Utilization of hepatitis B virus-positive allografts in liver transplantation: a new arrow to the bowstring for expanding the donor pool?
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ABSTRACT:
SUBMITTER: Xu G
PROVIDER: S-EPMC9023818 | biostudies-literature | 2022 Apr
REPOSITORIES: biostudies-literature
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Utilization of hepatitis B virus-positive allografts in liver transplantation: a new arrow to the bowstring for expanding the donor pool?
Xu Gang G Jiang Chen-Hao CH Xiao Yao Y Lyu Tao T Jiang Li L Yan Lyu-Nan LN Yang Jia-Yin JY
Hepatobiliary surgery and nutrition 20220401 2
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Project description:ImportanceIncreased utilization of hepatitis C virus (HCV)-positive liver allografts for liver transplant (LT) has been endorsed as one of several ways to combat national organ shortages. However, HCV-positive donors remain poorly characterized, and Organ Procurement and Transplantation Network regional differences in the utilization of HCV-positive liver allografts are unclear.ObjectiveTo characterize HCV-positive donors and the allografts that come from them.Design, setting, and participantsIn this cross-sectional study, the Scientific Registry of Transplant Recipients database was queried for all donors who underwent HCV testing from June 2015 to December 2018. Clinical and allograft characteristics were evaluated, and utilization across the United States was studied. Patients with positive or negative results for HCV antibody (Ab) and HCV nucleic acid amplification testing (NAT) were included in this study. Donors utilized for living donor transplant and pediatric (age <18 years) recipients were excluded.Main outcomes and measuresThe primary comparison was between donors who were HCV Ab positive and those who were HCV Ab negative. Regional variations in the utilization of HCV-positive and HCV-negative donors were analyzed.ResultsOf 24 500 donors utilized for LT, 1887 (7.7%) were HCV Ab positive; 64.4% of HCV Ab-positive donors were HCV NAT positive. HCV Ab-positive donors were younger (median [interquartile range] age, 35 [29-46] years vs 40 [27-54] years) and had fewer comorbidities, such as diabetes (8.3% vs 12.0%) and hypertension (25.9% vs 35.2%), compared with HCV Ab-negative donors. These findings were even more pronounced in HCV Ab-positive /NAT-positive compared with HCV Ab-positive/NAT-negative donors. Organ Procurement and Transplantation Network regions 2, 3, 10, and 11 had the highest absolute utilization of HCV Ab-positive donors, accounting for 64.4% of all HCV Ab-positive donors used in the United States. Region 1 had the highest relative utilization of HCV Ab-positive donors (18.7%). The use of HCV Ab-positive donors in some regions was associated with the rate of drug overdose, but this was not always the case. Similar utilization results were found with HCV NAT-positive donors.Conclusions and relevanceIn this cross-sectional study, HCV-positive donors were younger and healthier than utilized HCV-negative donors. Significant differences exist in the utilization of HCV-positive donors across the 11 Organ Procurement and Transplantation Network regions, which is not entirely explained by organ demand or by higher availability of HCV-positive livers as per the distribution of the opioid epidemic. Initiatives to increase the use of HCV-positive donors, particularly in regions of high organ demand, should be implemented.
| S-EPMC7718602 | biostudies-literature
Project description:Purpose of programThe ongoing shortage of organs for transplant combined with Manitoba having the highest prevalence of end-stage renal disease (ESRD) in Canada has resulted in long wait times on the deceased donor waitlist. Therefore, the Transplant Manitoba Adult Kidney Program has ongoing quality improvement initiatives to expand the deceased donor pool. This clinical transplant protocol describes the use of prophylactic pan-genotypic direct-acting anti-viral agents (DAA) for transplanting hepatitis C (HCV)-viremic kidneys (HCV antibody positive/nucleic acid [nucleic acid amplification testing, NAT] positive) to HCV-naïve recipients as routine standard of care. We will evaluate the provincial implementation of this protocol as a prospective observational cohort study.Sources of informationScoping literature review and key stakeholder engagement with interdisciplinary health care providers and health system leaders/decision markers.MethodsPatients will be screened pre-transplant for eligibility and undergo a multilevel education and consent process to participate in this expanded donor program. Incident adult HCV-naïve recipients of an HCV-viremic kidney transplant will be treated prophylactically with glecaprevir-pibrentasvir with the first dose administered on call to the operation. Glecaprevir-pibrentasvir will be used for 8 weeks with viral monitoring and hepatology follow-up. Primary outcomes are sustained virologic response (SVR) at 12 weeks and the tolerability of DAA therapy. Secondary outcomes within the first year post-transplant are patient and graft survival, graft function, biopsy-proven rejection, HCV transmission to recipient (HCV NAT positive), and HCV nonstructural protein 5A (NS5A) resistance. Safety outcomes within the first year post-transplant include fibrosing cholestatic hepatitis, acute liver failure, primary and secondary DAA treatment failure, HCV transmission to a recipient's partner, elevated liver enzymes ≥2-fold, abnormal international normalized ratio (INR), angioedema, anaphylaxis, cirrhosis, and hepatocellular carcinoma.Key findingsThis program successfully advocated for and obtained hospital formulary, provincial Exceptional Drug Status (EDS), and Non-Insured Health Benefits (NIHB) to provide prophylactic DAA therapy for this indication, and this information may be useful to other provincial transplant organizations seeking to establish an HCV-viremic kidney transplant program with prophylactic DAA drug coverage.Limitations(1) Patient engagement was not undertaken during the program design phase, but patient-reported experience measures will be obtained for continuous quality improvement. (2) Only standard criteria donors (optimal kidney donor profile index [KDPI] ≤60) will be used. If this approach is safe and feasible, then higher KDPI donors may be included.ImplicationsThe goal of this quality improvement project is to improve access to kidney transplantation for Manitobans. This program will provide prophylactic DAA therapy for HCV-viremic kidney transplant to HCV-naïve recipients as routine standard of care outside a clinical trial protocol. We anticipate this program will be a safe and effective way to expand kidney transplantation from a previously unutilized donor pool.
| S-EPMC8317248 | biostudies-literature
Project description:Liver transplantation is the only curative option for end-stage liver disease and is necessary for an increasing number of patients with advanced primary or secondary liver cancer. Many patient groups can benefit from this treatment, however the shortage of liver grafts remains an unsolved problem. Liver bioengineering offers a promising method for expanding the donor pool through the production of acellular scaffolds that can be seeded with recipient cells. Decellularization protocols involve the removal of cells using various chemical, physical, and enzymatic steps to create a collagenous network that provides support for introduced cells and future vascular and biliary beds. However, the removal of the cells causes varying degrees of matrix damage, that can affect cell seeding and future organ performance. The main objective of this review is to present the existing techniques of producing decellularized livers, with an emphasis on the assessment and definition of acellularity. Decellularization agents are discussed, and the standard process of acellular matrix production is evaluated. We also introduce the concept of the stepwise assessment of the matrix during decellularization through decellularization cycles. This method may lead to shorter detergent exposure times and less scaffold damage. The introduction of apoptosis induction in the field of organ engineering may provide a valuable alternative to existing long perfusion protocols, which lead to significant matrix damage. A thorough understanding of the decellularization process and the action of the various factors influencing the final composition of the scaffold is essential to produce a biocompatible matrix, which can be the basis for further studies regarding recellularization and retransplantation.
| S-EPMC11762870 | biostudies-literature
Project description:BackgroundGiven the gap between patients in need of a renal transplantation (RTx) and organs available, transplantation centers increasingly accept organs of suboptimal quality, e.g. from donors with acute kidney injury (AKI).MethodsTo determine the outcome of kidney transplants from deceased donors with AKI (defined as ≥ AKIN stage 1), all 107 patients who received a RTx from donors with AKI between August 2004 and July 2014 at our center were compared to their respective consecutively transplanted patients receiving kidneys from donors without AKI. 5-year patient and graft survival, frequencies of delayed graft function (DGF), acute rejections and glomerular filtration rate (eGFR, CKD-EPI) were assessed.ResultsPatient survival was similar in both groups, whereas death-censored and overall graft survival were decreased in AKI kidney recipients. AKI kidney recipients showed higher frequencies of DGF and had a reduced eGFR at 7 days, three months and one and three years after RTx. However, mortality was noticeably lower compared to waiting list candidates. Rejection-free survival was similar between groups.ConclusionsIn our cohort, both short-term and long-term renal function was inferior in recipients of AKI kidneys, while patient survival was similar. Our data indicates that recipients of donor AKI kidneys should be carefully selected and additional factors impairing short- and long-term outcome should be minimized to prevent further deterioration of graft function.
| S-EPMC6415810 | biostudies-literature
Project description:Kidney transplantation from a hepatitis C virus (HCV)-positive donor to an HCV-negative recipient till recently has been a contraindication. In view of the excellent sustained virological response (SVR) rates with directly acting antiviral agents, HCV-positive donors are being considered for the HCV-negative recipients in a few centers. We report the successful transplantation of an HCV-negative recipient transplanted with an HCV-positive donor kidney. Donor was treated with sofosbuvir and ribavirin for 12 weeks. At 10th and 16th weeks of starting treatment, her HCV-RNA PCR was negative. Three weeks later, transplantation was performed with basiliximab induction and triple immunosuppression with tacrolimus, mycophenolate, and prednisolone. The recipient was administered sofosbuvir and ribavirin for 12 weeks. He attained good graft function with a stable creatinine. His serial alanine transaminases were normal on 3rd, 6th, and 12th months, respectively. Six months posttransplant his anti-HCV antibody, and HCV-RNA PCR were negative.
| S-EPMC6309394 | biostudies-other
Project description:BackgroundHistorically, liver allografts with >30% macrosteatosis (MaS) on donor biopsy have been associated with early allograft dysfunction and worse graft survival; however, successful outcomes have been reported in small cohorts. This study proposes an elevated MaS threshold for organ utilization without detriment to graft survival.MethodsThe UNOS Standard Transplant Analysis and Research database was evaluated for transplants between 2006-2015. Graft survival up to 1-year was evaluated by Kaplan-Meier (KM) survival analyses, and by univariate and multivariable logistic regression analyses, including donor and recipient characteristics. Odds ratios (OR) with 95% confidence intervals (CI) for risk of graft loss are reported.ResultsThirty-day risk of graft loss was increased with MaS as low as 10-19% (OR [95% CI] 1.301 [1.055-1.605], p<0.0001) and peaked with MaS 50-59% (2.921 [1.672-5.103]). At 1-year, risk of graft loss remained elevated with MaS 40-49% (1.465 [1.002-2.142]) and MaS 50-59% (1.978 [1.281-3.056], p = 0.0224). Multivariable models were created for Lower and Higher MELD recipients and MaS cutoffs were established. In Lower MELD recipients, organs with ≥50% MaS had increased risk of graft loss at 30 days (2.451 [1.541-3.897], p = 0.0008) and 1-year post-transplant (1.720 [1.224-2.418], p = 0.0125). Higher MELD recipients had increased risk of graft loss at 30 days with allografts showing MaS ≥40% (4.204 [1.440-5.076], p = 0.0016). At 1-year the risk remained increased, but MaS was not significant predictor of graft loss.048 [1.131-3.710], p = 0.0616). In both MELD cohorts, organs with MaS levels below threshold had similar survival to those transplanted without a donor biopsy.ConclusionsIn conjunction with recipient selection, organs with MaS up to 50% may be safely used without detriment to outcomes.
| S-EPMC7117730 | biostudies-literature
Project description:BackgroundThe use of hepatitis C virus-positive (HCV+) donors has expanded the donor pool for orthotopic heart transplantation (OHT). This study evaluated center-level trends and utilization of HCV+ donors for OHT.MethodsData were extracted from the Scientific Registry of Transplant Recipients on adults (≥18 y) undergoing OHT between January 1, 2016 and December 31, 2019. Centers performing <10 OHTs during the study period were excluded. Donor utilization rates were evaluated at the center level. Center-level characteristics were compared between centers performing HCV+ donor hepatitis C virus-negative (HCV-) recipient OHTs and those not utilizing HCV+ donors for HCV- recipients.ResultsA total of 10 134 patients underwent OHT, including 613 (6.05%) HCV+ donors transplanted into HCV- recipients. The number of HCV+ OHTs increased from 15 of 2512 (0.60%) in 2016 to 285 of 2490 (11.45%) in 2019 (P < 0.001). In 2016, among 105 centers performing OHTs, 7 (6.67%) utilized HCV+ donors compared to 2019 during which 55 (52.89%) of 104 centers utilized HCV+ donors (P < 0.001). In total, 57 of 107 (53.27%) centers utilized HCV+ donors during the study period. Centers utilizing HCV+ donors had higher overall donor utilization rates (7376/24 378 [30.26%] versus 3463/15 335 [22.58%], P < 0.001) and were higher volume as compared to nonutilizing centers (mean annual OHT volume 30.72 ± 1.21 versus 16.2 ± 1.40, P < 0.001).ConclusionsAlthough the use of HCV+ donors for OHT is rapidly expanding in the United States, almost half of transplant centers remain nonutilizers. Broader education and implementation of HCV+ donor protocols may be important in expanding OHT to more patients with end-stage heart failure.
| S-EPMC9015733 | biostudies-literature
Project description:UnlabelledThe rs738409 G>C single nucleotide polymorphism occurring in the patatin-like phospholipase 3 gene has been identified as a novel genetic marker for hepatic steatosis. Recent studies also associated rs738409 with fibrosis in hepatitis C (HCV). Therefore, we sought to determine the impact of donor and recipient rs738409 genotype on the progression of fibrosis after liver transplantation for HCV. This cohort study included 101 patients infected with HCV who underwent liver transplantation between January 2008, and June 2011. Donor and recipient rs738409 genotypes were determined from donor wedge biopsies and recipient explants. The time to Ishak stage 3 fibrosis, or HCV-related mortality/graft loss was analyzed by the Cox model adjusting for HCV-Donor Risk Index, warm ischemic time, pretransplant Model for Endstage Liver Disease (MELD) and viral load. The rs738409 CC variant was present in 56% of donors and 57% of recipients. The median follow-up period was 620 days. A total of 39 patients developed the primary outcome of ≥stage 3 fibrosis or HCV-related mortality/graft loss, the time to which differed by donor (P = 0.019) but not recipient (P = 0.89) genotype. In the multivariate model, donor GC or GG variants had 2.53 times the risk (95% confidence interval [CI] 1.25-5.02, P = 0.008) compared to CC variants. In the alternative endpoint: stage 3 fibrosis or all-cause mortality/graft loss, the effect of donor genotype was attenuated but remained significant at 1.98 (95% CI 1.11-3.53).ConclusionsThe rs738409 genotype is an important predictor of posttransplant outcome in HCV. Liver, and not adipocytes, is the site at which this effect occurs. Our finding may be useful in donor selection for liver transplantation with HCV, and may guide decisions regarding early antiviral treatment.
| S-EPMC7224311 | biostudies-literature
Project description:The introduction of living donor liver transplantation (LDLT) has been one of the most remarkable steps in the field of liver transplantation (LT). First introduced for children in 1989, its adoption for adults has followed only 10 years later. As the demand for LT continues to increase, LDLT provides life-saving therapy for many patients who would otherwise die awaiting a cadaveric organ. In recent years, LDLT has been shown to be a clinically safe addition to deceased donor liver transplantation (DDLT) and has been able to significantly extend the scarce donor pool. As long as the donor shortage continues to increase, LDLT will play an important role in the future of LT.
| S-EPMC2131378 | biostudies-other
Project description:Adult-to-adult living donors and recipients were studied to characterize patterns of liver growth and identify associated factors in a multicenter study. Three hundred and fifty donors and 353 recipients in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) receiving transplants between March 2003 and February 2010 were included. Potential predictors of 3-month liver volume included total and standard liver volumes (TLV and SLV), Model for End-Stage Liver Disease (MELD) score (in recipients), the remnant and graft size, remnant-to-donor and graft-to-recipient weight ratios (RDWR and GRWR), remnant/TLV, and graft/SLV. Among donors, 3-month absolute growth was 676 ± 251 g (mean ± SD), and percentage reconstitution was 80% ± 13%. Among recipients, GRWR was 1.3% ± 0.4% (8 < 0.8%). Graft weight was 60% ± 13% of SLV. Three-month absolute growth was 549 ± 267 g, and percentage reconstitution was 93% ± 18%. Predictors of greater 3-month liver volume included larger patient size (donors and recipients), larger graft volume (recipients), and larger TLV (donors). Donors with the smallest remnant/TLV ratios had larger than expected growth but also had higher postoperative bilirubin and international normalized ratio at 7 and 30 days. In a combined donor-recipient analysis, donors had smaller 3-month liver volumes than recipients adjusted for patient size, remnant or graft volume, and TLV or SLV (P = 0.004). Recipient graft failure in the first 90 days was predicted by poor graft function at day 7 (HR = 4.50, P = 0.001) but not by GRWR or graft fraction (P > 0.90 for each). Both donors and recipients had rapid yet incomplete restoration of tissue mass in the first 3 months, and this confirmed previous reports. Recipients achieved a greater percentage of expected total volume. Patient size and recipient graft volume significantly influenced 3-month volumes. Importantly, donor liver volume is a critical predictor of the rate of regeneration, and donor remnant fraction affects postresection function. Liver Transpl 21:79-88, 2015. © 2014 AASLD.
| S-EPMC4276514 | biostudies-literature