Allograft transmission of hepatitis C virus infection from infected donors in cardiac transplantation

BACKGROUND: The frequency and outcome of hepatitis C virus (HCV) infection in recipients of hearts from HCV-infected donors remains poorly characterized. METHODS: Between 1991 and 1999, 10 anti-HCV-negative patients received hearts from donors who were anti-HCV and HCV RNA-positive. Each recipient was tested for anti-HCV and HCV RNA and serially evaluated for liver dysfunction. Recipient records were reviewed for cumulative steroid boluses in the first posttransplant year and other components of the immune suppression regimen. We analyzed recipient outcome in relation to the virologic status of the donor, including the level of HCV RNA and genotype and the type of antirejection therapy. RESULTS: All 10 recipients became HCV RNA positive. Donor-recipient pairs expressed identical genotypes in each instance. Six of nine evaluable recipients developed biochemical evidence of hepatitis. Recipients with genotype 1 (1a, 1b) accounted for five of the six cases, and all patients with genotype 1 developed hepatitis. Severe liver injury occurred in two patients. Two deaths occurred, both of which were genotype 1 patients who had been given multiple boluses of corticosteroids in the first posttransplant year. No definite relationship between viral load in the donor and recipient outcome was found. CONCLUSION: Transmission of HCV infection from cardiac donors who are viremic at the time of organ donation occurs with high frequency and can cause severe hepatitis. Hearts from infected patients should probably be restricted to those recipients who already have evidence for hepatitis C or are in need of emergent transplantation.     

Center‐level trends in utilization of HCV‐exposed donors for HCV‐uninfected kidney and liver transplant recipients in the United States

Several single‐center reports of using HCV‐viremic organs for HCV‐uninfected (HCV‐) recipients were recently published. We sought to characterize national utilization of HCV‐exposed donors for HCV‐ recipients (HCV D+/R?) in kidney transplantation (KT) and liver transplantation (LT). Using SRTR data (April 1, 2015‐December 2, 2018) and Gini coefficients, we studied center‐level clustering of 1193 HCV D+/R? KTs and LTs. HCV‐viremic (NAT+) D+/R? KTs increased from 1/month in 2015 to 22/month in 2018 (LTs: 0/month to 12/month). HCV‐aviremic (Ab+/NAT‐) D+/R? KTs increased from < 1/month in 2015 to 26/month in 2018 (LTs: <1/month to 8/month). HCV‐ recipients of viremic and aviremic kidneys spent a median (interquartile range [IQR]) of 0.7 (0.2‐1.6) and 1.6 (0.4‐3.5) years on the waitlist versus 1.8 (0.5‐4.0) among HCV D?/R?. HCV‐ recipients of viremic and aviremic livers had median (IQR) MELD scores of 24 (21‐30) and 25 (21‐32) at transplantation versus 29 (23‐36) among HCV D?/R?. 12 KT and 14 LT centers performed 81% and 76% of all viremic HCV D+/R? transplants; 11 KT and 13 LT centers performed 76% and 69% of all aviremic HCV D+/R? transplants. There have been marked increases in HCV D+/R? transplantation, although few centers are driving this practice; centers should continue to weigh the risks and benefits of HCV D+/R? transplantation.     

Hepatitis C–associated focal proliferative glomerulonephritis in an aviremic recipient of a hepatitis C–positive antibody donor liver

Shortage of organs for liver transplantation (LT) and the availability of highly efficient pan-genotypic direct-acting antivirals (DAAs) against hepatitis C virus (HCV) have allowed the use of livers from HCV-positive antibody/negative nucleic acid test donors (dHCV Ab+/NAT−) into aviremic HCV recipients over the last few years. We report the case of a patient who received an LT from an HCV Ab+/NAT− donor and, after HCV viremic conversion, developed a nephrotic syndrome due to a focal proliferative glomerulonephritis early after LT. Patient's renal function and proteinuria resolved after successful treatment with DAAs. Renal and hepatic function remain normal over 24 months of follow-up. This case restates the success of LT using livers from dHCV Ab+/NAT− in aviremic recipients in the context of DAAs while illustrating the risk for potential complications associated with the HCV transmission and reinforcing the importance of early initiation of anti-HCV therapy.     

Accepting hepatitis C virus–infected donor hearts for transplantation: Multistep consent,unrealized opportunity,and the Stanford experience

The current mismatch between supply and demand of organs has prompted transplant clinicians to consider innovative solutions to broaden the donor pool. Advancements of direct‐acting antiviral agent (DAA) therapy for hepatitis C virus (HCV) have allowed entertaining the use of viremic donor organs in nonviremic recipients. In this report, we describe the evolution of HCV treatment, ethics and informed consent, cost‐effectiveness of HCV medications in treating acute HCV post‐transplantation, and the Stanford experience with two HCV‐viremic donor heart transplantations. We describe excellent short‐term outcomes post–heart transplantation with HCV NAT‐positive organs. The availability of this therapy may expand the donor pool. While we await larger‐scale clinical data on the effectiveness and safety of DAA therapy in patients after heart transplantation, many transplant centers have already started accepting organs from HCV‐infected donors, balancing the unknown long‐term risks versus the benefits of shorter wait times and expansion of the donor pool. Protocols and multidisciplinary teams are needed to effectively communicate risk to potential recipients, to ensure timely DAA access, and to implement appropriate clinical follow‐up in order to achieve excellent clinical outcomes and to maximize the donor pool by utilizing HCV‐infected organs for heart transplantation.     

Are we underestimating the quality of aviremic hepatitis C–positive kidneys? Time to reconsider

Kidney Donor Risk Index (KDRI) introduced in 2009 included hepatitis C serologic but not viremic status of the donors. With nucleic acid amplification testing (NAT) now being mandatory, further evaluation of these donors is possible. We conducted a retrospective matched case‐control analysis of adult deceased donor kidney transplants performed between December 5, 2014 to December 31, 2016 with the KDRI score and hepatitis C virus antibody (HCV Ab) and NAT testing status obtained from the United Network for Organ Sharing database. The 205 aviremic HCV Ab+ NAT ‐ kidney transplants were compared to KDRI matched control kidneys that were HCV Ab–NAT‐. The aviremic HCV kidneys were recovered from donors who were significantly younger, more likely to be white, and less likely to have hypertension and diabetes. The majority of the recipients of the aviremic HCV kidneys when compared to matched controls were HCV positive: 90.2% vs 4.3%. The recipients were significantly older, were on dialysis for a shorter time, and were transplanted sooner. The graft survival of aviremic HCV kidneys was similar (P < .08). If the HCV status of the aviremic kidneys was assumed to be negative, 122 more kidneys could have been allocated to patients with estimated posttransplant survival <20. Seven kidneys would no longer have Kidney Donor Profile Index >85%. Further policies might consider these findings to appropriately allocate these kidneys.     

Donor‐derived infections: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation will review the current state of the art of donor‐derived infections. Specifically, the guideline will summarize standardized definitions and approaches to defining imputability, updated data on the epidemiology of donor‐derived infections, and approaches to risk mitigation against transmission of infections. This update will additionally provide guidance on the use of HIV+ donors in HIV+ recipients, the use of HCV‐viremic donors in non‐viremic recipients, donors with endemic infections, and donors with bacteremia, meningitis, and encephalitis. Lastly, the guidance will summarize an approach to recipients with a suspected donor‐derived infection.     

Immediate administration of antiviral therapy after transplantation of hepatitis C‐infected livers into uninfected recipients: Implications for therapeutic planning

The practice of transplanting hepatitis C (HCV)‐infected livers into HCV‐uninfected recipients has not previously been recommended in transplant guidelines, in part because of concerns over uncontrolled HCV infection of the allograft. Direct‐acting antivirals (DAAs) provide an opportunity to treat donor‐derived HCV‐infection and should be administered early in the posttransplant period. However, evidence on the safety and efficacy of an immediate DAA treatment approach, including how to manage logistical barriers surrounding timely DAA procurement, are required prior to broader use of HCV‐positive donor organs. We report the results of a trial in which 14 HCV‐negative patients underwent successful liver transplantation from HCV‐positive donors. Nine patients received viremic (nucleic acid testing [NAT]‐positive) livers and started a 12‐week course of oral glecaprevir‐pibrentasvir within 5 days of transplant. Five patients received livers from HCV antibody‐positive nonviremic donors and were followed using a reactive approach. Survival in NAT‐positive recipients is 100% at a median follow‐up of 46 weeks. An immediate treatment approach for HCV NAT‐positive liver transplantation into uninfected recipients is safe and efficacious. Securing payer approval for DAAs early in the posttransplant course could enable need‐based allocation of HCV‐positive donor organs irrespective of candidate HCV status, while averting chronic HCV allograft infection.     

ABO血型基因与移植肾急性排斥反应相关性的研究

目的 探讨ABO血型基因与移植肾急性排斥反应(AR)的相关性.方法 采用引物特异性聚合酶链式反应(PCR-SSP)技术检测2009年5月至2010年2月87例肾移植受者及其对应的48例供者ABO(A1、A2、B、O1、O2)血型基因,分析供受者ABO血型基因相合组与错配组受者AR发生、治疗及转归情况.结果 PCR-SSP测定ABO血型基因推定的表型和血清学方法测定ABO血型表型完全相符.供受者ABO血型基因相合组受者50例,发生AR 6例,经甲泼尼龙(MP)冲击治疗后临床逆转.ABO血型基因错配组受者37例,发生AR 11例,经MP冲击治疗后,临床逆转10例,周期性反复发生AR 1例.错配组与相合组受者AR发生率差异有统计学意义(29.7%与12.0%,P<0.05).错配组1例A2O1血型基因受者接受A1O1血型基因供肾后,受者血清检测发现抗A1抗体,抗体效价IgG 1:64,IgM 1:16,移植术后3～10个月周期性反复发生AR,且周期逐渐变短,激素疗效逐渐降低,术后1年SCr达441μmol/L.结论 检测供受者HLA时同步检测ABO血型基因具有很强的可行性.A2血型基因受者适宜选择O型供肾.供受者ABO血型基因错配是介导肾移植术后AR的危险因素,检测供受者ABO血型基因,降低ABO血型基因错配率对预防AR有一定的临床意义.     

The effect of pulsatile pump perfusion on hepatitis C transmission in kidney transplantation: A prospective pilot study

With increasing utilization of hepatitis C (HCV) viremic donor organs, there may be a role for kidney pump perfusion to reduce viral load and prevent HCV transmission. We performed a prospective pilot study of HCV viremic donors; one kidney from each donor pair was pumped with perfusate exchanges and viral load testing at least every 4 hours. Donor, recipient, and transplant characteristics were obtained with clinical outcomes. Linear regression was performed to quantify the association between pump time and perfusate viral load. Six HCV viremic donors for six pairs of aviremic recipients were included. Perfusate of the pumped kidneys showed detectable virus throughout the pump cycles. Although perfusate viral levels decreased with increasing pump times, this was not statistically significant (β = −.48, P = .36). All recipients had detectable HCV RNA postoperatively. The pumped cohort had an insignificantly reduced mean viral load compared to pumped recipients (1352 ± 2006 vs 26 170 ± 61 211, P = .09). Time to initiation of direct-acting antiviral was 32 ± 12 vs 26 ± 7 days (P = .17) and to undetectable levels was 66 ± 27 vs 55 ± 22 days (P = .82) for the pumped and unpumped cohorts, respectively. Pulsatile perfusion alone does not appear adequate to decrease HCV transmission. Future studies will need to explore additional ex vivo interventions to pumping.     

Viremia and excretion of TT virus in immunosuppressed heart transplant recipients and in immunocompetent individuals

BACKGROUND: The TT virus (TTV) was discovered in patients with symptomatic posttransfusion hepatitis, but many viremic individuals are asymptomatic. Inadvertent transfusion-associated transmission must therefore be anticipated. We screened blood donors and heart transplant recipients for TTV infections. METHODS: Nested polymerase chain reaction was used to detect TTV DNA in plasma, serum, urine, and fecal samples from 600 blood donors, from 100 healthy individuals, and from 495 heart transplant recipients. RESULTS: A total of 3.2% of the blood donors, but 25% of the heart transplant recipients were viremic. TTV subtypes G1a/b and G2a/b were observed in both groups, but the subtype distributions were discrepant. A severe, acute infection with TTV subtype 3 was observed in one blood donor. The prevalence of TTV infections in heart transplant recipients was not correlated to transfusion frequency. Nine viremic heart transplant recipients and their 75 blood donors were studied in detail. Seven blood donors were viremic, but only two "pairs" of viremic blood donors and transfusion recipients had identical TTV isolates. TTV DNA was detected in the feces of 5% (5/100) of immunocompetent individuals (staff), in 46% (52/112) of viremic heart transplant recipients, and in the urine of 55% (20/36). TTV DNA was detected in six of six batches of pooled "virus-inactivated" plasma (solvent/detergent treated), and in none of eight batches of commercial immunoglobulins. CONCLUSION: Although TTV is transfusion-transmissible, the parenteral transmission rate may have been overestimated. Many TTV infections are apparently acquired by nonparenteral routes. Immunoglobulins are safe but pooled plasma is not safe regarding TTV transmission.     

Liver transplantation for hepatitis C virus (HCV) non‐viremic recipients with HCV viremic donors

In the context of organ shortage, the opioid epidemic, and effective direct‐acting antiviral (DAA) therapy for hepatitis C virus (HCV), more HCV‐infected donor organs may be used for liver transplantation. Current data regarding outcomes after donor‐derived HCV in previously non‐viremic liver transplant recipients are limited. Clinical data for adult liver transplant recipients with donor‐derived HCV infection from March 2017 to January 2018 at our institution were extracted from the medical record. Ten patients received livers from donors known to be infected with HCV based on positive nucleic acid testing. Seven had a prior diagnosis of HCV and were treated before liver transplantation. All recipients were non‐viremic at the time of transplantation. All 10 recipients derived hepatitis C infection from their donor and achieved sustained virologic response at 12 weeks posttreatment with DAA‐based regimens, with a median time from transplant to treatment initiation of 43 days (IQR 20–59). There have been no instances of graft loss or death, with median follow‐up of 380 days (IQR 263–434) posttransplant. Transplantation of HCV‐viremic livers into non‐viremic recipients results in acceptable short‐term outcomes. Such strategies may be used to expand the donor pool and increase access to liver transplantation.     

Transplantation of kidneys from HCV-positive donors: a safe strategy?

Hepatitis C Virus (HCV) infection is the most important cause of liver disease after renal transplantation (RT). The impact of HCV on patient and graft survival after RT remains controversial; however, the great majority of studies with large size and adequate follow-up have shown the detrimental impact of HCV on long-term patient and graft survival after RT. The use of kidneys from anti-HCV positive donors could help decrease the continuing disparity between the number of patients on the transplant waiting list and the number of patients receiving a transplant each year. Single-center experiences have suggested transplanting kidneys from anti-HCV positive donors only in anti-HCV positive dialysis patients. Such practice has not demonstrated any adverse effect on the short-term patient survival; the waiting times for RT were shortened. A better alternative seems to be a policy of transplanting kidneys from anti-HCV positive donors only in HCV RNA positive recipients. This requires HCV RNA testing of all anti-HCV positive dialysis patients awaiting RT. Matching donors and recipients for HCV genotype has been suggested; however, the assessment of donor HCV genotype is currently hampered by time constraints. Recent evidence based on large data base demonstrated that RT recipients of HCV-positive donors are at independent increased risk of mortality; unadjusted 3-year patient survival was 85% versus 93% (P=0.01) in all recipients of donor HCV-positive and HCV-negative kidneys, respectively. This was observed in all recipient subgroups including elderly and HCV-positive recipients. In the near future, rapid nucleic acid testing (NAT) of donors and recipients will allow the assessment of the HCV viremic status in order to maximize organ use. With appropriate informed consent, use of a renal graft from an HCV positive donor may be offered to an HCV infected recipient. Additional studies are needed to clarify the link between donor HCV-positive kidneys and patient mortality.     

Risk of advanced fibrosis with grafts from hepatitis C antibody-positive donors: a multicenter cohort study

Over the last decade, the use of liver grafts from hepatitis C virus antibody-positive donors [HCV(+)Ds] has tripled in the United States. Although previous studies have demonstrated no association between an HCV(+)D status and graft loss, the effects of an HCV(+)D on histological outcomes are not well known. Hepatitis C virus (HCV)-infected recipients at 5 US centers (2002-2007) who survived more than 30 days with 1 or more posttransplant biopsy samples were included. Cox regression was used to examine the association between an HCV(+)D status and advanced fibrosis (stage 3/4 or higher). Ninety-nine of the 1206 patients (8%) received an HCV(+)D graft. Recipients of HCV(+)D grafts were older than recipients of hepatitis C virus antibody-negative donor [HCV(-)D] grafts (P = 0.03), but they were otherwise similar. HCV(+)D grafts were significantly lower in quality according to the donor risk index (P < 0.001). Advanced fibrosis occurred in 32% of HCV(+)D graft recipients and in 28% of HCV(-)D graft recipients (P = 0.39). The unadjusted 1- and 3-year rates of advanced fibrosis were significantly higher for HCV(+)D graft recipients (14% and 48%) versus HCV(-)D graft recipients (7% and 33%, P = 0.01). Transplantation with HCV(+)D grafts was associated with a 58% increased risk of advanced fibrosis [95% confidence interval (CI) = 1.05-2.36, P = 0.03]. However, in an analysis stratified by the mean donor age of 45 years, an HCV(+)D status was associated with advanced fibrosis only with donors >45 years old [hazard ratio (HR) = 1.76, 95% CI = 1.06-2.93, P = 0.03] and not with donors ≤45 years old (HR = 0.94, 95% CI = 0.47-1.87, P = 0.85). In conclusion, a careful consideration of the risks and benefits is needed with HCV(+)D grafts. Recipients of HCV(+)D grafts (especially from older donors) should undergo close monitoring for more rapidly progressive fibrosis. Studies are needed to determine whether early HCV therapy modifies this risk.     

Process of selecting and educating HCV‐uninfected kidney waiting‐list candidates for HCV‐infected kidney transplantation

Long waiting times for kidney transplant (KT) and the high risk of mortality on dialysis have prompted investigation into strategies to utilize hepatitis C virus (HCV)‐infected organs to decrease discard rates of potentially viable kidneys. Due the opioid epidemic, the number of HCV‐infected donors has increased significantly. With the development of direct‐acting antiviral therapies for HCV infection, now more than 95% of patients who received treatment are cured. Experimental trials have used direct‐acting antiviral therapy to treat HCV infection in HCV‐uninfected transplant recipients of kidneys from HCV‐viremic donors. To date, HCV has been eradicated in all cases. Though these strategies will potentially increase the donor pool of available kidneys, shorten waitlist times, and ultimately decrease mortality in patients waiting for KT, identifying the ideal candidates and educating them about a protocol to utilize direct‐acting antiviral therapy to cure HCV after it is transmitted is essential. We present our approach to patient selection and education for a clinical trial in transplantation of HCV viremic kidneys into uninfected recipients.     

Short‐term outcomes of deceased donor renal transplants of HCV uninfected recipients from HCV seropositive nonviremic donors and viremic donors in the era of direct‐acting antivirals

The United States opioid use epidemic over the past decade has coincided with an increase in hepatitis C virus  (HCV) positive donors. Using propensity score matching, and the Organ Procurement Transplant Network data files from January 2015 to June 2019, we analyzed the short‐term outcomes of adult deceased donor kidney transplants of HCV uninfected recipients with two distinct groups of HCV positive donors (HCV seropositive, nonviremic n = 352 and viremic n = 196) compared to those performed using HCV uninfected donors (n = 36 934). Compared to the reference group, the transplants performed using HCV seropositive, nonviremic and viremic donors experienced a lower proportion of delayed graft function (35.2 vs 18.9%; P < .001 [HCV seropositive, nonviremic donors] and 36.2 vs 16.8% ;  P < .001[HCV viremic donors]). The recipients of HCV viremic donors had better allograft function at 6 months posttransplant (eGFR [54.1 vs 68.3 mL/min/1.73 m2; P = .004]. Furthermore, there was no statistical difference in the overall graft failure risk at 12 months posttransplant by propensity score matched multivariable Cox proportional analysis (HR =  0.60, 95% CI  0.23 to  1.29 [HCV seropositive, nonviremic donors] and HR =  0.85, 95% CI 0.25 to  2.96 [HCV viremic donors]). Further studies are required to determine the long‐term outcomes of these transplants and address unanswered questions regarding the use of HCV viremic donors.     

Transplantation of kidneys from hepatitis C–infected donors to hepatitis C–negative recipients: Single center experience

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.     

Underutilization of Hepatitis C‐Positive Kidneys for Hepatitis C‐Positive Recipients

Hepatitis C‐positive (HCV(+)) candidates likely derive survival benefit from transplantation with HCV(+) kidneys, yet evidence remains inconclusive. We hypothesized that lack of good survival benefit data has led to wide practice variation. Our goal was to characterize national utilization of HCV(+) kidneys for HCV(+) recipients, and to quantify the risks/benefits of this practice. Of 93,825 deceased donors between 1995 and 2009, HCV(+) kidneys were 2.60‐times more likely to be discarded (p < 0.001). However, of 6830 HCV(+) recipients, only 29% received HCV(+) kidneys. Patients over 60 relative rate (RR 0.86), women (RR 0.73) and highly sensitized patients (RR 0.42) were less likely to receive HCV(+) kidneys, while African Americans (RR 1.56), diabetics (RR 1.29) and those at centers with long waiting times (RR 1.19) were more likely to receive them. HCV(+) recipients of HCV(+) kidneys waited 310 days less than the average waiting time at their center, and 395 days less than their counterparts at the same center who waited for HCV(?) kidneys, likely offsetting the slightly higher patient (HR 1.29) and graft loss (HR 1.18) associated with HCV(+) kidneys. A better understanding of the risks and benefits of transplanting HCV(+) recipients with HCV(+) kidneys will hopefully improve utilization of these kidneys in an evidence‐based manner.     

Use of hepatitis C virus-positive grafts in liver transplantation: a single-centre experience

AIM: Our goal was to evaluate the outcome of HCV(+) recipients after liver transplantation (LT) using HCV(+) donors and the interaction between donor and recipient viral strain. METHODS: We performed a retrospective analysis of 21 LT performed between 1998 and 2004 using livers from HCV(+) donors in HCV(+) recipients. Two hundred thirty-seven patients with HCV cirrhosis who underwent LT with livers from HCV(-) donors were the control group. Ishak score (IS) was evaluated for all HCV(+) grafts. The considered variables included donor age, hepatic enzymes, intensive care unit stay, HCV genotype, ischemia time, recipient age, UNOS status, Child score, HCV genotype (before and 6 months after LT) and IS (after LT). We analyzed patient, graft, and disease-free survival. RESULTS: HCV(+) donors were significantly older than HCV(-) donors. The cumulative 5-year patient and graft survivals and disease free intervals were not different between groups. IS grading was more than 2/18 in two cases; the only graft with a staging score over 2/6 was retransplanted for early nonfunction. In two cases, different HCV genotypes were matched and donor strain took over the recipient strain. In one patient, donor genotyping 2a-2c took over recipient genotyping 1b and 9 months after LT recurrent hepatitis was documented, but antiviral therapy cleared HCV. CONCLUSIONS: Livers from HCV(+) donors can safely be used in HCV(+) recipients. Hepatic biopsy must always be performed; livers with bridging fibrosis should not be used. The takeover of one strain by another may change the prognosis of the patient if the predominant strain is more sensitive to antiviral therapy.     

Deliberate donor-specific blood transfusions prior to living related renal transplantation. A new approach.

In order to select MLC incompatible one-haplotype related donor-recipient pairs that would achieve better graft survival and in an effort to alter the recipient immune response, 45 patients received three fresh blood transfuions from their prospective kidney donors. Recipient sensitization was evaluated by cross-match testing weekly sera obtained during and after the blood transfusions against donor T- and B-lymphocytes at 5 C (cold) and 37 C (warm). Thirteen (29%) of the 45 potential related recipients developed a positive warm T-cell cross-match or a persistent warm B-cell cross-match to their blood donor and related transplantation was not performed. Thirty-two (71%) patients had an appropriate negative cross-match to their blood donor. Thirty of these patients subsequently received kidneys from their blood donor. Ninety-seven per cent of the kidneys are functioning from one to 25 months with a single graft failure due to a patient discontinuing immunosuppressive medication. In addition to the excellent graft survival there was an unusually low incidence of rejection episodes in the recipients of kidneys from their blood donor so that the posttransplant course paralleled that of HLA-identical siblings. This approach may have future application with two-haplotype mismatched donor-recipient pairs, both related and unrelated.     

Pancreas transplantation from hepatitis C viremic donors to uninfected recipients

Despite utilization of hepatitis C viremic organs for hepatitis C naïve recipients (HCV D+/R-) in other solid organ transplants, HCV viremic pancreata remain an unexplored source of donor organs. This study reports the first series of HCV D+/R- pancreas transplants. HCV D+/R- had shorter waitlist times compared to HCV D-/R-, waiting a mean of 16 days from listing for HCV-positive organs. HCV D+/R- had a lower match allocation sequence than HCV D-/R-, and this correlated with receipt of organs with a lower Pancreas Donor Risk Index (PDRI) score. All HCV D+/R- had excellent graft function with a mean follow-up of 438 days and had undetectable HCV RNA levels by a mean of 23 days after initiation of HCV-directed therapy. The rates of infectious complications, reoperation, readmission, rejection, and length of stay were not impacted by donor HCV status. A national review of potential ideal pancreas donors found that 37% of ideal HCV-negative pancreas allografts were transplanted, compared to only 5% of ideal HCV-positive pancreas allografts. The results of the current study demonstrate the safety of accepting HCV-positive pancreata for HCV-naïve recipients and advocates for increased utilization of ideal HCV-positive pancreas allografts.