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1.
Am J Transplant ; 24(4): 619-630, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37940005

RESUMO

The recent shortage of the University of Wisconsin (UW) solution prompted increased utilization of histidine-tryptophan-ketoglutarate (HTK) solution for liver graft preservation. This contemporary study analyzed deceased donor liver transplant outcomes following preservation with HTK vs UW. Patients receiving deceased donor liver transplantations between January 1, 2019, and June 30, 2022, were retrospectively identified utilizing the Organ Procurement and Transplant Network database, stratified by preservation with HTK vs UW, and a propensity score matching analysis was performed. Outcomes assessed included rates of primary nonfunction, graft survival, and patient survival. There were 4447 patients in each cohort. Primary nonfunction occurred in 60 (1.35%) patients in the HTK group vs 25 (0.54%) in the UW group (P < .001). HTK was associated with lower 90-day graft survival (94.39% vs 96.09%; P < .001) and 90-day patient survival (95.97% vs 97.38%; P = .001). Unmatched donation after cardiac death-specific analysis of HTK vs UW demonstrated respective rates of primary nonfunction of 1.63% vs 0.82% (P = .20), 90-day graft survival of 92.50% vs 95.29% (P = .069), and 90-day patient survival of 93.90% vs 96.35% (P = .077). These results suggest that HTK may not be an equivalent preservation solution for deceased donor liver transplantation.


Assuntos
Transplante de Fígado , Soluções para Preservação de Órgãos , Humanos , Estudos Retrospectivos , Pontuação de Propensão , Doadores Vivos , Glucose , Manitol , Cloreto de Potássio , Procaína , Insulina , Glutationa , Alopurinol
2.
Transplant Direct ; 9(11): e1521, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37829245

RESUMO

Background: Organ donors supported by extracorporeal membrane oxygenation (ECMO) have historically been considered high-risk and are judiciously utilized. This study examines transplant outcomes using renal allografts from donors supported on ECMO for nondonation purposes. Methods: Retrospective review of the Gift of Life (Pennsylvania, New Jersey, Delaware) organ procurement organization database, cross-referenced to the Organ Procurement and Transplantation Network database, assessed kidney transplants using donors supported on venoarterial (VA) and venovenous (VV) ECMO for nondonation purposes. Transplants using VA- and VV-ECMO donors were compared with Kidney Donor Profile Index (KDPI)-stratified non-ECMO donors. Regression modeling of the entire ECMO and non-ECMO populations assessed ECMO as predictive of graft survival. Additional regression of the ECMO population alone assessed for donor features associated with graft survival. Results: Seventy-eight ECMO donors yielded 128 kidney transplants (VA: 80, VV: 48). Comparing outcomes using these donors to kidney transplants using organs from KDPI-stratified non-ECMO donors, VA- and VV-ECMO donor grafts conferred similar rates of delayed graft function and posttransplant renal function to KDPI-matched non-ECMO counterparts. VA-ECMO kidneys demonstrated superior graft survival compared with the lowest-quality (KDPI 86%-100%) non-ECMO kidneys and similar graft survival to KDPI <85% non-ECMO kidneys. VV-ECMO showed inferior graft survival to all but the lowest-quality (KDPI 86%-100%) non-ECMO kidneys. VV-ECMO, but not VA-ECMO, was associated with increased risk of graft loss on multivariable regression (hazard ratios-VA: 1.02, VV: 2.18). Higher KDPI, advanced age, increased body mass index, hypertension, and diabetes were identified as high-risk features of ECMO donors. Conclusions: Kidney transplantation using appropriately selected ECMO donors can safely expand the donor pool. Ongoing studies are necessary to determine best practice patterns using kidneys from these donors.

3.
Liver Transpl ; 29(11): 1151-1160, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37387680

RESUMO

Liver transplantation continues to face significant organ shortages and efficient utilization of marginal donors is paramount. This study evaluates the practice patterns and outcomes in liver transplantation when utilizing allografts from marginal donors who required extracorporeal membrane oxygenation (ECMO) support. We performed a retrospective review of the Gift of Life (PA, NJ, DE) organ-procuring organization database for transplants performed using donors supported on ECMO for nondonation purposes. These were cross-referenced to the transplant recipients within the Organ Procurement and Transplantation Network database, and the outcomes of liver transplants using donors on ECMO support were compared with those not requiring ECMO. Organ use and nonuse patterns were then evaluated in ECMO-supported donors, identifying the factors associated with nonuse compared with the factors associated with graft failure. Thirty-nine of the 84 ECMO-supported donors contributing at least one intra-abdominal organ for transplant donated a liver. Graft survival and patient survival up to 5 years were comparable between transplants from ECMO and non-ECMO-supported donors, and no cases of primary nonfunction were seen in the ECMO group. ECMO support was not associated with 1-year graft failure on regression modeling. Additional regression analyses within the ECMO donor population identified bacteremia (HR: 19.81) and elevated total bilirubin at donation (HR: 2.44) as predictive of post-transplant graft failure. Livers from donors supported on ECMO before donation appear safe to use in select transplant settings. Better understanding of the impact of predonation ECMO on liver allograft function will help guide the optimal use of these scarcely used donors.


Assuntos
Oxigenação por Membrana Extracorpórea , Transplante de Fígado , Obtenção de Tecidos e Órgãos , Humanos , Transplante de Fígado/efeitos adversos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Doadores de Tecidos , Transplante Homólogo , Sobrevivência de Enxerto , Estudos Retrospectivos
4.
Transpl Int ; 35: 10175, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35865863

RESUMO

Non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) has become the second leading cause of HCC-related liver transplantation in the United States. This study investigated post-transplant recurrence and survival for patients transplanted for NASH-related HCC compared to non-NASH HCC etiologies. Retrospective review of the United Network for Organ Sharing (UNOS) Organ Procurement and Transplantation Network (OPTN) database identified 7,461 patients with HCC-1,405 with underlying NASH and 6,086 with non-NASH underlying diseases. After propensity score matching (PSM) to account for patient- and tumor-related confounders 1,175 remained in each group. Primary outcomes assessed were recurrence rate and recurrence-free survival. Recurrent malignancy at 5 years post-transplant was lower in NASH compared to non-NASH patients (5.80 vs. 9.41%, p = 0.01). Recurrence-free survival, however, was similar at 5 years between groups. Patients with NASH-related HCC were less likely to have post-transplant recurrence than their non-NASH counterparts, although recurrence-free survival was similar at 5 years.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/cirurgia , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Estados Unidos
5.
Liver Transpl ; 28(4): 623-635, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34564931

RESUMO

The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) affects both recipient and donor populations in liver transplantation. Presently, it is unclear whether transplantation of macrosteatotic allografts is affected by the metabolic milieu of liver transplant recipients. This study investigates fatty liver disease at the intersection of donor and recipient. A retrospective review of the Organ Procurement and Transplantation database identified 5167 NASH and 26,289 non-NASH transplant recipients who received transplants from January 1, 2004, to June 12, 2020. A total of 12,569 donors had allografts with no macrosteatosis (<5%), 16,140 had mild macrosteatosis (5%-29%), and 2747 had moderate to severe macrosteatosis (≥30%). Comparing recipients with NASH to propensity score-matched (PSM) recipients without NASH demonstrated noninferior graft and patient survival up to 10 years in patients with NASH. Similar trends were observed in subgroup analyses of transplants within each strata of allograft macrosteatosis. Assessing allograft macrosteatosis specifically in the NASH population demonstrated that allografts with ≥30% macrosteatosis were associated with reduced early graft survival (30 days, 93.32% versus 96.54% [P = 0.02]; 1 year, 84.53% versus 88.99% [P = 0.05]) compared with PSM grafts with <30% macrosteatosis. Long-term graft survival at 5 and 10 years, however, was similar. The use of carefully selected macrosteatotic allografts can be successful in both recipients with NASH and recipients without NASH. The metabolic environment of patients with NASH does not appear to adversely affect outcomes with regard to the allograft when controlled for numerous confounders. It is, however, important to remain cognizant of the potential for high-risk macrosteatotic allografts to negatively affect outcomes.


Assuntos
Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Aloenxertos , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/cirurgia , Estudos Retrospectivos , Doadores de Tecidos , Resultado do Tratamento
6.
Transpl Int ; 34(6): 1052-1064, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33884677

RESUMO

Rates of simultaneous liver kidney (SLK) transplantation in the United States have progressively risen. On 8/10/17, the Organ Procurement and Transplantation Network implemented a policy defining criteria for SLK, with a "Safety Net" to prioritize kidney allocation to liver recipients with ongoing renal failure. We performed a retrospective review of the United Network for Organ Sharing (UNOS) database to evaluate policy impact on SLK, kidney after liver (KAL) and kidney transplant alone (KTA). Rates and outcomes of SLK and KAL transplants were compared, as was utilization of high-quality kidney allografts with Kidney Donor Profile Indices (KDPI) <35%. Here, SLK transplants comprised 9.0% and 4.5% of total postpolicy liver and kidney transplants compared to 10.2% and 5.5% prior. Policy enactment did not affect 1-year graft or patient survival for SLK and KAL populations. Less postpolicy SLK transplants utilized high-quality kidney allografts; in all transplant settings, outcomes using high-quality grafts remained stable. These findings suggest that policy implementation has reduced kidney allograft use in SLK transplantation, although both SLK and KAL rates have recently increased. Despite decreased high-quality kidney allograft use, SLK and KAL outcomes have remained stable. Additional studies and long-term follow-up will ensure optimal organ access and sharing.


Assuntos
Obtenção de Tecidos e Órgãos , Sobrevivência de Enxerto , Humanos , Rim , Fígado , Políticas , Estudos Retrospectivos , Fatores de Risco , Estados Unidos
7.
Artif Organs ; 45(7): 682-695, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33349946

RESUMO

The ever-widening gap between organ supply and demand has resulted in an organ shortage crisis that affects patients all over the world. For decades, static cold storage (SCS) was the gold standard preservation strategy because of its simplicity and cost-effectiveness, but the rising unmet demand for donor organ transplants has prompted investigation into preservation strategies that can expand the available donor pool. Through ex vivo functional assessment of the organ prior to transplant, newer methods to preserve organs such as perfusion-based therapy can potentially expand the available organ pool. This review will explain the physiologic rationale for SCS before exploring the advantages and disadvantages associated with the two broad classes of preservation strategies that have emerged to address the crisis: hypothermic and normothermic machine perfusion. A detailed analysis of how each preservation strategy works will be provided before investigating the current status of clinical data for each preservation strategy for the kidney, liver, pancreas, heart, and lung. For some organs there is robust data to support the use of machine perfusion technologies over SCS, and in others the data are less clear. Nonetheless, machine perfusion technologies represent an exciting frontier in organ preservation research and will remain a crucial component of closing the gap between organ supply and recipient demand.


Assuntos
Preservação de Órgãos/métodos , Perfusão/métodos , Transplantes , Humanos , Refrigeração , Traumatismo por Reperfusão/prevenção & controle
8.
Case Rep Transplant ; 2021: 5159934, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34987880

RESUMO

INTRODUCTION: Hepatitis A infection (HAV) is generally characterized by an acute icteric illness or may have a subclinical self-limited course, although rarely, can result in fulminant hepatitis and death. In 2019, the City of Philadelphia declared a public health emergency due to an HAV outbreak. We are reporting a series of four cases of acute liver failure (ALF) requiring liver transplantation (LT) due to acute HAV. METHODS: Chart review and case descriptions of four patients with acute HAV-related ALF who were expeditiously evaluated, listed as Status 1A, and who underwent LT between August 2019 and October 2019 at Thomas Jefferson University Hospital. RESULTS: All four patients presented with acute hepatocellular jaundice and had a positive HAV IgM, and all other causes of ALF were excluded. All four cases met the American Association for the Study of Liver Diseases (AASLD) criteria for ALF. Three of the four cases met King's College Criteria of poor prognosis for nonacetaminophen-induced ALF. All four patients underwent successful LT and were discharged six to twelve days postoperatively. One patient died of disseminated Aspergillus infection five months after LT, while the others have had excellent clinical outcomes shown by one-year follow-ups. All four explants had remarkably similar histological changes, revealing acute hepatitis with massive necrosis accompanied by a prominent lymphoplasmacytic inflammatory infiltrate and bile ductular proliferation. CONCLUSION: Although rare, patients presenting with acute HAV need close monitoring as they may rapidly progress to ALF. Early referral to a transplant center afforded timely access to LT and yielded overall good one-year survival. Widespread HAV vaccination for high-risk individuals is an essential strategy for preventing disease and curbing such future outbreaks.

9.
Mol Cancer Res ; 18(4): 612-622, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31941754

RESUMO

Deregulated RNA-binding proteins (RBP), such as Argonaute 2 (AGO2), mediate tumor-promoting transcriptomic changes during carcinogenesis, including hepatocellular carcinoma (HCC). While AGO2 is well characterized as a member of the RNA-induced silencing complex (RISC), which represses gene expression through miRNAs, its role as a bona fide RBP remains unclear. In this study, we investigated AGO2's role as an RBP that regulates the MYC transcript to promote HCC. Using mRNA and miRNA arrays from patients with HCC, we demonstrate that HCCs with elevated AGO2 levels are more likely to have the mRNA transcriptome deregulated and are associated with poor survival. Moreover, AGO2 overexpression stabilizes the MYC transcript independent of miRNAs. These observations provide a novel mechanism of gene regulation by AGO2 and provide further insights into the potential functions of AGO2 as an RBP in addition to RISC. IMPLICATIONS: Authors demonstrate that the RBP Argonaute 2 stabilizes the MYC transcript to promote HCC.


Assuntos
Proteínas Argonautas/genética , Carcinoma Hepatocelular/genética , Genes myc , Neoplasias Hepáticas/genética , Proteínas Proto-Oncogênicas c-myc/genética , Animais , Proteínas Argonautas/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Xenoenxertos , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos Nus , Camundongos SCID , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transfecção
10.
J Natl Cancer Inst ; 112(8): 847-854, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31728517

RESUMO

BACKGROUND: Immunosuppressive regimens associated with organ transplantation increase the risk of developing cancer. Transplant candidates and recipients with prostate cancer are often treated, even if low-risk features would ordinarily justify active surveillance. METHODS: Using SEER-Medicare, we identified 163 676 men aged 66 years and older diagnosed with nonmetastatic prostate cancer. History of solid organ transplant was identified using diagnosis or procedure codes. A propensity score-matched cohort was identified by matching transplanted men to nontransplanted controls by age, race, region, year, T-stage, grade, comorbidity, and cancer therapy. Fine-Gray competing risk models assessed associations between transplant status and prostate cancer-specific mortality (PCSM) and overall mortality (OM). RESULTS: We identified 620 men (0.4%) with transplant up to 10 years before (n = 320) or 5 years after (n = 300) prostate cancer diagnosis and matched them to 3100 men. At 10 years, OM was 55.7% and PCSM was 6.0% in the transplant cohort compared with 42.4% (P < .001) and 7.6% (P = .70) in the nontransplant cohort, respectively. Adjusted models showed no difference in PCSM for transplanted men (hazard ratio = 0.88, 95% confidence interval = 0.61 to 1.27, P = .70) or differences by prostate cancer therapy. Among 334 transplanted men with T1-2N0, well or moderately differentiated "low-risk" prostate cancer, PCSM was similar for treated and untreated men (hazard ratio = 0.92, 95% confidence interval = 0.47 to 1.81). CONCLUSIONS: Among men aged 66 years and older with prostate cancer, an organ transplant is associated with higher OM but no observable difference in PCSM. These findings suggest men with prostate cancer and previous or future organ transplantation should be managed per usual standards of care, including consideration of active surveillance for low-risk cancer characteristics.


Assuntos
Imunossupressores/efeitos adversos , Transplante de Órgãos/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Neoplasias da Próstata/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Humanos , Masculino , Medicare/estatística & dados numéricos , Estadiamento de Neoplasias , Transplante de Órgãos/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Pontuação de Propensão , Neoplasias da Próstata/complicações , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Fatores de Risco , Programa de SEER , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/estatística & dados numéricos , Resultado do Tratamento , Estados Unidos/epidemiologia
11.
Transplant Rev (Orlando) ; 33(4): 231-236, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31272764

RESUMO

BACKGROUND: In patients who require orthotopic liver transplant (OLT), cardiac surgery may be needed to optimize preoperative cardiac status for OLT. The aim of this systematic review was to evaluate patient characteristics and outcomes of those undergoing staged versus concomitant cardiac procedures with OLT. METHODS: An electronic search was performed to identify all case reports and series, from which patient-level data was extracted regarding cardiac procedures associated with OLT. After assessment for inclusion and exclusion criteria, 26 articles were pooled for systematic review. RESULTS: Overall, 49 patients were included in the analysis, of whom 12 (24%) underwent staged procedures and 37 (76%) underwent concomitant procedures. The median age was lower in the staged group [staged: 51 (IQR, 43.8-59.2) years vs. concomitant: 60 (IQR, 55.0-64.0) years, p = .02]. Other baseline characteristics were comparable between the two groups. For staged procedures, the median time between heart procedures and OLT was 2 (IQR, 1.0-3.5) months. The most commonly reported cardiac procedures were coronary artery bypass graft (CABG) [staged: 4/12 (33.3%) vs. concomitant: 21/37 (56.8%), p = .28], aortic valve replacement (AVR) [staged: 3/12 (25.0%) vs. concomitant: 19/37 (51.2%), p = .21], and transcatheter aortic valve replacement (TAVR) [staged: 4/12 (33.3%) vs. concomitant: 0/37 (0%), p = .002]. Regarding outcomes, there was a significantly shorter post-OLT hospital stay for those who had staged procedures versus those who had concomitant procedures [staged: 8 (IQR, 5-13) days vs. concomitant: 17 (IQR, 14-24) days, p = .007]. However, both groups had similar in-hospital mortality rates [staged: 1/12 (8.3%) vs. concomitant: 4/37 (10.8%), p = 1.0]. Overall survival stratified between the two groups was comparable. CONCLUSIONS: Patients who underwent the staged approach had a shorter post-transplant hospital stay, but comparable survival with respect to those who underwent concomitant cardiac procedures and OLT.


Assuntos
Ponte de Artéria Coronária/métodos , Hepatectomia/métodos , Mortalidade Hospitalar/tendências , Transplante de Fígado/métodos , Substituição da Valva Aórtica Transcateter/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Prognóstico , Medição de Risco , Análise de Sobrevida
12.
Sci Rep ; 9(1): 3369, 2019 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-30833661

RESUMO

The MYC oncogene is dysregulated in approximately 30% of liver cancer. In an effort to exploit MYC as a therapeutic target, including in hepatocellular carcinoma (HCC), strategies have been developed on the basis of MYC amplification or gene translocation. Due to the failure of these strategies to provide accurate diagnostics and prognostic value, we have developed a Negative Elongation Factor E (NELFE)-Dependent MYC Target (NDMT) gene signature. This signature, which consists of genes regulated by MYC and NELFE, an RNA binding protein that enhances MYC-induced hepatocarcinogenesis, is predictive of NELFE/MYC-driven tumors that would otherwise not be identified by gene amplification or translocation alone. We demonstrate the utility of the NDMT gene signature to predict a unique subtype of HCC, which is associated with a poor prognosis in three independent cohorts encompassing diverse etiologies, demographics, and viral status. The application of gene signatures, such as the NDMT signature, offers patients access to personalized risk assessments, which may be utilized to direct future care.


Assuntos
Carcinoma Hepatocelular/genética , Genes myc/genética , Neoplasias Hepáticas/genética , Fatores de Transcrição/genética , Fatores Etários , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco
13.
Liver Transpl ; 25(4): 598-609, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30716208

RESUMO

Highly effective direct-acting antiviral (DAA) therapy has transformed outcomes of liver transplantation in hepatitis C virus (HCV) patients. We examined longer-term outcomes in HCV-positive recipients in the DAA era and analyzed the Scientific Registry of Transplant Recipients for primary adult, single-organ, nonfulminant liver transplant recipients in the United States from January 1, 2008 to June 30, 2018. Graft loss was compared among HCV-positive liver transplant recipients who received either an HCV-negative or HCV-positive donor (donor [D]-/recipient [R]+; D+/R+) and HCV-negative liver transplant recipients who received a HCV-negative donor (D-/R-). The groups were further divided between the pre-DAA and DAA eras. There were 52,526 patients included: 31,193 were D-/R- patients; 18,746 were D-/R+ patients; and 2587 were D+/R+ patients. The number of D-/R+ transplants decreased from 2010 in 2008 to 1334 in 2017, with this decline particularly noticeable since 2015. D-/R+ patients in the DAA era (n = 7107) were older, had higher rates of hepatocellular carcinoma, and lower Model for End-Stage Liver Disease scores than those in the pre-DAA era. Graft survival improved for all recipients in the DAA era but improved most dramatically in HCV-positive recipients: D-/R+ 1-year survival was 92.4% versus 88.7% and 3-year survival was 83.7% versus 77.7% (DAA versus pre-DAA era, respectively) compared with D-/R- 1-year survival of 92.7% versus 91.0% and 3-year survival of 85.7% versus 84.0% (DAA versus pre-DAA era, respectively). The magnitude of improvement in 3-year graft survival was almost 4-fold greater for D-/R+ patients. The 3-year survival for D+/R+ patients was similar to HCV-negative patients. In conclusion, the number of liver transplants for HCV has decreased by more than one-third over the past decade. Graft survival among HCV-positive recipients has increased disproportionately in the DAA era with HCV-positive recipients now achieving similar outcomes to non-HCV recipients.


Assuntos
Antivirais/administração & dosagem , Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/epidemiologia , Hepatite C Crônica/tratamento farmacológico , Transplante de Fígado/efeitos adversos , Adulto , Idoso , Aloenxertos/efeitos dos fármacos , Aloenxertos/virologia , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/virologia , Feminino , Rejeição de Enxerto/virologia , Sobrevivência de Enxerto/efeitos dos fármacos , Hepacivirus/isolamento & purificação , Hepatite C Crônica/transmissão , Hepatite C Crônica/virologia , Humanos , Estimativa de Kaplan-Meier , Fígado/efeitos dos fármacos , Fígado/virologia , Transplante de Fígado/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros/estatística & dados numéricos , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
14.
Hepatology ; 69(6): 2381-2395, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30706517

RESUMO

Direct-acting antiviral (DAA) therapy has altered the frequency and outcome of liver transplantation (LT) for hepatitis C virus (HCV). The high efficacy and tolerability of DAA therapy has also created a rationale for utilizing HCV-viremic (HCV-RNA-positive) donors, including into HCV-negative recipients. We examined trends in frequency of organ utilization and graft survival in recipients of HCV-viremic donors (HCV-RNA positive as measured by nucleic acid testing [NAT]). Data were collected from the Scientific Registry of Transplant Recipients (SRTR) on adult patients who underwent a primary, single-organ, deceased donor LT from January 1, 2008 to January 31, 2018. Outcomes of HCV-negative transplant recipients (R- ) who received an allograft from donors who were HCV-RNA positive (DNAT+ ) were compared to outcomes for R- patients who received organs from donors who were HCV-RNA negative (DNAT- ). There were 11,270 DNAT- /R- ; 4,748 DNAT- /R+ ; 87 DNAT+ /R- ; and 753 DNAT+ /R+ patients, with 2-year graft survival similar across all groups: DNAT- /R- 88%; DNAT- /R+ 88%; DNAT+ /R- 86%; and DNAT+ /R+ 90%. Additionally, there were 2,635 LTs using HCV antibody-positive donors (DAb+ ): 2,378 DAb+ /R+ and 257 DAb+ /R- . The annual number of DAb+ /R- transplants increased from seven in 2008 to 107 in 2017. In the post-DAA era, graft survival improved for all recipients, with 3-year survival of DAb+ /R- patients and DAb+ /R+ patients increasing to 88% from 79% and to 85% from 78%, respectively. Conclusion: The post-DAA era has seen increased utilization of HCV-viremic donor livers, including HCV-viremic livers into HCV-negative recipients. Early graft outcomes are similar to those of HCV-negative recipients. These results support utilization of HCV-viremic organs in selected recipients both with and without HCV infection.


Assuntos
Hepatite C Crônica/tratamento farmacológico , Transplante de Fígado/métodos , Fígado/virologia , Sistema de Registros , Transplantados/estatística & dados numéricos , Viremia/cirurgia , Adulto , Antivirais/uso terapêutico , Estudos de Coortes , Feminino , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Hepacivirus/isolamento & purificação , Hepatectomia/métodos , Hepatite C Crônica/patologia , Humanos , Incidência , Estimativa de Kaplan-Meier , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Obtenção de Tecidos e Órgãos/métodos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos
15.
Liver Transpl ; 24(10): 1470-1475, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30080954

RESUMO

Liver transplantation was made a reality through the bravery, innovation, and persistence of Dr. Thomas Starzl. His death in 2017, at the age of 90, makes us pause to consider how far the field has come since its inception by this remarkable pioneer. It also is an opportunity to evaluate the continued novel innovations which contribute to the growth and potential for liver transplantation in the future. The liver transplant community in 2017 continued to be most significantly challenged by an overwhelming disparity between the need for liver transplant and the shortage of donor organs. The many ways in which this critical shortage are being addressed are examined in this article. The continued debate about equitable and efficacious organ allocation, "the liver wars," has dominated much of the recent past, while efforts to optimize current organ availability have also been aggressively pursued. Efforts to optimize the use of marginal and expanded criteria organs have escalated in recent years and have been accompanied by rigorous scientific evaluation. The ongoing opioid epidemic, combined with the approval and availability of highly effective hepatitis C treatment options, has allowed the increased use of HCV positive organs in HCV positive and negative recipients. Machine perfusion, both cold and warm, has moved solidly into the liver transplant world potentiating optimization of marginal donors and also offering potential modulation of liver grafts (ie, gene therapy, stem cell therapy, and defatting). Finally, pharmacological and mechanical interventions in DCD procurement techniques have contributed to improved outcomes in DCD transplants. All of these are explored in this article as a tribute to innovative spirit of Dr. Starzl and his continued impact on liver transplant today.


Assuntos
Doença Hepática Terminal/cirurgia , Transplante de Fígado/tendências , Obtenção de Tecidos e Órgãos/normas , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/mortalidade , História do Século XX , História do Século XXI , Humanos , Transplante de Fígado/história , Transplante de Fígado/métodos , Transplante de Fígado/normas , Preservação de Órgãos/métodos , Preservação de Órgãos/tendências , Índice de Gravidade de Doença , Obtenção de Tecidos e Órgãos/tendências , Resultado do Tratamento , Estados Unidos/epidemiologia , Listas de Espera/mortalidade
17.
Hepatobiliary Surg Nutr ; 7(1): 29-31, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29531941

RESUMO

Congenital membranous occlusion of the inferior vena cava (IVC) in pediatric liver recipients may present with outflow occlusion and if unrecognized, result in graft loss. Prompt evaluation of outflow obstruction in the setting of unexplained inflow compromise is paramount. We report a case of successful IVC reconstruction in a patient with recurrent hepatic artery thrombosis (HAT). A 2-year-old child with history of two liver transplantations developed fevers, ascites, and abdominal tenderness one month after her second liver transplant. Hepatic duplex revealed decreased flow in the hepatic artery and IVC venogram revealed patent hepatic veins with occlusion of the suprahepatic IVC. We performed reconstruction of her suprahepatic IVC to intrapericardial IVC using an end-to-side technique after complete mobilization of the liver. Recovery was uneventful and the patient has been doing well for the last 5 years.

18.
Surgery ; 163(3): 582-586, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29370929

RESUMO

BACKGROUND: Studies comparing orthotopic liver transplantation to margin negative resection for patients with small unifocal hepatocellular carcinoma have not controlled for degree of cirrhosis. METHODS: The National Cancer Database was used to identify patients with preserved liver function (Model for End-stage Liver Disease score ≤12) who underwent orthotopic liver transplantation or margin negative resection for American Joint Committee on Cancer stage I hepatocellular carcinoma lesions <3 cm between 2010 and 2013. Multivariable and Cox regression adjusting for age, demographics, comorbid disease burden, Model for End-stage Liver Disease score, tumor size, and operation were used to compare overall survival between cohorts. RESULTS: In the study, 241 (53%) patients underwent orthotopic liver transplantation. In addition, 219 (47%) underwent margin negative resection. On multivariable regression, patients having a Charlson comorbidity score ≥2 were more likely to undergo orthotopic liver transplantation, (odds ratio 1.94, P=.03). African American patients (odds ratio 0.44, P=.02), and patients of advanced age (odds ratio 0.92, P<.001) were more likely to undergo margin negative resection. Patients undergoing orthotopic liver transplantation had longer overall survival than those undergoing margin negative resection (median OS not reached versus 67.6 months, P<.001). Multivariable Cox regression identified surgical procedure as the only independent determinant of survival with margin negative resection conferring a nearly 3-fold increased risk of death (hazard ratio 2.86, P<.001). CONCLUSION: Orthotopic liver transplantation offers a survival advantage relative to margin negative resection for patients with small unifocal hepatocellular carcinoma and preserved liver function.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Idoso , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
20.
Ann Surg ; 265(5): 1016-1024, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27232249

RESUMO

OBJECTIVE: We sought to evaluate outcomes and predictors of renal allograft futility (RAF-patient death or need for renal replacement therapy at 3 months) after simultaneous liver-kidney transplantation (SLKT). BACKGROUND: Model for End-Stage Liver Disease (MELD) prioritization of liver recipients with renal dysfunction has significantly increased utilization of SLKT. Data on renal outcomes after SLKT in the highest MELD recipients are scarce, as are accurate predictors of recovery of native kidney function. Without well-established listing guidelines, SLKT potentially wastes renal allografts in both high-acuity liver recipients at risk for early mortality and recipients who may regain native kidney function. METHODS: A retrospective single-center multivariate regression analysis was performed for adult patients undergoing SLKT (January 2004 to August 2014) to identify predictors of RAF. RESULTS: Of 331 patients dual-listed for SLKT, 171 (52%) expired awaiting transplant, 145 (44%) underwent SLKT, and 15 (5%) underwent liver transplantation alone. After SLKT, 39% experienced delayed graft function and 20.7% had RAF. Compared with patients without RAF, RAF recipients had greater MELD scores, length of hospitalization, intraoperative base deficit, incidence of female donors, kidney and liver donor risk indices, kidney cold ischemia, and inferior overall survival. Multivariate predictors of RAF included pretransplant dialysis duration, kidney cold ischemia, kidney donor risk index, and recipient hyperlipidemia. CONCLUSIONS: With 20% short-term loss of transplanted kidneys after SLKT, our data strongly suggest that renal transplantation should be deferred in liver recipients at high risk for RAF. Consideration for a kidney allocation variance to allow for delayed renal transplantation after liver transplantation may prevent loss of scarce renal allografts.


Assuntos
Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Doadores de Tecidos , Centros Médicos Acadêmicos , Adulto , Estudos de Coortes , Terapia Combinada , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Transplante de Rim/mortalidade , Falência Hepática/cirurgia , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Cuidados Pós-Operatórios/métodos , Prognóstico , Análise de Regressão , Insuficiência Renal/cirurgia , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos
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