Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 33
Filtrar
1.
J Investig Med High Impact Case Rep ; 11: 23247096231207480, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37843100

RESUMO

Homeopathic remedies made primarily from eggshells, and therefore calcium, can be marketed for treatment of back pain and vaginal discharge. We present a case of a 23-year-old otherwise healthy woman who presented with acute liver failure (ALF) ultimately requiring liver transplantation as a result of taking increased doses of a homeopathic product with the primary ingredient of eggshells. Although relatively uncommon compared with medications such as acetaminophen, herbal supplements have been reported to cause drug-induced liver injury (DILI), thought to be primarily due to contaminants. This is the first known report of DILI resulting from a homeopathic product with the primary ingredient of eggshells, and it demonstrates the importance of early ALF recognition and treatment, as well as the importance of practicing caution when using homeopathic supplements.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Falência Hepática Aguda , Transplante de Fígado , Materia Medica , Feminino , Humanos , Adulto Jovem , Adulto , Materia Medica/efeitos adversos , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/terapia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Suplementos Nutricionais
2.
Am J Transplant ; 23(2): 291-293, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36804136

RESUMO

AL amyloidosis is a rare condition characterized by the overproduction of an unstable free light chain, protein misfolding and aggregation, and extracellular deposition that can progress to multiorgan involvement and failure. To our knowledge, this is the first worldwide report to describe triple organ transplantation for AL amyloidosis and triple organ transplantation using thoracoabdominal normothermic regional perfusion recovery with a donation from a circulatory death (DCD) donor. The recipient was a 40-year-old man with multiorgan AL amyloidosis with a terminal prognosis without multiorgan transplantation. An appropriate DCD donor was selected for sequential heart, liver, and kidney transplants via our center's thoracoabdominal normothermic regional perfusion pathway. The liver was additionally placed on an ex vivo normothermic machine perfusion, and the kidney was maintained on hypothermic machine perfusion while awaiting implantation. The heart transplant was completed first (cold ischemic time [CIT]: 131 minutes), followed by the liver transplant (CIT: 87 minutes, normothermic machine perfusion: 301 minutes). Kidney transplantation was performed the following day (CIT: 1833 minutes). He is 8 months posttransplant without evidence of heart, liver, or kidney graft dysfunction or rejection. This case highlights the feasibility of normothermic recovery and storage modalities for DCD donors, which can expand transplant opportunities for allografts previously not considered for multiorgan transplantations.


Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina , Transplante de Rim , Obtenção de Tecidos e Órgãos , Masculino , Humanos , Adulto , Preservação de Órgãos , Doadores de Tecidos , Perfusão , Fígado , Morte
3.
Liver Transpl ; 29(3): 318-330, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35980605

RESUMO

Liver transplantation (LT) is a life-saving treatment for patients with acute liver failure (ALF). Currently, there are few detailed data regarding long-term outcomes after LT for ALF. We combined prospective data from the Acute Liver Failure Study Group (ALFSG) Registry with those of the Scientific Registry of Transplant Recipients (SRTR) to assess outcomes among consecutive patients with ALF listed for LT. Cohort analysis of detailed pretransplantation data for patients listed for LT for ALF in the ALFSG Registry between January 1998 and October 2018 matched with transplantation-related data from the SRTR. Primary outcomes were 1- and 3-year post-LT patient survival. Secondary outcome was receipt of LT; independent associations with successful receipt of LT were determined using multivariable logistic regression. Of 624 patients with ALF listed for LT, 398 (64%) underwent LT, 100 (16%) died without LT, and 126 (20%) recovered spontaneously. Among LT recipients, etiologies included seronegative/indeterminate (22%), drug-induced liver injury (18%), acetaminophen overdose (APAP; 16%), and viral hepatitis (15%). The 1- and 3-year post-LT patient survival rates were 91% and 90%, respectively. Comparing those dying on the waiting list versus with those who received LT, the former had more severe multiorgan failure, reflected by increased vasopressor use (65% vs. 22%), mechanical ventilation (84% vs. 57%), and renal replacement therapy (57% vs. 30%; p < 0.0001 for all). After adjusting for relevant covariates, age (adjusted odds ratio [aOR] 1.02, 95% confidence interval [CI] 1.00-1.04), APAP etiology (aOR 2.72, 95% CI 1.42-5.23), requirement for vasopressors (aOR 4.19, 95% CI 2.44-7.20), Grade III/IV hepatic encephalopathy (aOR 2.47, 95% CI 1.29-4.72), and Model for End-Stage Liver Disease (MELD) scores (aOR 1.05, 95% CI 1.02-1.09; p < 0.05 for all) were independently associated with death without receipt of LT. Post-LT outcomes for ALF are excellent in this cohort of very ill patients. The development of multiorgan failure while on the transplantation list and APAP ALF etiology were associated with a lower likelihood of successful receipt of LT.


Assuntos
Doença Hepática Terminal , Falência Hepática Aguda , Transplante de Fígado , Humanos , Acetaminofen/efeitos adversos , Transplante de Fígado/efeitos adversos , Estudos Prospectivos , Doença Hepática Terminal/complicações , Índice de Gravidade de Doença , Estudos de Coortes , Falência Hepática Aguda/etiologia
4.
Clin Transplant ; 36(6): e14610, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35143698

RESUMO

This study used the prospective National Surgical Quality Improvement Program (NSQIP) Transplant pilot database to analyze surgical complications after liver transplantation (LT) in LT recipients from 2017to 2019. The primary outcome was surgical complication requiring intervention (Clavien-Dindo grade II or greater) within 90 days of transplant. Of the 1684 deceased donor and 109 living donor LT cases included from 29 centers, 38% of deceased donor liver recipients and 47% of living donor liver recipients experienced a complication. The most common complications included biliary complications (19% DDLT; 31% LDLT), hemorrhage requiring reoperation (14% DDLT; 9% LDLT), and vascular complications (6% DDLT; 9% LDLT). Management of biliary leaks (35.3% ERCP, 38.0% percutaneous drainage, 26.3% reoperation) and vascular complications (36.2% angioplasty/stenting, 31.2% medication, 29.8% reoperation) was variable. Biliary (aHR 5.14, 95% CI 2.69-9.8, P < .001), hemorrhage (aHR 2.54, 95% CI 1.13-5.7, P = .024) and vascular (aHR 2.88, 95% CI .85-9.7, P = .089) complication status at 30-days post-transplant were associated with lower 1-year patient survival. We conclude that biliary, hemorrhagic and vascular complications continue to be significant sources of morbidity and mortality for LT recipients. Understanding the different risk factors for complications between deceased and living donor liver recipients and standardizing complication management represent avenues for continued improvement.


Assuntos
Transplante de Fígado , Doadores Vivos , Humanos , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Melhoria de Qualidade , Estudos Retrospectivos , Resultado do Tratamento
5.
Am J Transplant ; 22(6): 1699-1704, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35080128

RESUMO

Limited case series describe conflicting results regarding the safety of checkpoint inhibitors (CPI) prior to liver transplantation (LT). We reviewed single-center data on all consecutive patients who underwent LT for hepatocellular carcinoma treated with CPI between January 1, 2018, and January 30, 2021. Time from CPI to LT, immunosuppression, biopsy-proven acute cellular rejection (BPACR), graft loss and death were evaluated. Five patients with a mean age 65 (range 61-71) years underwent LT after CPI with nivolumab. Time from last CPI to LT ranged from 0.3 to 11 months. Two patients with <3 months from the last dose of CPI to LT developed BPACR and severe hepatic necrosis, one of whom required retransplantation with recurrent BPACR but without recurrent graft loss over 38 months of follow up. None of the patients who underwent LT >3 months from the last dose of CPI had BPACR. In conclusion, pretransplant use of CPIs, particularly within 90 days of LT, was associated with BPACR and immune-mediated hepatic necrosis. Future multicenter studies should consider a sufficient interval from the last dose of CPI to LT to mitigate the risk for adverse immune-mediated outcomes and graft loss.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Idoso , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Pessoa de Meia-Idade , Necrose/induzido quimicamente , Nivolumabe/efeitos adversos , Estudos Retrospectivos
6.
JAMA Surg ; 157(3): 189-198, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34985503

RESUMO

IMPORTANCE: Ischemic cold storage (ICS) of livers for transplant is associated with serious posttransplant complications and underuse of liver allografts. OBJECTIVE: To determine whether portable normothermic machine perfusion preservation of livers obtained from deceased donors using the Organ Care System (OCS) Liver ameliorates early allograft dysfunction (EAD) and ischemic biliary complications (IBCs). DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial (International Randomized Trial to Evaluate the Effectiveness of the Portable Organ Care System Liver for Preserving and Assessing Donor Livers for Transplantation) was conducted between November 2016 and October 2019 at 20 US liver transplant programs. The trial compared outcomes for 300 recipients of livers preserved using either OCS (n = 153) or ICS (n = 147). Participants were actively listed for liver transplant on the United Network of Organ Sharing national waiting list. INTERVENTIONS: Transplants were performed for recipients randomly assigned to receive donor livers preserved by either conventional ICS or the OCS Liver initiated at the donor hospital. MAIN OUTCOMES AND MEASURES: The primary effectiveness end point was incidence of EAD. Secondary end points included OCS Liver ex vivo assessment capability of donor allografts, extent of reperfusion syndrome, incidence of IBC at 6 and 12 months, and overall recipient survival after transplant. The primary safety end point was the number of liver graft-related severe adverse events within 30 days after transplant. RESULTS: Of 293 patients in the per-protocol population, the primary analysis population for effectiveness, 151 were in the OCS Liver group (mean [SD] age, 57.1 [10.3] years; 102 [67%] men), and 142 were in the ICS group (mean SD age, 58.6 [10.0] years; 100 [68%] men). The primary effectiveness end point was met by a significant decrease in EAD (27 of 150 [18%] vs 44 of 141 [31%]; P = .01). The OCS Liver preserved livers had significant reduction in histopathologic evidence of ischemia-reperfusion injury after reperfusion (eg, less moderate to severe lobular inflammation: 9 of 150 [6%] for OCS Liver vs 18 of 141 [13%] for ICS; P = .004). The OCS Liver resulted in significantly higher use of livers from donors after cardiac death (28 of 55 [51%] for the OCS Liver vs 13 of 51 [26%] for ICS; P = .007). The OCS Liver was also associated with significant reduction in incidence of IBC 6 months (1.3% vs 8.5%; P = .02) and 12 months (2.6% vs 9.9%; P = .02) after transplant. CONCLUSIONS AND RELEVANCE: This multicenter randomized clinical trial provides the first indication, to our knowledge, that normothermic machine perfusion preservation of deceased donor livers reduces both posttransplant EAD and IBC. Use of the OCS Liver also resulted in increased use of livers from donors after cardiac death. Together these findings indicate that OCS Liver preservation is associated with superior posttransplant outcomes and increased donor liver use. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02522871.


Assuntos
Transplante de Fígado , Morte , Feminino , Humanos , Fígado , Transplante de Fígado/métodos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Preservação de Órgãos/métodos , Perfusão/métodos
7.
Liver Transpl ; : 318-330, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37160076

RESUMO

ABSTRACT: Liver transplantation (LT) is a life-saving treatment for patients with acute liver failure (ALF). Currently, there are few detailed data regarding long-term outcomes after LT for ALF. We combined prospective data from the Acute Liver Failure Study Group (ALFSG) Registry with those of the Scientific Registry of Transplant Recipients (SRTR) to assess outcomes among consecutive patients with ALF listed for LT. Cohort analysis of detailed pretransplantation data for patients listed for LT for ALF in the ALFSG Registry between January 1998 and October 2018 matched with transplantation-related data from the SRTR. Primary outcomes were 1- and 3-year post-LT patient survival. Secondary outcome was receipt of LT; independent associations with successful receipt of LT were determined using multivariable logistic regression. Of 624 patients with ALF listed for LT, 398 (64%) underwent LT, 100 (16%) died without LT, and 126 (20%) recovered spontaneously. Among LT recipients, etiologies included seronegative/indeterminate (22%), drug-induced liver injury (18%), acetaminophen overdose (APAP; 16%), and viral hepatitis (15%). The 1- and 3-year post-LT patient survival rates were 91% and 90%, respectively. Comparing those dying on the waiting list versus with those who received LT, the former had more severe multiorgan failure, reflected by increased vasopressor use (65% vs. 22%), mechanical ventilation (84% vs. 57%), and renal replacement therapy (57% vs. 30%; p < 0.0001 for all). After adjusting for relevant covariates, age (adjusted odds ratio [aOR] 1.02, 95% confidence interval [CI] 1.00-1.04), APAP etiology (aOR 2.72, 95% CI 1.42-5.23), requirement for vasopressors (aOR 4.19, 95% CI 2.44-7.20), Grade III/IV hepatic encephalopathy (aOR 2.47, 95% CI 1.29-4.72), and Model for End-Stage Liver Disease (MELD) scores (aOR 1.05, 95% CI 1.02-1.09; p < 0.05 for all) were independently associated with death without receipt of LT. Post-LT outcomes for ALF are excellent in this cohort of very ill patients. The development of multiorgan failure while on the transplantation list and APAP ALF etiology were associated with a lower likelihood of successful receipt of LT.

8.
Clin J Gastroenterol ; 14(6): 1718-1724, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34643885

RESUMO

Immune checkpoint inhibitors (ICI) have been used to treat hepatocellular carcinoma (HCC) since 2017. The safety of ICIs in the setting of solid organ transplantation remains controversial. When used in the post-transplant setting, ICIs have been associated with high allograft rejection rates, but there are few published reports on the use of ICIs prior to transplant. We present the first reported case of rescue liver re-transplantation after loss of the first allograft due to severe acute rejection with extensive hepatic necrosis in the setting of pre-transplant ICI therapy with the PD-1 inhibitor nivolumab. It is likely that the durable immune response triggered by nivolumab contributes to graft rejection, therefore extreme caution should be taken when using ICIs before transplant until further investigation has been conducted on their safety in the pre-transplant setting.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Rejeição de Enxerto/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Nivolumabe/efeitos adversos
9.
Clin Transplant ; 35(7): e14338, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33948985

RESUMO

Growing research supports an increased survival benefit of combined heart and kidney transplantation in patients with both heart and renal failure. As a result, the frequency of these combined transplants continues to increase. Despite this trend, little has been done to quantify the impact of chronic illness in this population. We identified adult recipients of combined heart-kidney transplant from the Scientific Registry of Transplant Recipients (SRTR) database between 2005 and 2018. We focused on renal disease secondary to diabetes and duration of dialysis as markers of chronic illness. The primary outcome was post-transplant mortality. Our final multivariable Cox proportional hazard model found that diabetes-associated renal disease (HR 1.57, 95% CI 1.14-2.15, p = .01) and dialysis duration (HR 1.08, 95% CI 1.01-1.15, p = .02) were significant predictors of post-transplant mortality. Given the significant impact of dialysis duration and renal disease secondary to diabetes mellitus, these chronically ill patients should be closely examined for conditions such as peripheral vascular disease and frailty, which have been shown to affect mortality in heart transplant recipients and are prevalent in the chronic dialysis population.


Assuntos
Diabetes Mellitus , Falência Renal Crônica , Transplante de Rim , Adulto , Sobrevivência de Enxerto , Humanos , Rim , Falência Renal Crônica/cirurgia , Sistema de Registros , Diálise Renal , Transplantados
10.
Transplant Direct ; 7(5): e692, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33912659

RESUMO

Despite an increasing demand for liver transplantation in older patients, our understanding of posttransplant outcomes in older recipients is limited to basic recipient and graft survival. Using National Surgical Quality Improvement Program Transplant, we tracked early outcomes after liver transplantation for patients >65. METHODS: We conducted a retrospective analysis of patients in National Surgical Quality Improvement Program Transplant between March 1, 2017 and March 31, 2019. Recipients were followed for 1 y after transplant with follow-up at 30, 90, and 365 d. Data were prospectively gathered using standard definitions across all sites. RESULTS: One thousand seven hundred thirty-one adult liver transplants were enrolled; 387 (22.4%) were >65 y old. The majority of older recipients were transplanted for hepatocellular carcinoma. The older cohort had a lower lab Model for End-Stage Liver Disease and was less likely to be hospitalized at time of transplant. Overall, older recipients had higher rates of pneumonia but no difference in intensive care unit length of stay (LOS), total LOS, surgical site infection, or 30-d readmission. Subgroup analysis of patients with poor functional status revealed a significant difference in intensive care unit and total LOS. Pneumonia was even more common in older patients and had a significant impact on overall survival. CONCLUSIONS: By targeting patients with hepatocellular carcinoma and lower Model for End-Stage Liver Diseases, transplant centers can achieve nearly equivalent outcomes in older recipients. However, older recipients with poor functional status require greater resources and are more likely to develop pneumonia. Pneumonia was strongly associated with posttransplant survival and represents an opportunity for improvement. By truly understanding the outcomes of elderly and frail recipients, transplant centers can improve outcomes for these higher-risk recipients.

11.
Liver Transpl ; 27(1): 27-33, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32578297

RESUMO

Spontaneous survival rates in acute liver failure (ALF) are vastly improved by liver transplantation (LT). However, the value of induction agents beyond steroids continues to be debated. To understand the potential benefit of different induction regimens in the ALF population, we compared overall survival of recipients undergoing LT in the United States for ALF. Using the Scientific Registry of Transplant Recipients, we assessed the impact of induction immunosuppression (IS) in a cohort of 3754 first-time LT recipients with a diagnosis of ALF from 2002 to 2018. Induction IS therapy was grouped into steroid-only induction, use of antithymocyte globulin (ATG), or interleukin 2 receptor antibody. Other regimens were excluded from analysis. Survival analysis was estimated via Cox proportional hazards models and expressed as hazard ratios (HRs). In LT for ALF, the use of induction agents beyond steroids is increasingly frequent over the last 2 decades. The use of ATG is associated with worse overall survival, even after adjusting for donor and recipient factors, with HR of 1.24 (95% confidence interval, 1.00-1.53; P = 0.05). An elevated serum creatinine, recipient and donor age, and Black ethnicity, were all associated with reduced survival, whereas maintenance IS with calcineurin inhibitors (CNIs) was associated with improved survival. Although adjunct induction therapy has become more common, our analysis shows that compared with a steroid-only induction regimen, the addition of ATG is associated with worse overall survival after LT for ALF. CNI maintenance was highly protective, suggesting that an IS strategy focusing on corticosteroid-only induction followed by CNI maintenance may offer the best overall survival rate.


Assuntos
Transplante de Rim , Falência Hepática Aguda , Transplante de Fígado , Alemtuzumab , Anticorpos Monoclonais Humanizados , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Imunossupressores/efeitos adversos , Falência Hepática Aguda/cirurgia , Transplante de Fígado/efeitos adversos , Ácido Micofenólico , Resultado do Tratamento , Estados Unidos/epidemiologia
12.
Liver Transpl ; 27(2): 190-199, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32419266

RESUMO

Declining a liver offer during organ procurement likely increases the risk of discard, but the specifics around late reallocation remain obscure. This voluntarily submitted, prospectively collected data describe late declines and the ultimate disposition of 893 livers. Once a liver suffered an intraoperative decline, only 49% of recovered livers were transplanted. Livers declined ≥80 minutes prior to cross-clamp were transplanted 80% of the time versus livers declined ≥80 minutes after cross-clamp, which were transplanted 45% of the time. The final disposition of these livers was into a predetermined backup patient (51%) or required an out-of-sequence expedited allocation (42%). Prerecovery imaging and prerecovery biopsy did not influence the ability to reallocate a liver, and livers from donors after circulatory death are rarely successfully reallocated. In conclusion, this study begins to shed light on this seemingly common practice. A total of 85% of centers had an intraoperative decline, but 4% of centers accounted for 25% of the declines. Organ procurement organizations often enter expedited liver allocation, and instituting a cross-clamp delay to allow for reallocation may influence the disposition of these liver grafts. Expedited allocation was more time consuming than allocation into a predetermined backup. Although a certain number of intraoperative declines probably suggests a healthy amount of donor selection aggressiveness at the time of the initial organ offer, the 47% risk of discard of livers declined intraoperatively suggests that United Network for Organ Sharing should consider systematically collecting data about intraoperative declines so we can learn more about this event that influences organ utilization.


Assuntos
Transplante de Fígado , Obtenção de Tecidos e Órgãos , Seleção do Doador , Humanos , Fígado/cirurgia , Transplante de Fígado/efeitos adversos , Doadores de Tecidos
13.
Am J Transplant ; 19(9): 2622-2630, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30980484

RESUMO

The National Surgical Quality Program (NSQIP) Transplant was designed by transplant surgeons from the ground up to track posttransplant outcomes beyond basic recipient and graft survival. After an initial pilot phase, the program has expanded to 29 participating sites and enrolled more than 4300 recipient-donor pairs into the database, including 2876 complete kidney transplant cases. In this analysis, surgical site infection (SSI), urinary tract infection (UTI), and reoperation/intervention were evaluated for kidney transplant recipients. We observed impressive variation in the crude incidence between sites for SSI (0%-17%), UTI (0%-14%), and reoperation/intervention (0%-25%). After adjustment for donor and recipient factors, 2 sites were outliers with respect to their incidence of UTI. For the first time, the field of transplantation has data that demonstrate variation in kidney recipient surgical outcomes between sites. More importantly, NSQIP Transplant provides a powerful platform to improve care beyond basic patient and graft survival.


Assuntos
Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Transplante de Rim/mortalidade , Transplante de Rim/métodos , Adulto , Idoso , Coleta de Dados , Bases de Dados Factuais , Feminino , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Sistema de Registros , Reoperação/estatística & dados numéricos , Doadores de Tecidos , Resultado do Tratamento , Estados Unidos , Infecções Urinárias/epidemiologia , Infecções Urinárias/etiologia
14.
Cell ; 177(3): 608-621.e12, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30955891

RESUMO

Normal tissues accumulate genetic changes with age, but it is unknown if somatic mutations promote clonal expansion of non-malignant cells in the setting of chronic degenerative diseases. Exome sequencing of diseased liver samples from 82 patients revealed a complex mutational landscape in cirrhosis. Additional ultra-deep sequencing identified recurrent mutations in PKD1, PPARGC1B, KMT2D, and ARID1A. The number and size of mutant clones increased as a function of fibrosis stage and tissue damage. To interrogate the functional impact of mutated genes, a pooled in vivo CRISPR screening approach was established. In agreement with sequencing results, examination of 147 genes again revealed that loss of Pkd1, Kmt2d, and Arid1a promoted clonal expansion. Conditional heterozygous deletion of these genes in mice was also hepatoprotective in injury assays. Pre-malignant somatic alterations are often viewed through the lens of cancer, but we show that mutations can promote regeneration, likely independent of carcinogenesis.


Assuntos
Hepatopatias/patologia , Fígado/metabolismo , Regeneração , Animais , Doença Crônica , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Hidrolases/deficiência , Hidrolases/genética , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Cirrose Hepática/patologia , Hepatopatias/genética , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Regeneração/fisiologia , Canais de Cátion TRPP/genética , Canais de Cátion TRPP/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Sequenciamento do Exoma
15.
Am J Transplant ; 19(7): 2108-2115, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30887634

RESUMO

The National Surgical Quality Program (NSQIP) Transplant program was designed by transplant surgeons from the ground up to track posttransplant outcomes beyond basic recipient and graft survival. After an initial pilot phase, the program has expanded to 29 participating sites and enrolled more than 4300 recipient-donor pairs into the database, including 1444 completed liver transplant cases. In this analysis, surgical site infection (SSI), urinary tract infection (UTI), and unplanned reoperation/intervention after liver transplantation were evaluated. We observed impressive variation in the crude incidence between sites for SSI (0%-29%), UTI (0%-10%), and reoperation/intervention (0%-57%). After adjustment for donor and recipient factors, at least 1 site was identified as an outlier for each of the analyzed outcomes. For the first time, the field of transplantation has data that demonstrate variation in liver recipient outcomes beyond death and graft survival between sites. More importantly, NSQIP Transplant provides a powerful platform to improve care beyond basic patient and graft survival.


Assuntos
Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto , Hepatopatias/mortalidade , Transplante de Fígado/mortalidade , Complicações Pós-Operatórias/mortalidade , Infecção da Ferida Cirúrgica/mortalidade , Infecções Urinárias/mortalidade , Adulto , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Humanos , Hepatopatias/cirurgia , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Prognóstico , Reoperação/mortalidade , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/patologia , Infecções Urinárias/etiologia , Infecções Urinárias/patologia
16.
World J Hepatol ; 11(2): 242-249, 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30820274

RESUMO

BACKGROUND: Only one case of liver transplantation for hepatic adenoma has previously been reported for patients with rupture and uncontrolled hemorrhage. We present the case of a massive ruptured hepatic adenoma with persistent hemorrhagic shock and toxic liver syndrome which resulted in a two-stage liver transplantation. This is the first case of a two-stage liver transplantation performed for a ruptured hepatic adenoma. CASE SUMMARY: A 23 years old African American female with a history of pre-diabetes and oral contraceptive presented to an outside facility complaining of right-sided chest pain and emesis for one day. She was found to be in hemorrhagic shock due to a massive ruptured hepatic hepatic adenoma. She underwent repeated embolizations with interventional radiology with ongoing hemorrhage and the development of renal failure, hepatic failure, and hemodynamic instability, known as toxic liver syndrome. In the setting of uncontrolled hemorrhage and toxic liver syndrome, a hepatectomy with porto-caval anastomosis was performed with liver transplantation 15 h later. She tolerated the anhepatic stage well, and has done well over one year later. CONCLUSION: When toxic liver syndrome is recognized, liver transplantation with or without hepatectomy should be considered before the patient becomes unstable.

17.
Pediatr Transplant ; 23(1): e13323, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30447034

RESUMO

INTRODUCTION: There is a mismatch that exists in donor liver organ supply and demand. DCD livers represents a potential source to increase the number of liver grafts available for use in pediatric recipients; however, there has been hesitancy to use such organs. We evaluated patient and allograft outcomes in pediatric liver transplant recipients of DCD livers. METHODS: The UNOS database was queried to examine outcomes in all liver transplant recipients from 1993 to 2017. Patients were then divided according to adult and pediatric status, DBD or DCD allograft status, and era of transplant. Donor and recipient demographic data were examined, and patient and allograft survival were calculated. A P-value of <0.05 was considered to be significant. RESULTS: A total of 57 pediatric recipients received a DCD liver allograft. DCD recipients were older than DBD recipients. There was no difference in the final PELD score between the groups. There were no differences in causes of allograft failure between the DCD and DBD groups. Importantly, the overall allograft survival in the DCD and DBD groups was similar, as was allograft survival based on era. CONCLUSION: Pediatric liver transplant recipients of DCD allografts have comparable patient and allograft survival when compared to DBD allograft recipients. Use of DCD allografts in the pediatric liver transplant population should be strongly considered to increase the donor organ pool.


Assuntos
Morte , Seleção do Doador/métodos , Sobrevivência de Enxerto , Transplante de Fígado , Adolescente , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Humanos , Lactente , Recém-Nascido , Transplante de Fígado/mortalidade , Masculino , Avaliação de Resultados em Cuidados de Saúde , Pediatria , Estudos Retrospectivos , Análise de Sobrevida , Doadores de Tecidos , Transplante Homólogo
18.
Liver Transpl ; 23(2): 135-142, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27656864

RESUMO

Budd-Chiari syndrome (BCS) is a rare disease resulting from obstruction of the hepatic venous outflow tract that typically presents with abdominal pain, jaundice, and ascites without frank liver failure. However, BCS may also evolve more rapidly to acute liver failure (ALF). In this study, we describe the clinical features, treatment, and outcomes of ALF due to BCS and compare our results with those in the published literature. Twenty of the 2344 patients enrolled in the Acute Liver Failure Study Group (ALFSG) registry since 1998 presented with a clinical diagnosis of BCS. An additional 19 patients of ALF-BCS in the English language literature were reviewed and compared with the ALFSG cases. Most ALF-BCS patients were white (84%) and female (84%) in their fourth decade. A hypercoagulable state was noted in 63% of patients. BCS was diagnosed by Doppler ultrasonography or abdominal computed tomography in all patients. Liver biopsies (n = 6) all had evidence of severe pericentral necrosis. Treatments used included most commonly anticoagulation (71%), but also transjugular intrahepatic portosystemic shunt (TIPS; 37%) and orthotopic liver transplantation (37%). In-hospital mortality was approximately 60%. In conclusion, BCS is a rare cause of ALF and mandates prompt diagnosis and management for successful outcomes. Once the diagnosis is confirmed, prompt anticoagulation is recommended in conjunction with evaluation for malignancy or thrombophilic disorder. Mortality may have improved in recent years with use of TIPS and/or orthotopic liver transplantation compared with prior published reports. Liver Transplantation 23 135-142 2017 AASLD.


Assuntos
Síndrome de Budd-Chiari/complicações , Falência Hepática Aguda/etiologia , Transplante de Fígado , Derivação Portossistêmica Transjugular Intra-Hepática , Doenças Raras/complicações , Adulto , Anticoagulantes/uso terapêutico , Biópsia , Síndrome de Budd-Chiari/mortalidade , Síndrome de Budd-Chiari/patologia , Síndrome de Budd-Chiari/terapia , Feminino , Mortalidade Hospitalar , Humanos , Falência Hepática Aguda/mortalidade , Falência Hepática Aguda/patologia , Falência Hepática Aguda/terapia , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Ultrassonografia Doppler , Adulto Jovem
19.
Kidney Int Rep ; 1(4): 221-229, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27942610

RESUMO

BACKGROUND: The survival benefit from simultaneous liver-kidney transplantation (SLK) over liver transplant alone (LTA) in recipients with moderate renal dysfunction is not well understood. Moreover, the impact of deceased donor organ quality in SLK transplant survival has not been well described in the literature. METHODS: The Scientific Registry of Transplant Recipients was studied for adult recipients receiving LTA (N=2,700) or SLK (N=1,361) transplantation with moderate renal insufficiency between 2003 and 2013. The study cohort was stratified into four groups based on serum creatinine (Scr< 2 mg/dL versus Scr≥ 2 mg/dL) and dialysis status at listing and at transplant. The patients with end-stage renal disease and requiring acute dialysis more than three months before transplantation were excluded. A propensity score (PS)-matching was performed in each stratified groups to factor out imbalances between the SLK and LTA regarding covariates distribution and to reduce measured confounding. Donor quality was assessed with liver-donor risk index (L-DRI). The primary outcome of interest was post-transplant mortality. RESULTS: On multivariable PS-matched Cox proportional hazard models, SLK led to decrease in post-transplant mortality compared to LTA across all four groups, but only reached statistical significance (HR 0.77; 95% CI, 0.62-0.96) in the recipients not exposed to dialysis and Scr≥ 2 mg/dL at transplant (mortality incidence rate per patient-year 5.7% in SLK vs. 7.6% in LTA, p=0.005). The decrease in mortality was observed among SLK recipients with better quality donors (L-DRI<1.5). CONCLUSIONS: Exposure to pre-transplantation dialysis and donor quality affected overall survival among SLK recipients.

20.
Clin Transplant ; 30(10): 1242-1249, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27423055

RESUMO

Recipient diabetes accounts for ~34% of end-stage renal disease in patients awaiting renal transplantation and has been linked to poor graft function. We conducted a single-center, open-label, randomized controlled trial to determine whether moderately intense glucose control during allograft reperfusion would reduce the incidence of poor graft function. Adult diabetics undergoing deceased donor renal transplant were randomized to moderately intense glucose control (n=30) or standard control (n=30). The primary outcome was poor graft function (dialysis within seven days of transplant or failure of serum creatinine to fall by 10% for three consecutive days). Recipients with moderately intense glucose control had less poor graft function in the intention-to-treat (43.3% vs 73.3%, P=.02) and per-protocol analysis (43.2% vs 81%, P<.01). Recipients with moderately intense control also had higher glomerular filtration rate (GFR) at 30 days after transplant in the per-protocol and intention-to-treat analyses. There were no episodes of severe hypoglycemia in either group and no differences in mortality, seizures, stroke, graft loss, or biopsy-proven rejection. Moderately intense glucose control at the time of allograft reperfusion reduces the incidence of poor graft function in diabetic renal transplant recipients and improves glomerular filtration rate at 30 days.


Assuntos
Função Retardada do Enxerto/prevenção & controle , Nefropatias Diabéticas/cirurgia , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Falência Renal Crônica/cirurgia , Transplante de Rim , Assistência Perioperatória/métodos , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Função Retardada do Enxerto/epidemiologia , Função Retardada do Enxerto/etiologia , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Hiperglicemia/sangue , Hiperglicemia/complicações , Hiperglicemia/diagnóstico , Hipoglicemia/sangue , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Incidência , Análise de Intenção de Tratamento , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...