RESUMO
Steatosis is the most important prognostic histologic feature in the setting of liver procurement. The currently utilized diagnostic methods, including gross evaluation and frozen section examination, have important shortcomings. Novel techniques that offer advantages over the current tools could be of significant practical utility. The aim of this study is to evaluate the accuracy of surface color spectrophotometry in the quantitative assessment of steatosis in a murine model of fatty liver. C57BL/6 mice were divided into a control group receiving normal chow (n = 19), and two steatosis groups receiving high-fat diets for up to 20 weeks-mild steatosis (n = 10) and moderate-to-severe steatosis (n = 19). Mouse liver surfaces were scanned with a hand-held spectrophotometer (CM-600D; Konica-Minolta, Osaka, Japan). Spectral reflectance data and color space values (L*a*b*, XYZ, L*c*h*, RBG, and CMYK) were correlated with histopathologic steatosis evaluation by visual estimate, digital image analysis (DIA), as well as biochemical tissue triglyceride measurement. Spectral reflectance and most color space values were very strongly correlated with histologic assessment of total steatosis, with the best predictor being % reflectance at 700 nm (r = 0.91 [0.88-0.94] for visual assessment, r = 0.92 [0.88-0.95] for DIA of H&E slides, r = 0.92 [0.87-0.95] for DIA of oil-red-O stains, and r = 0.78 [0.63-0.87] for biochemical tissue triglyceride measurement, p < 0.0001 for all). Several spectrophotometric parameters were also independently predictive of large droplet steatosis. In conclusion, hepatic steatosis can accurately be assessed using a portable, commercially available hand-held spectrophotometer device. If similarly accurate in human livers, this technique could be utilized as a point-of-care tool for the quantitation of steatosis, which may be especially valuable in assessing livers during deceased donor organ procurement.
Assuntos
Fígado Gorduroso , Fígado , Espectrofotometria/métodos , Animais , Modelos Animais de Doenças , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/patologia , Técnicas Histológicas , Fígado/diagnóstico por imagem , Fígado/patologia , Transplante de Fígado , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Espectrofotometria/instrumentaçãoRESUMO
BACKGROUND: A number of different molecular interactions data download formats now exist, designed to allow access to these valuable data by diverse user groups. These formats include the PSI-XML and MITAB standard interchange formats developed by Molecular Interaction workgroup of the HUPO-PSI in addition to other, use-specific downloads produced by other resources. The onus is currently on the user to ensure that a piece of software is capable of read/writing all necessary versions of each format. This problem may increase, as data providers strive to meet ever more sophisticated user demands and data types. RESULTS: A collaboration between EMBL-EBI and the University of Cambridge has produced JAMI, a single library to unify standard molecular interaction data formats such as PSI-MI XML and PSI-MITAB. The JAMI free, open-source library enables the development of molecular interaction computational tools and pipelines without the need to produce different versions of software to read different versions of the data formats. CONCLUSION: Software and tools developed on top of the JAMI framework are able to integrate and support both PSI-MI XML and PSI-MITAB. The use of JAMI avoids the requirement to chain conversions between formats in order to reach a desired output format and prevents code and unit test duplication as the code becomes more modular. JAMI's model interfaces are abstracted from the underlying format, hiding the complexity and requirements of each data format from developers using JAMI as a library.
Assuntos
Linguagens de Programação , Software , Estatística como Assunto , Bases de Dados de Proteínas , Humanos , Mapas de Interação de Proteínas , ProteômicaRESUMO
BACKGROUND: Systems biologists study interaction data to understand the behaviour of whole cell systems, and their environment, at a molecular level. In order to effectively achieve this goal, it is critical that researchers have high quality interaction datasets available to them, in a standard data format, and also a suite of tools with which to analyse such data and form experimentally testable hypotheses from them. The PSI-MI XML standard interchange format was initially published in 2004, and expanded in 2007 to enable the download and interchange of molecular interaction data. PSI-XML2.5 was designed to describe experimental data and to date has fulfilled this basic requirement. However, new use cases have arisen that the format cannot properly accommodate. These include data abstracted from more than one publication such as allosteric/cooperative interactions and protein complexes, dynamic interactions and the need to link kinetic and affinity data to specific mutational changes. RESULTS: The Molecular Interaction workgroup of the HUPO-PSI has extended the existing, well-used XML interchange format for molecular interaction data to meet new use cases and enable the capture of new data types, following extensive community consultation. PSI-MI XML3.0 expands the capabilities of the format beyond simple experimental data, with a concomitant update of the tool suite which serves this format. The format has been implemented by key data producers such as the International Molecular Exchange (IMEx) Consortium of protein interaction databases and the Complex Portal. CONCLUSIONS: PSI-MI XML3.0 has been developed by the data producers, data users, tool developers and database providers who constitute the PSI-MI workgroup. This group now actively supports PSI-MI XML2.5 as the main interchange format for experimental data, PSI-MI XML3.0 which additionally handles more complex data types, and the simpler, tab-delimited MITAB2.5, 2.6 and 2.7 for rapid parsing and download.
Assuntos
Mapas de Interação de Proteínas , Proteoma/metabolismo , Proteômica , Bases de Dados de Proteínas , Humanos , Mutação/genética , Biologia de SistemasRESUMO
UNLABELLED: The presence of an intrahepatic cholangiocarcinoma (iCCA) in a cirrhotic liver is a contraindication for liver transplantation in most centers worldwide. Recent investigations have shown that "very early" iCCA (single tumors ≤2 cm) may have acceptable results after liver transplantation. This study further evaluates this finding in a larger international multicenter cohort. The study group was composed of those patients who were transplanted for hepatocellular carcinoma or decompensated cirrhosis and found to have an iCCA at explant pathology. Patients were divided into those with "very early" iCCA and those with "advanced" disease (single tumor >2 cm or multifocal disease). Between January 2000 and December 2013, 81 patients were found to have an iCCA at explant; 33 had separate nodules of iCCA and hepatocellular carcinoma, and 48 had only iCCA (study group). Within the study group, 15/48 (31%) constituted the "very early" iCCA group and 33/48 (69%) the "advanced" group. There were no significant differences between groups in preoperative characteristics. At explant, the median size of the largest tumor was larger in the "advanced" group (3.1 [2.5-4.4] versus 1.6 [1.5-1.8]). After a median follow-up of 35 (13.5-76.4) months, the 1-year, 3-year, and 5-year cumulative risks of recurrence were, respectively, 7%, 18%, and 18% in the very early iCCA group versus 30%, 47%, and 61% in the advanced iCCA group, P = 0.01. The 1-year, 3-year, and 5-year actuarial survival rates were, respectively, 93%, 84%, and 65% in the very early iCCA group versus 79%, 50%, and 45% in the advanced iCCA group, P = 0.02. CONCLUSION: Patients with cirrhosis and very early iCCA may become candidates for liver transplantation; a prospective multicenter clinical trial is needed to further confirm these results. (Hepatology 2016;64:1178-1188).
Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Carcinoma Hepatocelular/cirurgia , Colangiocarcinoma/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Idoso , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
When transplanted simultaneously, the liver allograft has been thought to have an immunoprotective role on other organs; however, detailed analyses in simultaneous heart-liver transplantation (SHLT) have not been done to date. We analyzed patient outcomes and incidence of immune-mediated injury in 22 consecutive SHLT versus 223 isolated heart transplantation (IHT) recipients between January 2004 and December 2013, by reviewing 3912 protocol- and indication-specific cardiac allograft biopsy specimens. Overall survival was similar (86.4%, 86.4%, and 69.1% for SHLT and 93.3%, 84.7%, and 70.0% for IHT at 1, 5, and 10 years; p = 0.83). Despite similar immunosuppression, the incidence of T cell-mediated rejection (TCMR) was lower in SHLT (31.8%) than in IHT (84.8%) (p < 0.0001). Although more SHLT patients had preexisting donor-specific HLA antibody (22.7% versus 8.1%; p = 0.04), the incidence of antibody-mediated rejection was not different in SHLT compared with IHT (4.5% versus 14.8%, p = 0.33). While the left ventricular ejection fraction was comparable in both groups at 5 years, the incidence and severity of cardiac allograft vasculopathy were reduced in the SHLT recipients (42.9% versus 66.8%, p = 0.03). Simultaneously transplanted liver allograft was associated with reduced risk of TCMR (odds ratio [OR] 0.003, 95% confidence interval [CI] 0-0.02; p < 0.0001), antibody-mediated rejection (OR 0.04, 95% CI 0-0.46; p = 0.004), and cardiac allograft vasculopathy (OR 0.26, 95% CI 0.07-0.84; p = 0.02), after adjusting for other risk factors. These data suggest that the incidence of alloimmune injury in the heart allograft is reduced in SHLT recipients.
Assuntos
Aloenxertos/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Transplante de Coração , Transplante de Fígado , Complicações Pós-Operatórias/prevenção & controle , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Cardiopatias/cirurgia , Humanos , Incidência , Hepatopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/imunologia , Prognóstico , Fatores de RiscoRESUMO
Determining risk for recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) is an important clinical need. We assessed consecutive patients who underwent LT for HCC following sequential transarterial chemoembolization (TACE). Treatment response was assessed using modified response evaluation criteria in solid tumors (mRECIST) categories: complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Cox proportional hazard models were used to predict HCC recurrence. One hundred seventy-three patients underwent TACE and imaging to assess response prior to LT. TACE responses were: CR = 23.7%, PR = 24.3%, SD = 27.7% and PD = 24.3%. Five-year HCC recurrence rate was 5.3% in patients responding to TACE (CR/PR), versus 17.6%, among patients who did not respond (SD/PD, p = 0.014). In multivariate analysis, independent pre-LT predictors of recurrence were response to TACE and largest radiologic size of tumor (>3 cm vs. ≤3 cm). HCC recurrence rate for patients with tumor size >3 cm and no response to TACE was 35.8%, compared with 1.9% for patients with tumor size ≤3 cm and response to TACE (p = 0.0007). We conclude that mRECIST criteria and tumor size differentiate patients with high or low likelihood of HCC recurrence after LT. These findings raise the possibility of incorporating response to TACE and largest tumor size to identify patients at highest risk for HCC recurrence.
Assuntos
Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica , Neoplasias Hepáticas/patologia , Idoso , Carcinoma Hepatocelular/terapia , Feminino , Humanos , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , RecidivaRESUMO
To identify genetic risks for obesity and diabetes postliver transplantation (LT), LT recipients underwent genotyping for IL28B rs12979860 (n = 295) and PNPLA3 rs738409 (n = 205) polymorphism in both donors and recipients. The development of obesity and diabetes/impaired fasting glucose (IFG) was determined 1-5 years post-LT. Recipient PNPLA-3 genotype was independently associated with obesity (BMI > 30) at 3 years posttransplant (genotype CC 33.7%, CG 48.3% and GG 82.4%, p = 0.002), with an odds ratio (OR 2.54, CI 1.38-4.66, p = 0.003), associated with the G allele. Diabetes/IFG diagnosed within 5 years posttransplant associated with PNPLA-3 non-CC genotype (HR 1.59, 1.12-2.26, p = 0.010), but not IL28B TT genotype (HR 1.46, 0.94-2.27, p = 0.092). No genotype variable was independently predictive of diabetes/IFG. The combination of PNPLA-3 non-CC and IL28B TT genotype was associated with increased risk of diabetes/IFG compared to PNPLA-3 CC, IL28B non-TT (HR 2.64, CI 1.30-5.39, p = 0.008). Donor genotypes were not associated with any of the outcomes analyzed. In conclusion, PNPLA-3 non-CC genotype is associated with posttransplant obesity but not independently with diabetes/IFG. The lack of donor related risk suggests a peripheral rather than central mechanism of insulin resistance in liver transplant recipients.
Assuntos
Diabetes Mellitus/genética , Interleucinas/genética , Lipase/genética , Transplante de Fígado/efeitos adversos , Proteínas de Membrana/genética , Obesidade/genética , Adulto , Humanos , Resistência à Insulina/genética , Interferons , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Doadores de TecidosRESUMO
Obesity is increasingly common before and after liver transplantation (LT), yet optimal management remains unclear. Our aim was to analyze the effectiveness of a multidisciplinary protocol for obese patients requiring LT, including a noninvasive pretransplant weight loss program, and a combined LT plus sleeve gastrectomy (SG) for obese patients who failed to lose weight prior to LT. Since 2006, all patients referred LT with a BMI > 35 were enrolled. There were 37 patients who achieved weight loss and underwent LT alone, and 7 who underwent LT combined with SG. In those who received LT alone, weight gain to BMI > 35 was seen in 21/34, post-LT diabetes (DM) in 12/34, steatosis in 7/34, with 3 deaths plus 3 grafts losses. In patients undergoing the combined procedure, there were no deaths or graft losses. One patient developed a leak from the gastric staple line, and one had excess weight loss. No patients developed post-LT DM or steatosis, and all had substantial weight loss (mean BMI = 29). Noninvasive pretransplant weight loss was achieved by a majority, though weight gain post-LT was common. Combined LT plus SG resulted in effective weight loss and was associated with fewer post-LT metabolic complications. Long-term follow-up is needed.
Assuntos
Derivação Gástrica/métodos , Falência Hepática/terapia , Transplante de Fígado/métodos , Obesidade/cirurgia , Adulto , Idoso , Índice de Massa Corporal , Endoscopia/métodos , Feminino , Gastrectomia/métodos , Humanos , Falência Hepática/complicações , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Fatores de Risco , Resultado do Tratamento , Redução de PesoRESUMO
The current liver allocation system, introduced in 2002, decreased the importance of waiting time for allocation priorities; the number of active wait-listed candidates and median waiting times were immediately reduced. However, the total number of adult wait-listed candidates has increased since 2002, and median waiting time has increased since 2006. Pretransplant mortality rates have been stable, but the number of candidates withdrawn from the list as being too sick to undergo transplant nearly doubled between 2009 and 2011. Deceased donation rates have remained stable, with an increasing proportion of expanded criteria donors. Living donation has decreased over the past 10 years. Transplant outcomes remain robust, with continuously improving graft survival rates for deceased donor, living donor, and donation after circulatory death livers. Numbers of new and prevalent pediatric candidates on the waiting list have decreased. Pediatric pretransplant mortality has decreased, most dramatically for candidates aged less than 1 year. The transplant rate has increased since 2002, and is highest in candidates aged less than 1 year. Graft survival continues to improve for pediatric recipients of deceased donor and living donor livers. Incidence of acute rejections increases with time after transplant. Posttransplant lymphoproliferative disorder remains an important concern in pediatric recipients.
Assuntos
Transplante de Fígado , Humanos , Imunossupressores/administração & dosagem , Doadores Vivos , Doadores de Tecidos , Listas de EsperaRESUMO
The presence of preformed donor-specific HLA antibodies (DSA) in liver transplant recipients is increasingly recognized; however, the prevalence of DSA and their impact on early allograft function remains unknown. We prospectively followed serum DSA levels of 90 consecutive liver transplant recipients from baseline to 4 months. Twenty recipients (22.2%) had preformed DSA. No antibody-targeting treatments were undertaken. Seven days after transplantation, DSA levels decreased markedly in all but three patients. Day 7 protocol biopsies showed diffuse C4d deposition along the portal stroma, central vein, subendothelial and stromal space in the patients with persistent high DSA levels. The rate of acute cellular rejection was not significantly different in patients with DSA. The transaminase and bilirubin levels remained comparable during the first year despite the presence of DSA. The three patients with persistently high DSA levels continue to have normal allograft function. We conclude that in most cases, DSA disappear after liver transplant, however in rare instances where they persist, there is evidence of complement activation in the liver allograft, without significant clinical impact in the first year.
Assuntos
Autoanticorpos/imunologia , Antígenos HLA/imunologia , Transplante de Fígado , Humanos , Prevalência , Resultado do TratamentoRESUMO
IL28B polymorphisms are strongly associated with response to treatment for HCV infection. IL28B acts on interferon-stimulated genes via the JAK-STAT pathway, which has been implicated in development of insulin resistance. We investigated whether IL28B polymorphisms are associated with posttransplant diabetes mellitus (DM). Consecutive HCV patients who underwent liver transplantation between 1-1995 and 1-2011 were studied. Genotyping of the polymorphism rs12979860 was performed on DNA collected from donors and recipients. Posttransplant DM was screened for by fasting blood glucoses every 1-3 months. Of 221 included patients, 69 developed posttransplant DM (31%). Twenty-two patients with recipient IL28B genotype TT (48%), 25 with IL28B genotype CT (25%) and 22 with IL28B genotype CC (29%) developed posttransplant DM. TT genotype was statistically significantly associated with posttransplant DM over time (log rank p = 0.012 for TT vs. CT and p = 0.045 for TT vs. CC). Multivariate Cox regression analysis correcting for donor age, body mass index, baseline serum glucose, baseline serum cholesterol, recipient age and treated rejection, showed that recipient IL28B genotype TT was independently associated with posttransplant DM (hazard ratio 2.51; 95% confidence interval 1.17-5.40; p = 0.011). We conclude that the risk of developing posttransplant DM is significantly increased in recipients carrying the TT polymorphism of the IL28B gene.
Assuntos
Diabetes Mellitus/etiologia , Hepatite C Crônica/complicações , Interleucinas/genética , Transplante de Fígado/efeitos adversos , Polimorfismo Genético/genética , Complicações Pós-Operatórias , Adulto , Diabetes Mellitus/diagnóstico , Feminino , Seguimentos , Hepacivirus/patogenicidade , Hepatite C Crônica/genética , Hepatite C Crônica/cirurgia , Humanos , Interferon gama/metabolismo , Interferons , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , RNA Viral/genéticaRESUMO
The role of antibody-based immunosuppression in liver transplant recipients remains an area in which prospective trials are needed.
Assuntos
Anticorpos/química , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Transplante de Fígado/efeitos adversos , Anticorpos/uso terapêutico , Ensaios Clínicos como Assunto , Sobrevivência de Enxerto , Humanos , Análise Multivariada , Prevalência , Linfócitos T/metabolismo , Resultado do TratamentoRESUMO
Although mortality rates following liver transplantation (LT) are well described, there is a lack of detailed, prospective studies determining patterns of and risk factors for long-term mortality. We analyzed the multicenter, prospectively obtained The National Institute of Diabetes and Digestive and Kidney Diseases LT Database of 798 transplant recipients from 1990 to 1994 (follow-up 2003). Overall, 327 recipients died. Causes of death >1 year: 28% hepatic, 22% malignancy, 11% cardiovascular, 9% infection, 6% renal failure. Renal-related death increased dramatically over time. Risk factors for death >1 year (univariate): male gender, age/decade, pre-LT diabetes, post-LT diabetes, post-LT hypertension, post-LT renal insufficiency, retransplantation >1 year, pre-LT malignancy, alcoholic disease (ALD) and metabolic liver disease, with similar risks noted for death >5 years. Hepatitis C, retransplantation, post-LT diabetes, hypertension and renal insufficiency were significant risk factors for liver-related death. Cardiac deaths associated with age, male gender, ALD, cryptogenic disease, pre-LT hypertension and post-LT renal insufficiency. In summary, the leading causes of late deaths after transplant were graft failure, malignancy, cardiovascular disease and renal failure. Older age, diabetes and renal insufficiency identified patients at highest risk of poor survival overall. Diligent management of modifiable post-LT factors including diabetes, hypertension and renal insufficiency may impact long-term mortality.
Assuntos
Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Alcoólicos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/etiologia , Diabetes Mellitus/mortalidade , Feminino , Seguimentos , Hepatite C/induzido quimicamente , Hepatite C/etiologia , Hepatite C/mortalidade , Humanos , Hipertensão/induzido quimicamente , Hipertensão/etiologia , Hipertensão/mortalidade , Rim , Transplante de Rim/mortalidade , Fígado , Hepatopatias/etiologia , Hepatopatias/mortalidade , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) , Estudos Prospectivos , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/etiologia , Insuficiência Renal/mortalidade , Fatores de Risco , Resultado do Tratamento , Estados UnidosRESUMO
We aimed to identify recipient, donor and transplant risk factors associated with graft failure and patient mortality following donation after cardiac death (DCD) liver transplantation. These estimates were derived from Scientific Registry of Transplant Recipients data from all US liver-only DCD recipients between September 1, 2001 and April 30, 2009 (n = 1567) and Cox regression techniques. Three years post-DCD liver transplant, 64.9% of recipients were alive with functioning grafts, 13.6% required retransplant and 21.6% died. Significant recipient factors predictive of graft failure included: age ≥ 55 years, male sex, African-American race, HCV positivity, metabolic liver disorder, transplant MELD ≥ 35, hospitalization at transplant and the need for life support at transplant (all, p ≤ 0.05). Donor characteristics included age ≥ 50 years and weight >100 kg (all, p ≤ 0.005). Each hour increase in cold ischemia time (CIT) was associated with 6% higher graft failure rate (HR 1.06, p < 0.001). Donor warm ischemia time ≥ 35 min significantly increased graft failure rates (HR 1.84, p = 0.002). Recipient predictors of mortality were age ≥ 55 years, hospitalization at transplant and retransplantation (all, p ≤ 0.006). Donor weight >100 kg and CIT also increased patient mortality (all, p ≤ 0.035). These findings are useful for transplant surgeons creating DCD liver acceptance protocols.
Assuntos
Morte , Transplante de Fígado/efeitos adversos , Doadores de Tecidos , Adolescente , Adulto , Isquemia Fria , Feminino , Rejeição de Enxerto/epidemiologia , Humanos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Obtenção de Tecidos e Órgãos/métodos , Resultado do Tratamento , Estados Unidos/epidemiologia , Isquemia QuenteRESUMO
In the nontransplant setting diabetes mellitus is a risk factor for disease progression in patients with chronic hepatitis C virus (HCV) infection. The impact of early insulin resistance on the development of advanced fibrosis, even in the absence of clinically apparent diabetes mellitus, is not known. Our aim was to determine whether the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) can be used to identify insulin-resistant patients at risk for rapid fibrosis progression. Cohort study including patients transplanted for chronic HCV between January 1, 1995 and January 1, 2005. One hundred sixty patients were included; 25 patients (16%) were treated for diabetes mellitus and 36 patients (23%) were prediabetic, defined as HOMA-IR >2.5. Multivariate Cox regression analysis showed that insulin resistance (hazard ratio (HR) 2.07; confidence interval (CI) 1.10-3.91, p = 0.024), donor age (HR 1.33;CI 1.08-1.63, p = 0.007) and aspartate aminotransferase (HR 1.03;CI 1.01-1.05, p < 0.001) were significantly associated with a higher probability of developing advanced fibrosis, i.e. Knodell fibrosis stage 3 or 4, whereas steatosis (HR 0.94;CI 0.46-1.92, p = 0.87) and acute cellular rejection (HR 1.72;CI 0.88-3.36, p = 0.111) were not. In conclusion, posttransplant insulin resistance is strongly associated with more severe recurrence of HCV infection. HOMA-IR is an important tool for the identification of insulin resistance among patients at risk for rapid fibrosis progression after liver transplantation for HCV.
Assuntos
Adipocinas/sangue , Hepatite C Crônica/complicações , Resistência à Insulina , Cirrose Hepática/complicações , Transplante de Fígado , Adulto , Estudos de Coortes , Complicações do Diabetes , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Leptina/sangue , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/fisiopatologia , Análise de Regressão , RiscoRESUMO
Liver transplantation numbers in the United States remained constant from 2004 to 2007, while the number of waiting list candidates has trended down. In 2007, the waiting list was at its smallest since 1999, with adults > or =50 years representing the majority of candidates. Noncholestatic cirrhosis was most commonly diagnosed. Most age groups had decreased waiting list death rates; however, children <1 year had the highest death rate. Use of liver allografts from donation after cardiac death (DCD) donors increased in 2007. Model for end-stage liver disease (MELD)/pediatric model for end-stage liver disease (PELD) scores have changed very little since 2002, with MELD/PELD <15 accounting for 75% of the waiting list. Over the same period, the number of transplants for MELD/PELD <15 decreased from 16.4% to 9.8%. Hepatocellular carcinoma exceptions increased slightly. The intestine transplantation waiting list decreased from 2006, with the majority of candidates being children <5 years old. Death rates improved, but remain unacceptably high. Policy changes have been implemented to improve allocation and recovery of intestine grafts to positively impact mortality. In addition to evaluating trends in liver and intestine transplantation, we review in depth, issues related to organ acceptance rates, DCD, living donor transplantation and MELD/PELD exceptions.
Assuntos
Intestinos/transplante , Transplante de Fígado/estatística & dados numéricos , Sistema ABO de Grupos Sanguíneos , Carcinoma Hepatocelular/cirurgia , Criança , Pré-Escolar , Etnicidade , Feminino , Humanos , Lactente , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/mortalidade , Masculino , Grupos Raciais , Taxa de Sobrevida , Sobreviventes , Transplante Homólogo/mortalidade , Transplante Homólogo/estatística & dados numéricos , Estados Unidos/epidemiologia , Listas de EsperaRESUMO
The impact of obesity on outcomes following liver transplantation has been difficult to determine, in part due to the confounding effects of ascites on BMI. We evaluated the impact of pretransplant recipient obesity on outcomes following liver transplantation using the NIDDK Liver Transplantation Database. Pretransplant BMI, corrected for ascites, was categorized as underweight (BMI <18 kg/m(2)), normal weight (BMI 18-25 kg/m(2)), overweight (BMI 25.1-30 kg/m(2)), Class I obese (BMI 30.1-35 kg/m(2)), Class II obese (BMI 35.1-40 kg/m(2)) and Class III obese (BMI >40 kg/m(2)). Primary outcomes were patient and graft survival. Secondary outcomes included days in hospital and days in ICU. Data from 704 adult liver transplant recipients from the NIDDK LTD and a further 609 patients from the Mayo Clinic were analyzed. Early and late patient and graft survival was similar across all BMI categories. Correcting for ascites volume resulted in 11-20% of patients moving into a lower BMI classification. The relative risk for mortality increased by 7% for each liter of ascites removed. We conclude that corrected BMI is not independently predictive of patient or graft survival. Obesity, within the ranges observed in this study, should not be considered to be a contraindication to liver transplantation in the absence of other relative contraindications.
Assuntos
Sobrevivência de Enxerto , Transplante de Fígado/mortalidade , Obesidade/complicações , Ascite/diagnóstico , Ascite/patologia , Índice de Massa Corporal , Peso Corporal , Contraindicações , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
Recurrent hepatitis C virus (HCV) infection is a major cause of morbidity and mortality after liver transplantation for HCV-related end stage liver disease. Although previous studies have shown a short-term effect of interferon-based treatment on fibrosis progression, it is unclear whether this translates to improved graft survival. We evaluated whether treatment of recurrent HCV leads to an improved graft survival. Cohort study included consecutive HCV patients who underwent liver transplantation between 1 January 1995 and 1 January 2005 in the Mayo Clinic, Rochester, MN. Two hundred and fifteen patients were included in the study. During a median follow-up of 4.4 years (interquartile range 2.2-6.6), 165 patients (77%) had biopsy-proven recurrent HCV infection confirmed by serum HCV RNA testing. Seventy-eight patients were treated. There were no differences in MELD-score, fibrosis stage or time towards HCV recurrence between treated and untreated patients at time of recurrence. There was a trend for greater frequency of acute cellular rejection among untreated patients. The incidence of graft failure was lower for patients treated within 6 months of recurrence compared to patients not treated within this time-period (log rank p = 0.002). Time-dependent multivariate Cox regression analysis showed that treatment of recurrent HCV infection was statistically significantly associated with a decreased risk of overall graft failure (hazard ratio 0.34; CI 0.15-0.77, p = 0.009) and a decreased risk of graft failure due to recurrent HCV (hazard ratio 0.24; CI 0.08-0.69, p = 0.008). In conclusion, although a cause and effect relationship cannot be established, treatment of recurrent HCV infection after liver transplantation is associated with a reduced risk of graft failure.
Assuntos
Hepatite C/patologia , Hepatite C/terapia , Interferon-alfa/uso terapêutico , Transplante de Fígado/efeitos adversos , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Antivirais/administração & dosagem , Feminino , Rejeição de Enxerto , Hepatite C/tratamento farmacológico , Humanos , Interferon alfa-2 , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Proteínas Recombinantes , Recidiva , Análise de Regressão , Risco , Resultado do TratamentoRESUMO
BACKGROUND: The aim was to evaluate outcomes in patients with ulcerative colitis complicated by primary sclerosing cholangitis (PSC) who required ileal pouch-anal anastomosis (IPAA) and orthotopic liver transplantation (OLT). METHODS: A retrospective analysis was performed of 32 patients undergoing both IPAA and OLT between 1980 and 2006. Data were collected regarding demographics, indication for surgery, postoperative complications, and outcome of IPAA and OLT. RESULTS: Thirty-day mortality after either procedure was nil. The median preoperative Model for End-stage Liver Disease (MELD) score for the group with initial IPAA was 8 (range 6-20) and the postoperative score was 11 (range 6-19). At 1 and 10 years, 32 and 26 of the 32 liver grafts had survived, and 31 and 30 of the 32 pouches, respectively. Fourteen patients require daily medical therapy for chronic pouchitis. At a median follow-up of 3.6 (range 0.2-16.2) years after the second of two procedures, responding patients reported a median of 5.5 stools per day and 2 stools per night. CONCLUSION: IPAA and OLT are feasible and safe in patients requiring both procedures for ulcerative colitis and PSC. Functional outcomes are stable over time, despite an increased risk of chronic pouchitis.
Assuntos
Canal Anal/cirurgia , Colangite Esclerosante/complicações , Colite Ulcerativa/complicações , Bolsas Cólicas , Transplante de Fígado , Adolescente , Adulto , Anastomose Cirúrgica , Colite Ulcerativa/cirurgia , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pouchite/etiologia , Resultado do TratamentoRESUMO
A 28-day dietary study was conducted in Hsd:SD rats to evaluate the safety of PureLo, a non-caloric powdered concentrate of the Chinese fruit Luo Han Guo, which derives its sweetening properties from triterpene glycosides called mogrosides. Groups of 20 rats (10/sex/group) were fed diets containing 0, 10,000, 30,000, or 100,000 ppm PureLo for 28 days (OECD, Redbook 2000). PureLo was well tolerated and produced no significant adverse effects. Reduced body weight and body weight gain in high-dose animals of both sexes were related to sporadic reductions in food consumption; there were no overall differences in feed efficiency. Statistically significant changes in clinical chemistry (decreased bilirubin, increased total protein) and relative organ weights of liver, adrenals, ovaries and/or testes, and epididymides were not correlated with any histopathological findings and were not considered adverse. Although a few clinical and pathological findings suggest possible treatment-related effects, particularly in the high-dose group, these findings were transient, not dose-dependent, non-adverse, inconsistent, occurred only in one sex, and/or not supported by histopathological findings. Under the conditions of this study and based on the toxicological endpoints evaluated, the NOAEL for PureLo was 100,000 ppm in the diet, the highest level tested, equivalent to 7.07 and 7.48 g/kg bw/day for male and female rats, respectively.