient-specific risk factors, rather than universal immunosuppression reduction for KTRs at risk from COVID-19.
Limited data exist on the effect of IVIg on anti-HLA antibodies as determined by solid phase assays. We reviewed our experience treating sensitized waitlisted kidney transplant recipients with IVIg as a method for desensitization and report our results utilizing Luminex single antigen (LSA) bead assay to quantify antibody reactivity (MFI). Fifteen patients with a cPRA>40% received 2 g/kg IVIg per month for 4 months or until transplanted. LSA testing was done before and after IVIg. Median MFI for anti-class I antibodies fell in 11 (73%), and increased in 4 (27%) patients after IVIg. Similar significant changes in MFI for anti-class II antibodies were observed in 10 patients (66%). Administration of IVIg was associated with a modest decrease in reactivity to both class I and II HLA antigens (median MFI change 493 and 1110 respectively; p<0.0001) but did not significantly alter mean cPRA (85% before IVIg vs. 80% after IVIg; p=0.1). Our data suggest a smaller effect of IVIg on HLA antibody reactivity than previously described, leading us to question how best to measure the efficacy of a desensitization protocol in current practice.
Belatacept is a non-nephrotoxic immunosuppressive agent, which may make it the ideal agent for patients with delayed or slow graft function on calcineurin inhibitors. There are limited data on conversion of patients to belatacept within 6 months of transplantation. Between January 2012 and December 2015, 16 patients were converted to belatacept for delayed or poor graft function (eGFR<30 mL/min/1.73 m , MDRD); three were HIV positive. Conversion protocols were analyzed in patients ≤4 months and 4-6 months post-transplantation. Mean serum creatinine levels after belatacept conversion were compared with preconversion levels. Patient survival was 100%, and graft survival was 88%. The mean creatinine fell from 3.9±1.82 mg/dL prebelatacept conversion to 2.1±1.1 mg/dL at 6 months and 1.9±0.47 mg/dL (median 1.8 mg/dL) at 12 months postconversion. There was no significant increased risk of rejection, infection, or malignancy. HIV parameters remained largely stable. Early conversion to belatacept in patients with DGF or slow graft function is safe and efficacious, in a single-center nonrandomized retrospective analysis.
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