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1.
Am J Transplant ; 22 Suppl 2: 204-309, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35266621

RESUMEN

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.


Asunto(s)
COVID-19 , Obtención de Tejidos y Órganos , Adulto , COVID-19/epidemiología , Niño , Femenino , Supervivencia de Injerto , Humanos , Hígado , Masculino , Pandemias , SARS-CoV-2 , Donantes de Tejidos , Estados Unidos/epidemiología , Listas de Espera
2.
Am J Transplant ; 21 Suppl 2: 208-315, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33595192

RESUMEN

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.


Asunto(s)
Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Obtención de Tejidos y Órganos , Anciano , Enfermedad Hepática en Estado Terminal/cirugía , Femenino , Supervivencia de Injerto , Humanos , Donadores Vivos , Masculino , Índice de Severidad de la Enfermedad , Donantes de Tejidos , Listas de Espera
3.
Am J Transplant ; 20 Suppl s1: 542-568, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31898411

RESUMEN

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.


Asunto(s)
Transmisión de Enfermedad Infecciosa/prevención & control , Selección de Donante/organización & administración , Hepacivirus , Hepatitis C Crónica/epidemiología , Trasplante de Hígado/estadística & datos numéricos , Donantes de Tejidos/provisión & distribución , Listas de Espera , Hepatitis C Crónica/transmisión , Hepatitis C Crónica/virología , Humanos
4.
Am J Transplant ; 20 Suppl s1: 193-299, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31898413

RESUMEN

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.


Asunto(s)
Trasplante de Hígado/estadística & datos numéricos , Sistema de Registros , Asignación de Recursos , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/métodos , Listas de Espera , Supervivencia de Injerto , Humanos , Estados Unidos
5.
Am J Transplant ; 19 Suppl 2: 184-283, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30811890

RESUMEN

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.


Asunto(s)
Supervivencia de Injerto , Trasplante de Hígado/métodos , Sistema de Registros/estadística & datos numéricos , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/métodos , Informes Anuales como Asunto , Humanos , Estados Unidos , Listas de Espera
6.
Am J Transplant ; 18 Suppl 1: 172-253, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29292603

RESUMEN

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.


Asunto(s)
Informes Anuales como Asunto , Supervivencia de Injerto , Trasplante de Hígado , Obtención de Tejidos y Órganos , Listas de Espera , Humanos , Sistema de Registros , Donantes de Tejidos , Estados Unidos
7.
Am J Transplant ; 17 Suppl 1: 174-251, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-28052604

RESUMEN

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.


Asunto(s)
Informes Anuales como Asunto , Supervivencia de Injerto , Trasplante de Hígado , Asignación de Recursos , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/métodos , Humanos , Inmunosupresores , Resultado del Tratamiento , Estados Unidos , Listas de Espera
8.
Am J Transplant ; 16 Suppl 2: 69-98, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26755264

RESUMEN

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.


Asunto(s)
Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Hígado/métodos , Trasplante de Hígado/estadística & datos numéricos , Adolescente , Adulto , Anciano , Niño , Preescolar , Enfermedad Hepática en Estado Terminal/epidemiología , Supervivencia de Injerto , Humanos , Inmunosupresores/uso terapéutico , Donadores Vivos , Persona de Mediana Edad , Factores de Tiempo , Donantes de Tejidos , Resultado del Tratamiento , Estados Unidos , Listas de Espera , Adulto Joven
9.
Am J Transplant ; 15 Suppl 2: 1-28, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25626341

RESUMEN

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.


Asunto(s)
Informes Anuales como Asunto , Hepatopatías/cirugía , Trasplante de Hígado/estadística & datos numéricos , Asignación de Recursos , Donantes de Tejidos , Listas de Espera , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Supervivencia de Injerto , Humanos , Lactante , Recién Nacido , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Readmisión del Paciente , Tasa de Supervivencia , Resultado del Tratamiento , Estados Unidos , Adulto Joven
10.
Am J Transplant ; 14(5): 1120-8, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24731165

RESUMEN

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.


Asunto(s)
Rechazo de Injerto/mortalidad , Hepatopatías/cirugía , Trasplante de Hígado/mortalidad , Complicaciones Posoperatorias , Donantes de Tejidos , Obtención de Tejidos y Órganos/estadística & datos numéricos , Adulto , Muerte , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Rechazo de Injerto/cirugía , Supervivencia de Injerto , Humanos , Hepatopatías/complicaciones , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Pronóstico , Reoperación , Factores de Riesgo , Tasa de Supervivencia , Listas de Espera
11.
Am J Transplant ; 14(8): 1817-27, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25041339

RESUMEN

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.


Asunto(s)
Inmunoconjugados/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante de Hígado , Abatacept , Adulto , Anciano , Esquema de Medicación , Femenino , Tasa de Filtración Glomerular , Rechazo de Injerto , Supervivencia de Injerto , Hepatitis C/mortalidad , Hepatitis C/cirugía , Humanos , Inmunoconjugados/administración & dosificación , Terapia de Inmunosupresión , Inmunosupresores/administración & dosificación , Leucoencefalopatías/complicaciones , Fallo Hepático/mortalidad , Fallo Hepático/cirugía , Trastornos Linfoproliferativos/complicaciones , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/análogos & derivados , Recurrencia , Tacrolimus/administración & dosificación , Resultado del Tratamiento
12.
Am J Transplant ; 12(11): 2901-8, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22822723

RESUMEN

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.


Asunto(s)
Trasplante de Riñón/métodos , Trasplante de Hígado/métodos , Guías de Práctica Clínica como Asunto , Obtención de Tejidos y Órganos , Consenso , Femenino , Estudios de Seguimiento , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/mortalidad , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Masculino , Medición de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Estados Unidos
13.
Transplant Proc ; 53(1): 215-220, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33139039

RESUMEN

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.


Asunto(s)
Antivirales/uso terapéutico , Densidad Ósea/efectos de los fármacos , Fracturas Óseas/epidemiología , Hepatitis B/tratamiento farmacológico , Trasplante de Hígado , Tenofovir/uso terapéutico , Adulto , Femenino , Virus de la Hepatitis B , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
14.
J Clin Invest ; 76(2): 676-84, 1985 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-2411761

RESUMEN

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.


Asunto(s)
Bilis/metabolismo , Fluoresceína-5-Isotiocianato/análogos & derivados , Hígado/metabolismo , Animales , Transporte Biológico , Dextranos , Eritritol/metabolismo , Fluoresceínas , Hígado/ultraestructura , Microscopía Electrónica , Peso Molecular , Perfusión , Peroxidasas/metabolismo , Ratas
15.
J Clin Invest ; 83(4): 1225-35, 1989 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-2539394

RESUMEN

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.


Asunto(s)
Bicarbonatos/metabolismo , Proteínas Portadoras/metabolismo , Hígado/metabolismo , Canales de Sodio/metabolismo , Sodio/metabolismo , Animales , Transporte Biológico , Membrana Celular/metabolismo , Células Cultivadas , Citosol , Matriz Extracelular/metabolismo , Concentración de Iones de Hidrógeno , Masculino , Potenciales de la Membrana , Canales de Potasio/metabolismo , Ratas , Ratas Endogámicas , Bicarbonato de Sodio , Radioisótopos de Sodio/metabolismo , Intercambiadores de Sodio-Hidrógeno
16.
Biochim Biophys Acta ; 938(3): 386-94, 1988 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-2450581

RESUMEN

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.


Asunto(s)
Alanina/metabolismo , Amilorida/farmacología , Hígado/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidores , Sodio/metabolismo , Adenosina Trifosfato/metabolismo , Amilorida/análogos & derivados , Animales , Transporte Biológico/efectos de los fármacos , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Células Cultivadas , Canales Iónicos/metabolismo , Hígado/efectos de los fármacos , Masculino , Ouabaína/farmacología , Ratas , Ratas Endogámicas , Radioisótopos de Rubidio/metabolismo , Radioisótopos de Sodio
17.
Neurobiol Aging ; 14(4): 393-5, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8367021

RESUMEN

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.


Asunto(s)
Envejecimiento/psicología , Inhibidores de la Colinesterasa/farmacología , Aprendizaje Discriminativo/efectos de los fármacos , Recompensa , Sulfonas/farmacología , Acetilcolinesterasa/metabolismo , Animales , Aspartato Aminotransferasas/sangre , Encéfalo/enzimología , Inhibidores de la Colinesterasa/toxicidad , Locomoción/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Esquema de Refuerzo , Sulfonas/toxicidad
18.
Transplantation ; 62(12): 1788-93, 1996 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-8990364

RESUMEN

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.


Asunto(s)
Trasplante de Riñón , Trasplante de Hígado , Insuficiencia Renal/cirugía , Adulto , Creatinina/sangre , Femenino , Rechazo de Injerto/epidemiología , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/fisiología , Encefalopatía Hepática/cirugía , Hospitalización , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Unidades de Cuidados Intensivos , Trasplante de Riñón/inmunología , Trasplante de Riñón/mortalidad , Tiempo de Internación , Trasplante de Hígado/inmunología , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Diálisis Renal , Insuficiencia Renal/terapia , Tasa de Supervivencia
19.
Transplantation ; 66(3): 302-10, 1998 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-9721797

RESUMEN

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.


Asunto(s)
Fallo Hepático/diagnóstico , Pruebas de Función Hepática , Trasplante de Hígado , Complicaciones Posoperatorias/diagnóstico , Adolescente , Adulto , Bilirrubina/sangre , Cuidados Críticos , Femenino , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/mortalidad , Humanos , Tiempo de Internación/estadística & datos numéricos , Fallo Hepático/mortalidad , Trasplante de Hígado/fisiología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/mortalidad , Factores de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento
20.
Transplantation ; 63(8): 1074-9, 1997 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-9133467

RESUMEN

BACKGROUND: The transjugular intrahepatic portosystemic shunt (TIPS) is an important treatment for complications of portal hypertension. As some authors have suggested that TIPS may facilitate liver transplantation technically, the objective of this study was to determine the impact of TIPS on the liver transplant operation and its outcome. METHODS: The analysis was designed as a retrospective cohort study using a multicenter database. Fifty-five patients with TIPS were matched with 55 controls on the basis of 10 pretransplant laboratory, clinical, and demographic features. TIPS patients and control patients were compared with regard to duration of surgery, intraoperative blood product usage, liver and renal function, volume of ascites, survival, and hospital stay. For confirmatory purposes, a parallel analysis using linear regression methods was performed. RESULTS: By matched analysis, TIPS patients had less ascites at surgery (mean 0.9+/-0.20 vs. 2.2+/-0.37 L, P=0.005) and a slightly shorter time from incision to cross-clamp (mean 2.1+/-0.10 vs. 2.5+/-0.15 hr, P=0.03). However, there were not significant differences for total operative time (mean 6.0+/-0.17 vs. 6.3+/-0.25 hr, P=1.00), blood product usage, or any other outcome variable. Regression analysis confirmed these results. CONCLUSIONS: TIPS does not significantly impact the course of liver transplantation surgery. Therefore, preoperative portal decompression solely to facilitate liver transplantation is not an appropriate indication for TIPS.


Asunto(s)
Trasplante de Hígado/fisiología , Derivación Portosistémica Intrahepática Transyugular/normas , Estudios de Cohortes , Estudios de Evaluación como Asunto , Hematócrito , Humanos , Pruebas de Función Renal , Pruebas de Función Hepática , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Análisis de Regresión , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo
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