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1.
Am J Transplant ; 22 Suppl 2: 204-309, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35266621

RESUMO

This year was marked by the COVID-19 pandemic, which altered transplant program activity and affected waitlist and transplant outcomes. Still, 8906 liver transplants were performed, an all-time high, across 142 centers in the United States, and pretransplant as well as graft and patient survival metrics, continued to improve. Living donation activity decreased after several years of growth. As of June 30, 2020, 98989 liver transplant recipients were alive with a functioning graft, and in the context of increasing liver transplant volume, the size of both the adult and pediatric liver transplant waitlists have decreased. On February 4, 2020, shortly before the pandemic began, a new liver distribution policy based on acuity circles was implemented, replacing donor service area- and region-based boundaries. A policy change to direct pediatric livers to pediatric recipients led to an increase in deceased donor transplant rates and a decrease in pretransplant mortality rate among children, although the absolute number of pediatric transplants did not increase in 2020. Among adults, alcohol-associated liver disease became the predominant indication for liver transplant in 2020. After implementation of the National Liver Review Board and lower waitlist priority for most exception cases in 2019, fewer liver transplants were being performed via exception points, and the transplant rate between those with and without hepatocellular carcinoma has equalized. Women continue to experience higher pretransplant mortality and lower rates of liver transplant than men.


Assuntos
COVID-19 , Obtenção de Tecidos e Órgãos , Adulto , COVID-19/epidemiologia , Criança , Feminino , Sobrevivência de Enxerto , Humanos , Fígado , Masculino , Pandemias , SARS-CoV-2 , Doadores de Tecidos , Estados Unidos/epidemiologia , Listas de Espera
2.
Am J Transplant ; 21 Suppl 2: 208-315, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33595192

RESUMO

This year was notable for changes to exception points determined by the geographic median allocation Model for End-Stage Liver Disease (MELD) and implementation of the National Liver Review Board, which took place on May 14, 2019. The national acuity circle liver distribution policy was also implemented but reverted to donor service area- and region-based boundaries after 1 week. In 2019, growth continued in the number of new waiting list registrations (12,767) and transplants performed (8,896), including living-donor transplants (524). Compared with 2018, living-donor liver transplants increased 31%. Women continued to have a lower deceased-donor transplant rate and a higher pretransplant mortality rate than men. The median waiting time for candidates with a MELD of 15-34 decreased, while the number of transplants performed for patients with exception points decreased. These changes may have been related to the policy changes that took effect in May 2019, which increased waiting list priority for candidates without exception status. Hepatitis C continued to decline as an indication for liver transplant, as the proportion of liver transplant recipients with alcohol-related liver disease and clinical profiles consistent with non-alcoholic steatohepatitis increased. Graft and patient survival have improved despite changing recipient demographics including older age, higher MELD, and higher prevalence of obesity and diabetes.


Assuntos
Doença Hepática Terminal , Transplante de Fígado , Obtenção de Tecidos e Órgãos , Idoso , Doença Hepática Terminal/cirurgia , Feminino , Sobrevivência de Enxerto , Humanos , Doadores Vivos , Masculino , Índice de Gravidade de Doença , Doadores de Tecidos , Listas de Espera
3.
Am J Transplant ; 20 Suppl s1: 542-568, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31898411

RESUMO

Direct acting antivirals (DAAs) have fundamentally changed the treatment of hepatitis C virus (HCV) infection and reduced the discard rate of HCV-infected organs by offering a treatment option with a high likelihood of cure posttransplant. This has spurred increased interest in transplanting organs from HCV-positive donors into recipients both with and without HCV. In this chapter, we examine data from 2007 to 2018 to determine trends in HCV (+) donor transplants across various organ types. Since 2015, willingness to accept HCV (+) organs increased for candidates waitlisted for kidney, lung, heart, and pancreas transplant, but decreased for those listed for intestine transplant. For candidates listed for liver transplant, willingness to accept HCV (+) organs decreased from 2007 to 2017, but began increasing in 2017. Willingness to accept was not concentrated in a single US geographic area, and there was substantial variation among transplant programs and donation service areas. Numbers of anti-HCV (+) donor kidney, heart, lung, and liver transplants have increased considerably in the past few years. Short-term allograft survival for kidney and liver transplant recipients of anti-HCV (+) organs appears to be comparable to that for recipients of anti-HCV (-) organs in an unadjusted analysis. However, an unadjusted analysis indicates that long-term allograft survival may be worse. Kidney transplant between HCV-infected donors and uninfected recipients with posttransplant DAA treatment is an emerging area. Short-term data are promising, with similar 1-year allograft survival compared with HCV-uninfected donor to HCV-uninfected recipient kidney transplants in unadjusted analyses. However, long-term data are lacking and close monitoring in the future is warranted.


Assuntos
Transmissão de Doença Infecciosa/prevenção & controle , Seleção do Doador/organização & administração , Hepacivirus , Hepatite C Crônica/epidemiologia , Transplante de Fígado/estatística & dados numéricos , Doadores de Tecidos/provisão & distribuição , Listas de Espera , Hepatite C Crônica/transmissão , Hepatite C Crônica/virologia , Humanos
4.
Am J Transplant ; 20 Suppl s1: 193-299, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31898413

RESUMO

Data on adult liver transplants performed in the US in 2018 are notable for (1) continued growth in numbers of new waitlist registrants (11,844) and transplants performed (8250); (2) continued increase in the transplant rate (54.5 per 100 waitlist-years); (3) a precipitous decline in waitlist registrations and transplants for hepatitis-C-related indications; (4) increases in waitlist registrants and recipients with alcoholic liver disease and with clinical profiles consistent with non-alcoholic fatty liver disease; (5) increased use of hepatitis C virus antibody-positive donor livers; and (6) continued improvement in graft survival despite changing recipient characteristics such as older age and higher rates of obesity and diabetes. Variability in transplant rates remained by candidate race, hepatocellular carcinoma status, urgency status, and geography. The volume of pediatric liver transplants was relatively unchanged. The highest rate of pre-transplant mortality persisted for children aged younger than 1 year. Children underwent transplant at higher acuity than in the past, as evidenced by higher model for end-stage liver disease/pediatric end-stage liver disease scores and listings at status 1A and 1B at transplant. Despite higher illness severity scores at transplant, pediatric graft and patient survival posttransplant have improved over time.


Assuntos
Transplante de Fígado/estatística & dados numéricos , Sistema de Registros , Alocação de Recursos , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/métodos , Listas de Espera , Sobrevivência de Enxerto , Humanos , Estados Unidos
5.
Am J Transplant ; 19 Suppl 2: 184-283, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30811890

RESUMO

Data on adult liver transplants performed in the US in 2017 are notable for (1) continued growth in numbers of new waitlist registrants (11,514) and of transplants performed (8,082); (2) continued increase in the transplant rate (51.5 per 100 waitlist-years); (3) a precipitous decrease in waitlist registrations and transplants for hepatitis C-related indications; (4) reciprocal increases in waitlist registrants and recipients with alcoholic liver disease and with clinical profiles consistent with non-alcoholic fatty liver disease; and (5) continued improvement in graft survival despite changing recipient characteristics such as older age and higher rates of obesity. Variability in transplant rates remained by candidate race, presence of hepatocellular carcinoma, urgency status (status 1A versus model for end-stage liver disease (MELD) score >35), and geography. More than half of all children listed for liver transplant in 2017 were aged younger than 5 years in 2017, and the highest rate of pretransplant mortality persisted for children aged younger than 1 year. Children underwent transplant at higher acuity than the past, as evidenced by higher MELD/pediatric end-stage liver disease scores and listings at status 1A and 1B. Higher acuity at transplant is likely due to lack of access to suitable donor organs, which has been compensated for by persistent trends toward use of partial or split liver grafts and ABO-incompatible grafts. Despite higher illness severity scores at transplant, pediatric graft and patient survival posttransplant have improved over time.


Assuntos
Sobrevivência de Enxerto , Transplante de Fígado/métodos , Sistema de Registros/estatística & dados numéricos , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/métodos , Relatórios Anuais como Assunto , Humanos , Estados Unidos , Listas de Espera
6.
Am J Transplant ; 18 Suppl 1: 172-253, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29292603

RESUMO

Data on adult liver transplants performed in the US in 2016 are no-table for (1) the largest total number of transplants performed (7841); (2) the shortest median waiting time in recent history (11.3 months); (3) continued reduction in waitlist registrations and transplants for hepatitis C-related indications; (4) increasing numbers of patients whose clinical profiles are consistent with non-alcoholic fatty liver disease; and (5) equilibration of transplant rates in patients with and without hepatocellular carcinoma. Despite the increase in the number of available organs, waitlist mortality remained an important concern. Graft survival rates continued to improve. In 2016, 723 new active candidates were added to the pediatric liver transplant waiting list, down from a peak of 826 in 2005. The number of prevalent candidates (on the list on December 31 of the given year) was stable, 408 active and 169 inactive. The number of pediatric living donor liver transplants decreased from a peak of 79 in 2015 to 62 in 2016, with most from donors closely related to the recipients. Graft survival continued to improve over the past decade among recipients of deceased donor and living donor livers.


Assuntos
Relatórios Anuais como Assunto , Sobrevivência de Enxerto , Transplante de Fígado , Obtenção de Tecidos e Órgãos , Listas de Espera , Humanos , Sistema de Registros , Doadores de Tecidos , Estados Unidos
7.
Am J Transplant ; 17 Suppl 1: 174-251, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28052604

RESUMO

Several notable developments in adult liver transplantation in the US occurred in 2015. The year saw the largest number of liver transplants to date, leading to reductions in median waiting time, in waitlist mortality for all model for end-stage liver disease categories, and in the number of candidates on the waiting list at the end of the year. Numbers of additions to the waiting list and of liver transplants performed in patients with hepatitis C virus infection decreased for the first time in recent years. However, other diagnoses, such as non-alcoholic fatty liver disease and alcoholic cirrhosis, became more prevalent. Despite large numbers of severely ill patients undergoing liver transplant, graft survival rates continued to improve. The number of new active candidates added to the pediatric liver transplant waiting list in 2015 was 689, down from a peak of 826 in 2005. The number of prevalent pediatric candidates (on the list on December 31 of the given year) continued to decline, to 373 active and 195 inactive candidates. The number of pediatric liver transplants peaked at 613 in 2008 and was 580 in 2015. The number of living donor pediatric liver transplants increased to its highest level, 79, in 2015; most were from donors closely related to the recipients. Pediatric graft survival rates continued to improve.


Assuntos
Relatórios Anuais como Assunto , Sobrevivência de Enxerto , Transplante de Fígado , Alocação de Recursos , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/métodos , Humanos , Imunossupressores , Resultado do Tratamento , Estados Unidos , Listas de Espera
8.
Am J Transplant ; 16 Suppl 2: 69-98, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26755264

RESUMO

The median waiting time for patients with MELD ≥ 35 decreased from 18 days in 2012 to 9 days in 2014, after implementation of the Share 35 policy in June 2013. Similarly, mortality among candidates listed with MELD ≥ 35 decreased from 366 per 100 waitlist years in 2012 to 315 in 2014. The number of new active candidates added to the pediatric liver transplant waiting list in 2014 was 655, down from a peak of 826 in 2005. The number of prevalent candidates (on the list on December 31 of the given year) continued to decline, 401 active and 173 inactive. The number of deceased donor pediatric liver transplants peaked at 542 in 2008 and was 478 in 2014. The number of living donor liver pediatric transplants was 52 in 2014; most were from donors closely related to the recipients. Graft survival continued to improve among pediatric recipients of deceased donor and living donor livers.


Assuntos
Doença Hepática Terminal/cirurgia , Transplante de Fígado/métodos , Transplante de Fígado/estatística & dados numéricos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Doença Hepática Terminal/epidemiologia , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Doadores Vivos , Pessoa de Meia-Idade , Fatores de Tempo , Doadores de Tecidos , Resultado do Tratamento , Estados Unidos , Listas de Espera , Adulto Jovem
9.
Am J Transplant ; 15 Suppl 2: 1-28, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25626341

RESUMO

During 2013, 10,479 adult candidates were added to the liver transplant waiting list, compared with 10,185 in 2012; 5921 liver transplants were performed, and 211 of the transplanted organs were from living donors. As of December 31, 2013, 15,027 candidates were registered on the waiting list, including 12,407 in active status. The most significant change in allocation policy affecting liver waitlist trends in 2013 was the Share 35 policy, whereby organs from an entire region are available to candidates with model for end-stage liver disease scores of 35 or higher. Median waiting time for such candidates decreased dramatically, from 14.0 months in 2012 to 1.4 months in 2013, but the effect on waitlist mortality is unknown. The number of new active pediatric candidates added to the liver transplant waiting list increased to 693 in 2013. Transplant rates were highest for candidates aged younger than 1 year (275.6 per 100 waitlist years) and lowest for candidates aged 11 to 17 years (97.0 per 100 waitlist years). Five-year graft survival was 71.7% for recipients aged younger than 1 year, 74.9% for ages 1 to 5 years, 78.9% ages 6 to 10 years, and 77.4% for ages 11 to 17 years.


Assuntos
Relatórios Anuais como Assunto , Hepatopatias/cirurgia , Transplante de Fígado/estatística & dados numéricos , Alocação de Recursos , Doadores de Tecidos , Listas de Espera , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Humanos , Lactente , Recém-Nascido , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos , Adulto Jovem
10.
Am J Transplant ; 14(8): 1817-27, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25041339

RESUMO

This exploratory phase II study evaluated the safety and efficacy of belatacept in de novo adult liver transplant recipients. Patients were randomized (N = 260) to one of the following immunosuppressive regimens: (i) basiliximab + belatacept high dose [HD] + mycophenolate mofetil (MMF), (ii) belatacept HD + MMF, (iii) belatacept low dose [LD] + MMF, (iv) tacrolimus + MMF, or (v) tacrolimus alone. All received corticosteroids. Demographic characteristics were similar among groups. The proportion of patients who met the primary end point (composite of acute rejection, graft loss, death by month 6) was higher in the belatacept groups (42­48%) versus tacrolimus groups (15­38%), with the highest number of deaths and grafts losses in the belatacept LD group. By month 12, the proportion surviving with a functioning graft was higher with tacrolimus + MMF (93%) and lower with belatacept LD (67%) versus other groups (90%: basiliximab + belatacept HD; 83%: belatacept HD; 88%: tacrolimus). Mean calculated GFR was 15­34 mL/min higher in belatacept-treated patients at 1 year. Two cases of posttransplant lymphoproliferative disease and one case of progressive multifocal leukoencephalopathy occurred in belatacept-treated patients. Follow-up beyond month 12 revealed an increase in death and graft loss in another belatacept group (belatacept HD), after which the study was terminated.


Assuntos
Imunoconjugados/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Fígado , Abatacepte , Adulto , Idoso , Esquema de Medicação , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto , Sobrevivência de Enxerto , Hepatite C/mortalidade , Hepatite C/cirurgia , Humanos , Imunoconjugados/administração & dosagem , Terapia de Imunossupressão , Imunossupressores/administração & dosagem , Leucoencefalopatias/complicações , Falência Hepática/mortalidade , Falência Hepática/cirurgia , Transtornos Linfoproliferativos/complicações , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/análogos & derivados , Recidiva , Tacrolimo/administração & dosagem , Resultado do Tratamento
11.
Am J Transplant ; 14(5): 1120-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24731165

RESUMO

Use of grafts from donation after circulatory death (DCD) as a strategy to increase the pool of transplantable livers has been limited due to poorer recipient outcomes compared with donation after brain death (DBD). We examined outcomes of recipients of failed DCD grafts who were selected for relisting with regard to waitlist mortality and patient and graft survival after retransplant. From the Scientific Registry of Transplant Recipients database, we identified 1820 adults who underwent first deceased donor liver transplant January 1, 2004 to June 30, 2011, and were relisted due to graft failure; 12.7% were DCD recipients. Compared with DBD recipients, DCD recipients had better waitlist survival (90-day mortality: 8%, DCD recipients; 14-21%, DBD recipients). Of 950 retransplant patients, 14.5% were prior DCD recipients. Graft survival after second liver transplant was similar for prior DCD (28% graft failure within 1 year) and DBD recipients (30%). Patient survival was slightly better for prior DCD (25% death within 1 year) than DBD recipients (28%). Despite higher overall graft failure and morbidity rates, survival of prior DCD recipients who were selected for relisting and retransplant was not worse than survival of DBD recipients.


Assuntos
Rejeição de Enxerto/mortalidade , Hepatopatias/cirurgia , Transplante de Fígado/mortalidade , Complicações Pós-Operatórias , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Adulto , Morte , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/cirurgia , Sobrevivência de Enxerto , Humanos , Hepatopatias/complicações , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reoperação , Fatores de Risco , Taxa de Sobrevida , Listas de Espera
12.
Am J Transplant ; 12(11): 2901-8, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22822723

RESUMO

Although previous consensus recommendations have helped define patients who would benefit from simultaneous liver-kidney transplantation (SLK), there is a current need to reassess published guidelines for SLK because of continuing increase in proportion of liver transplant candidates with renal dysfunction and ongoing donor organ shortage. The purpose of this consensus meeting was to critically evaluate published and registry data regarding patient and renal outcomes following liver transplantation alone or SLK in liver transplant recipients with renal dysfunction. Modifications to the current guidelines for SLK and a research agenda were proposed.


Assuntos
Transplante de Rim/métodos , Transplante de Fígado/métodos , Guias de Prática Clínica como Assunto , Obtenção de Tecidos e Órgãos , Consenso , Feminino , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos
13.
Transplant Proc ; 53(1): 215-220, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33139039

RESUMO

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is associated with reduced bone density in patients with human immunodeficiency virus, but the effect of TDF on bone density in liver transplant (LT) recipients is unknown. METHODS: We performed a single-center, retrospective study of LT recipients with hepatitis B taking TDF compared to a control group with non-hepatitis B virus viral hepatitis. The primary outcome was reduced bone density, defined as femoral neck or lumbar T-score less than -1. Other outcomes included mean T-score and fractures. RESULTS: Three hundred ninety-three patients were studied: 52 patients in the TDF group and 341 patients in the control group; 64.3% patients in the TDF group had reduced bone density vs 71.4% in the control group (P = .58) before LT, compared to 75% and 81.5% (P = .57), respectively, after LT. Mean posttransplant lumbar T-scores were lower in the TDF group (-1.74 vs -0.75, P = .04). There was no difference between the 2 groups for the other outcomes. In a multivariate Cox proportional hazards model, TDF use did not affect the risk of post-LT reduced bone density (hazard ratio = 0.99; 95% confidence interval, 0.56-1.76; P = .97). CONCLUSION: TDF use was not associated with reduced bone mineral density or increased rates of fractures in LT recipients compared to controls in this study.


Assuntos
Antivirais/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Fraturas Ósseas/epidemiologia , Hepatite B/tratamento farmacológico , Transplante de Fígado , Tenofovir/uso terapêutico , Adulto , Feminino , Vírus da Hepatite B , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
J Clin Invest ; 76(2): 676-84, 1985 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2411761

RESUMO

In these studies, we have used several approaches to systematically explore the contribution of transcellular vesicular transport (transcytosis) to the blood-to-bile movement of inert fluid-phase markers of widely varying molecular weight. First, under steady-state conditions, the perfused rat liver secreted even large markers in appreciable amounts. The bile-to-plasma (B/P) ratio of these different markers, including microperoxidase (B/P ratio = 0.06; mol wt = 1,879), insulin (B/P ratio = 0.09, mol wt = 5,000), horseradish peroxidase (B/P ratio = 0.04, mol wt = 40,000), and dextran (B/P ratio = 0.09, mol wt = 70,000), exhibited no clear ordering based on size alone, and when dextrans of two different sizes (40,000 and 70,000 mol wt) were studied simultaneously, the relative amounts of the two dextran species in bile were the same as in perfusate. Taurocholate administration produced a 71% increase in bile flow but little or no (0-20%) increase in the output of horseradish peroxidase, microperoxidase, inulin, and dextran. Second, under nonsteady-state conditions in which the appearance in or disappearance from bile of selected markers was studied after their abrupt addition to or removal from perfusate, erythritol reached a B/P ratio of 1 within 2 min. Microperoxidase and dextran appeared in bile only after a lag period of approximately 12 min and then slowly approached maximal values, whereas sucrose exhibited kinetically intermediate behavior. A similar pattern was observed after removal of greater than 95% of the marker from the perfusate. Erythritol rapidly reapproached a B/P ratio of 1, whereas the B/P ratio for sucrose, dextran, and microperoxidase fell much more slowly and exceeded 1 for a full 30 min after perfusate washout. Finally, electron microscopy and fluorescence microscopy of cultured hepatocytes demonstrated the presence of horseradish peroxidase and fluorescein-dextran, respectively, in intracellular vesicles, and fractionation of perfused liver homogenates revealed that at least 35-50% of sucrose, inulin, and dextran was associated with subcellular organelles. Collectively, these observations are most compatible with a transcytosis pathway that contributes minimally to the secretion of erythritol, but accounts for a substantial fraction of sucrose secretion and virtually all (greater than 95%) of the blood-to-bile transport of microperoxidase and larger markers. These findings have important implications with respect to current concepts of canalicular bile formation as well as with respect to the conventional use of solutes such as sucrose as markers of canalicular or paracellular pathway permeability.


Assuntos
Bile/metabolismo , Fluoresceína-5-Isotiocianato/análogos & derivados , Fígado/metabolismo , Animais , Transporte Biológico , Dextranos , Eritritol/metabolismo , Fluoresceínas , Fígado/ultraestrutura , Microscopia Eletrônica , Peso Molecular , Perfusão , Peroxidases/metabolismo , Ratos
15.
J Clin Invest ; 83(4): 1225-35, 1989 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2539394

RESUMO

Primary cultures and plasma membrane vesicles were used to characterize Na+ and HCO3- transport by rat hepatocytes. Na+ uptake into hepatocytes was stimulated approximately 10-fold by 25 mM extracellular HCO3-.HCO3--stimulated Na+ uptake was saturable, abolished by 4-acetamido-4'-isothiocyano-2,2'-disulfonic acid stilbene (SITS), and unaffected by amiloride or Cl- removal. Neither propionate nor acetate reproduced this effect of HCO3-. 22Na efflux from preloaded hepatocytes was similarly increased approximately 10-fold by an in greater than out HCO3- concentration gradient. 22Na efflux was also increased by valinomycin and an in greater than out K+ concentration gradient in the presence but not absence of HCO3-. Intracellular pH (pHi) measured with the pH-sensitive fluorochrome 2',7'-bis-(2-carboxyethyl)-5-(and 6-)carboxyfluorescein (BCECF) decreased at a rate of 0.227 (+/- 0.074 SEM) pH units/min when extracellular HCO3- concentration was lowered from 25 to 5 mM at constant PCO2. This intracellular acidification rate was decreased 50-60% in the absence of Na+ or presence of SITS, and was unaffected by amiloride or Cl- removal. Membrane hyperpolarization produced by valinomycin and an in greater than out K+ concentration gradient caused pHi to fall; the rate of fall was decreased 50-70% by Na+ removal or SITS, but not amiloride. An inside positive K+ diffusion potential and a simultaneous out greater than in HCO3- gradient produced a transient 4,4'-diisothiocyano-2,2' disulfonic acid stilbene (DIDS) sensitive, amiloride-insensitive 22Na accumulation in basolateral but not canalicular membrane vesicles. Rat hepatocytes thus exhibit electrogenic basolateral Na+/HCO3- cotransport.


Assuntos
Bicarbonatos/metabolismo , Proteínas de Transporte/metabolismo , Fígado/metabolismo , Canais de Sódio/metabolismo , Sódio/metabolismo , Animais , Transporte Biológico , Membrana Celular/metabolismo , Células Cultivadas , Citosol , Matriz Extracelular/metabolismo , Concentração de Íons de Hidrogênio , Masculino , Potenciais da Membrana , Canais de Potássio/metabolismo , Ratos , Ratos Endogâmicos , Bicarbonato de Sódio , Radioisótopos de Sódio/metabolismo , Trocadores de Sódio-Hidrogênio
16.
Biochim Biophys Acta ; 938(3): 386-94, 1988 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-2450581

RESUMO

Amiloride, a commonly used inhibitor of Na+-H+ exchange, has been shown to exhibit a variety of nonspecific effects. Recently, the more potent amiloride analogs, 5-(N,N-dimethyl)amiloride hydrochloride (DMA) and 5-(N-ethyl-N-isopropyl)amiloride (EIA), have been used to control for the nonspecific effects of the parent compound. In the present study, we have explored the effects of these analogs on Na+/K+-transporting ATPase (Na+/K+-ATPase) and Na+-coupled alanine transport in primary rat hepatocyte cultures and rat liver plasma membranes, and we have compared the effects of these analogs with the effects of amiloride and ouabain. Amiloride, DMA, and EIA increased steady-state Na+ content and inhibited ouabain-sensitive 86Rb+ uptake in a reversible, concentration-dependent, ouabain-like manner, with estimated 50% inhibitory concentrations (IC50) of 3.0.10(-3) M, 5.2.10(-4) M, and 1.2.10(-4) M, respectively. Amiloride, DMA and EIA also inhibited ouabain-sensitive ATP hydrolysis in rat liver plasma membranes with similar potency (IC50 values of 2.2.10(-3) M, 2.2.10(-3) M, and 1.7.10(-4) M, respectively). In separate experiments, amiloride (5.10(-3) M), DMA (10(-3) M), and EIA (2.5.10(-4) M) decreased the uptake into hepatocytes of alanine by 20%, 61%, and 59%, respectively, and further studies with DMA (10(-3) M) demonstrated that this inhibition was largely due to a decrease in the Na+-dependent fraction of alanine uptake. These findings indicate that amiloride, DMA, and EIA inhibit hepatic Na+/K+-ATPase directly, reversibly, and with a relative rank order potency of EIA greater than DMA greater than amiloride. All three compounds also inhibit the hepatic uptake of alanine, and presumably could indirectly inhibit other Na+-coupled transport processes as well.


Assuntos
Alanina/metabolismo , Amilorida/farmacologia , Fígado/metabolismo , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Sódio/metabolismo , Trifosfato de Adenosina/metabolismo , Amilorida/análogos & derivados , Animais , Transporte Biológico/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Células Cultivadas , Canais Iônicos/metabolismo , Fígado/efeitos dos fármacos , Masculino , Ouabaína/farmacologia , Ratos , Ratos Endogâmicos , Radioisótopos de Rubídio/metabolismo , Radioisótopos de Sódio
17.
Neurobiol Aging ; 14(4): 393-5, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8367021

RESUMO

Aged (24-month-old) rats were treated chronically with methanesulfonyl fluoride (MSF), an acetylcholinesterase (AChE) inhibitor with selectivity for central nervous system AChE, or with injection vehicle alone. Twelve 0.22 mg/kg IP injections were given over 4 weeks. MSF rats showed significantly greater speed and accuracy on a 1 trial/day discriminative reward learning task. The chronic MSF treatment resulted in a 56% decrease in brain AChE activity but no discernable locomotor side effects and no liver damage as indicated by aspartate transferase activity.


Assuntos
Envelhecimento/psicologia , Inibidores da Colinesterase/farmacologia , Aprendizagem por Discriminação/efeitos dos fármacos , Recompensa , Sulfonas/farmacologia , Acetilcolinesterase/metabolismo , Animais , Aspartato Aminotransferases/sangue , Encéfalo/enzimologia , Inibidores da Colinesterase/toxicidade , Locomoção/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Esquema de Reforço , Sulfonas/toxicidade
18.
Transplantation ; 62(12): 1788-93, 1996 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-8990364

RESUMO

Renal insufficiency (RI) is a common finding with end-stage liver disease. RI is generally not regarded as a contraindication to liver transplantation. However, the impact of RI on outcome following transplantation and the role of combined liver-kidney transplant are not well understood. The effect of RI on patients with fulminant hepatic failure (FHF) or chronic liver disease (cirrhosis) was investigated using the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Liver Transplantation Database. Patients were analyzed based on the presence of RI, defined as creatinine >1.6 mg/dl, or on dialysis. Patients undergoing liver-kidney transplantation were analyzed separately. For patients with FHF, the RI group had a lower patient survival rate at 1 year (50% vs. 83%, P=0.04) and tended to have a lower graft survival rate (50% vs. 71%). Stay in the intensive care unit (ICU) was prolonged in the RI group but hospital stay was not. Among patients with cirrhosis, RI did not affect patient survival, except for patients on dialysis or those with liver-kidney transplants. One-year patient and graft survival rates were 65% and 60% for the dialysis group, 74% and 70% for the liver-kidney transplant group, 89% and 86% for RI patients not on dialysis, and 89 and 84% for non-RI patients. ICU and hospital stays were prolonged for all of the RI groups compared with the non-RI patients. Patients with RI had higher rates of posttransplant dialysis; however, the differences tended to equalize after 4 weeks. We conclude that RI in FHF and RI requiring dialysis or liver-kidney transplantation in cirrhosis predict lower posttransplant patient and graft survival rates. Patients with RI have longer hospital and ICU stays and an increased need for dialysis, which likely increases the cost of transplantation. Whether liver-kidney transplantation improves outcome and thus represents an appropriate use of cadaver kidneys requires further study.


Assuntos
Transplante de Rim , Transplante de Fígado , Insuficiência Renal/cirurgia , Adulto , Creatinina/sangue , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/fisiologia , Encefalopatia Hepática/cirurgia , Hospitalização , Humanos , Imunossupressores/uso terapêutico , Incidência , Unidades de Terapia Intensiva , Transplante de Rim/imunologia , Transplante de Rim/mortalidade , Tempo de Internação , Transplante de Fígado/imunologia , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Diálise Renal , Insuficiência Renal/terapia , Taxa de Sobrevida
19.
Transplantation ; 66(3): 302-10, 1998 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-9721797

RESUMO

BACKGROUND: Poor graft function early after liver transplantation is an important cause of morbidity and mortality. We defined early allograft dysfunction (EAD) using readily available indices of function and identified donor, graft, and pretransplant recipient factors associated with this outcome. METHODS: This study examined 710 adult recipients of a first, single-organ liver transplantation for non-fulminant liver disease at three United States centers. EAD was defined by the presence of at least one of the following between 2 and 7 days after liver transplantation: serum bilirubin >10 mg/dl, prothrombin time (PT) > or =17 sec, and hepatic encephalopathy. RESULTS: EAD incidence was 23%. Median intensive care unit (ICU) and hospital stays were longer for recipients with EAD than those without (4 days vs. 3 days, P = 0.0001; 24 vs. 15 days, P = 0.0001, respectively). Three-year recipient and graft survival were worse in those with EAD than in those without (68% vs. 83%, P = .0001; 61% vs. 79%, P = 0.0001). A logistic regression model combining donor, graft, and recipient factors predicted EAD better than models examining these factors in isolation. Pretransplant recipient elevations in PT and bilirubin, awaiting a graft in hospital or ICU, donor age > or =50 years, donor hospital stay >3 days, preprocurement acidosis, and cold ischemia time > or =15 hr were independently associated with EAD. CONCLUSION: Recipients who develop EAD have longer ICU and hospital stays and greater mortality than those without. Donor, graft, and recipient risk factors all contribute to the development of EAD. Results of these analyses identify factors that, if modified, may alter the risk of EAD.


Assuntos
Falência Hepática/diagnóstico , Testes de Função Hepática , Transplante de Fígado , Complicações Pós-Operatórias/diagnóstico , Adolescente , Adulto , Bilirrubina/sangue , Cuidados Críticos , Feminino , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/mortalidade , Humanos , Tempo de Internação/estatística & dados numéricos , Falência Hepática/mortalidade , Transplante de Fígado/fisiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
20.
Transplantation ; 61(2): 258-61, 1996 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-8600634

RESUMO

An end-to-end choledochocholedochostomy (CD) over a T tube or a Roux-en-Y choledochojejunostomy (CDJ) have been the standard method of biliary reconstruction following orthotopic liver transplantation (OLTx). The objective of this study was to assess whether or not use of the T tube leads to increased biliary tract complications. Biliary tract complications were categorized as bile leak, stenosis, or obstruction that required therapeutic intervention. OLTx was performed in 161 patients over an 18-month period. Fifty-one patients were excluded from the study leaving a total of 110 patients for evaluation. Fifty-nine had their bile duct reconstructed over a T tube (CD T tube, group I) while the remaining 51 patients underwent bile duct reconstruction without a T tube (CD, group II). No difference was noted between groups I and II in their survival rate, rate of conversion to Roux-en-Y CDJ, or biliary complication rates. Our results indicate that CD (i.e., without a T tube) is both a safe and effective technique to reconstruct the biliary tract following hepatic transplantation. Routine use of a T tube with a CD anastomosis is unnecessary in most liver transplant patients. In addition, the omission of a T tube has reduced the number of radiological procedures performed at our center.


Assuntos
Doenças Biliares/etiologia , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Transplante de Fígado/métodos , Procedimentos Cirúrgicos do Sistema Biliar/métodos , Feminino , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo
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