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1.
Ann Gastroenterol Surg ; 8(3): 383-393, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38707230

RESUMO

Background: We aimed to identify the characteristics of new-onset diabetes after liver transplantation (LT) (NODAT) and investigate its impacts on post-transplant outcomes. Methods: Adult LT patients between 2014 and 2020 who used tacrolimus as initial immunosuppression and survived 3 months at least were evaluated. Patients who developed NODAT within 3 months after LT were classified as NODAT group. Also, patients were further classified as history of diabetes before LT (PHDBT) and non-diabetes (ND) groups. Patient characteristics, post-LT outcomes, and cardiovascular and/or pulmonary complications were compared. Results: A total of 83, 225, and 263 patients were classified into NODAT, PHDBT, and ND groups. The proportion of cholestatic liver disease and rejection within 90 days were higher in NODAT group. Mean serum tacrolimus concentration trough level in the first week after LT was 7.12, 6.12, and 6.12 ng/mL (p < 0.001). Duration of corticosteroids was significantly longer in NODAT compared to PHDBD or ND (416, 289, and 228 days, p < 0.001). Three-year graft and patient survival were significantly worse in NODAT than ND (80.5% vs. 95.0%, p < 0.001: 82.0% vs. 95.4%, p < 0.001) but similar to PHDBT. Adjusted risks of 3-year graft loss and patient death using Cox regression analysis were significantly higher in NODAT compared to ND (adjusted hazard ratio [aHR] 3.41, p = 0.004; aHR 3.61, p = 0.004). Incidence rates of cardiovascular or pulmonary complications after LT in NODAT were significantly higher than ND but similar to PHDBT. Conclusion: Higher initial tacrolimus concentration and early rejection might be risk factors for NODAT. NODAT was associated with worse post-transplant outcomes.

2.
Am J Transplant ; 22(3): 909-926, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34780106

RESUMO

To extend previous molecular analyses of rejection in liver transplant biopsies in the INTERLIVER study (ClinicalTrials.gov #NCT03193151), the present study aimed to define the gene expression selective for parenchymal injury, fibrosis, and steatohepatitis. We analyzed genome-wide microarray measurements from 337 liver transplant biopsies from 13 centers. We examined expression of genes previously annotated as increased in injury and fibrosis using principal component analysis (PCA). PC1 reflected parenchymal injury and related inflammation in the early posttransplant period, slowly regressing over many months. PC2 separated early injury from late fibrosis. Positive PC3 identified a distinct mildly inflamed state correlating with histologic steatohepatitis. Injury PCs correlated with liver function and histologic abnormalities. A classifier trained on histologic steatohepatitis predicted histologic steatohepatitis with cross-validated AUC = 0.83, and was associated with pathways reflecting metabolic abnormalities distinct from fibrosis. PC2 predicted histologic fibrosis (AUC = 0.80), as did a molecular fibrosis classifier (AUC = 0.74). The fibrosis classifier correlated with matrix remodeling pathways with minimal overlap with those selective for steatohepatitis, although some biopsies had both. Genome-wide assessment of liver transplant biopsies can not only detect molecular changes induced by rejection but also those correlating with parenchymal injury, steatohepatitis, and fibrosis, offering potential insights into disease mechanisms for primary diseases.


Assuntos
Transplante de Fígado , Fígado , Biópsia , Fígado Gorduroso , Fibrose , Rejeição de Enxerto , Humanos , Fígado/patologia , Transplante de Fígado/efeitos adversos , Fenótipo
3.
Oncotarget ; 12(3): 185-198, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33613846

RESUMO

Hepatocellular carcinoma (HCC) is the most common primary liver tumor worldwide. Current medical therapy for HCC has limited efficacy. The present study tests the hypothesis that human cerebral endothelial cell-derived exosomes carrying elevated miR-214 (hCEC-Exo-214) can amplify the efficacy of anti-cancer drugs on HCC cells. Treatment of HepG2 and Hep3B cells with hCEC-Exo-214 in combination with anti-cancer agents, oxaliplatin or sorafenib, significantly reduced cancer cell viability and invasion compared with monotherapy with either drug. Additionally, the therapeutic effect of the combination therapy was detected in primary tumor cells derived from patients with HCC. The ability of hCEC-Exo-214 in sensitizing HCC cells to anti-cancer drugs was specific, in that combination therapy did not affect the viability and invasion of human liver epithelial cells and non-cancer primary cells. Furthermore, compared to monotherapy with oxaliplatin and sorafenib, hCEC-Exo-214 in combination with either drug substantially reduced protein levels of P-glycoprotein (P-gp) and splicing factor 3B subunit 3 (SF3B3) in HCC cells. P-gp and SF3B3 are among miR-214 target genes and are known to mediate drug resistance and cancer cell proliferation, respectively. In conclusion, the present in vitro study provides evidence that hCEC-Exo-214 significantly enhances the anti-tumor efficacy of oxaliplatin and sorafenib on HCC cells.

4.
Transplantation ; 105(12): 2571-2578, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33449608

RESUMO

BACKGROUND: Graft-versus-host disease (GVHD) after liver transplantation (LT) is a rare but serious complication. The aim of this study is to identify risk factors, including immunosuppressive regimens, for mortality due to GVHD (fatal GVHD). METHODS: Using data from the Organ Procurement and Transplantation Network and United Network for Organ Sharing registry, 77 416 adult patients who underwent LT between 2003 and 2018 were assessed. Risk factors for fatal GVHD were analyzed by focusing on induction and maintenance immunosuppression regimens. RESULTS: The incidence of fatal GVHD was 0.2% (121 of 77 416), of whom 105 (87%) died within 180 d and 13 (11%) died between 181 d and 1 y. Median survival after LT was 68.0 (49.5-125.5) d. Recipient age minus donor age >20 y (hazard ratio [HR], 2.57; P < 0.001) and basiliximab induction (HR, 1.69; P = 0.018) were independent risk factors for fatal GVHD. Maintenance therapy with mycophenolate mofetil (MMF) was associated with a decrease in fatal GVHD (HR, 0.51; P = 0.001). In an increased risk cohort of patients with recipient-donor age discrepancy >20 y, MMF use was associated with a 50% decline in fatal GVHD (HR, 0.50; P < 0.001). CONCLUSIONS: Recipient age minus donor age >20 y remains a significant risk factor for fatal GVHD. The risk of fatal GVHD significantly increases in association with basiliximab induction and decreases with MMF maintenance. These associations were pronounced in patients with recipient minus donor age >20 y. These results emphasize the importance of donor age and individualized immunosuppression regimens on the risk of fatal GVHD.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Fígado , Adulto , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Transplante de Fígado/efeitos adversos , Ácido Micofenólico , Fatores de Risco
5.
Am J Transplant ; 21(3): 1100-1112, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32794649

RESUMO

The success of direct-acting antiviral (DAA) therapy has led to near-universal cure for patients chronically infected with hepatitis C virus (HCV) and improved post-liver transplant (LT) outcomes. We investigated the trends and outcomes of retransplantation in HCV and non-HCV patients before and after the introduction of DAA. Adult patients who underwent re-LT were identified in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Multiorgan transplants and patients with >2 total LTs were excluded. Two eras were defined: pre-DAA (2009-2012) and post-DAA (2014-2017). A total of 2112 re-LT patients were eligible (HCV: n = 499 pre-DAA and n = 322 post-DAA; non-HCV: n = 547 pre-DAA and n = 744 post-DAA). HCV patients had both improved graft and patient survival after re-LT in the post-DAA era. One-year graft survival was 69.8% pre-DAA and 83.8% post-DAA (P < .001). One-year patient survival was 73.1% pre-DAA and 86.2% post-DAA (P < .001). Graft and patient survival was similar between eras for non-HCV patients. When adjusted, the post-DAA era represented an independent positive predictive factor for graft and patient survival (hazard ratio [HR]: 0.67; P = .005, and HR: 0.65; P = .004) only in HCV patients. The positive post-DAA era effect was observed only in HCV patients with first graft loss due to disease recurrence (HR: 0.31; P = .002, HR 0.32; P = .003, respectively). Among HCV patients, receiving a re-LT in the post-DAA era was associated with improved patient and graft survival.


Assuntos
Hepatite C Crônica , Hepatite C , Adulto , Antivirais/uso terapêutico , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C/cirurgia , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/cirurgia , Humanos , Reoperação , Estudos Retrospectivos , Estados Unidos/epidemiologia
7.
Ann Surg Oncol ; 27(13): 5209-5221, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32495286

RESUMO

BACKGROUND: Based on favorable outcomes reported by experienced centers, perihilar cholangiocarcinoma (Ph-CCA) has become an accepted indication for liver transplantation (LT). What is less clear is if the reported outcomes have been reproduced nationwide in the US. OBJECTIVE: The aim of this study was to evaluate post-transplant outcomes in patients with Ph-CCA and to determine prognostic factors. METHODS: Patients who underwent LT with Model for End-stage Liver Disease exception scores for Ph-CCA between 2010 and 2017 were evaluated. Transplant centers were classified into well- and less-experienced groups: Group 1 [well-experienced (≥ 6 LTs), 7 centers]; Group 2 [less-experienced (< 6 LTs), 23 centers]. Post-transplant mortality due to all-cause and recurrence of Ph-CCA were set as endpoints. RESULTS: Post-transplant outcomes were significantly better in Group 1 than in Group 2, with 1-, 3-, and 5-year patient survival rates of 91.8%, 56.9%, and 45.8%, versus 65.6%, 48.8%, and 26.0%, respectively. Group 2 showed a significantly higher risk of 1-, 3-, and 5-year all-cause mortality and 1-year mortality associated with Ph-CCA recurrence. Center experience was an independent risk factor for post-transplant mortality. In intention-to-treat analysis, a positive prognostic effect of LT was significant and LT decreased the mortality risk by 86% in the well-experienced group [hazard ratio (HR) 0.14, p < 0.001], whereas this effect was not observed in the less-experienced group (HR 1.35, p = 0.47). CONCLUSIONS: Risk of recurrence of malignancy and mortality was significantly higher in the less-experienced center group. Center effects on post-transplant outcomes in patients with Ph-CCA should be recognized, and the introduction of center approval for LT for Ph-CCA may be justified to achieve comparable outcomes between centers.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Doença Hepática Terminal , Tumor de Klatskin , Transplante de Fígado , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/cirurgia , Humanos , Tumor de Klatskin/cirurgia , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
8.
Hepatology ; 72(6): 2051-2062, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32157711

RESUMO

BACKGROUND AND AIMS: Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) policy mandates a 6-month waiting period before exception scores are granted to liver transplant candidates with hepatocellular carcinoma (HCC). This study aims to evaluate waitlist and posttransplant outcomes in patients with HCC, before and after implementation of the 6-month waiting rule. APPROACH AND RESULTS: We examined two groups from the UNOS registry: Group 1 (pre-6-month rule) consisted of patients registered as transplant candidates with HCC from January 1, 2013, to October 7, 2015 (n = 4,814); group 2 (post-6-month rule) consisted of patients registered from October 8, 2015, to June 30, 2018 (n = 3,287). As expected, the transplant probability was higher in the first 6 months after listing in group 1 than group 2 at 42.0% versus 6.3% (P < 0.001). However, the 6-month waitlist mortality/dropout rate was lower in group 2 at 1.2% than group 1 at 4.1% (P < 0.001). To assess regional parity of transplant, UNOS regions were categorized into three groups based on Model for End-Stage Liver Disease score at transplant: lower-score (regions 3, 10, and 11), middle-score (1, 2, 6, 8, and 9), and higher-score region groups (4, 5, and 7). Outcomes were compared from the time exception points were given, which we defined as conditional waitlist outcomes. Conditional waitlist mortality/dropout decreased, and transplant probability increased in all region groups, but the benefits of the policy were more pronounced in the higher and middle-score groups, compared with the lower-score group. The decline in waitlist mortality/dropout was only significant in the high Model for End-Stage Liver Disease group (P < 0.001). No effect was observed on posttransplant mortality or percent of patients within Milan criteria on explant. CONCLUSIONS: The HCC policy change was associated with decreased waitlist mortality/dropout and increased transplant probability. The policy helped to decrease but did not eliminate regional disparities in transplant opportunity without an effect on posttransplant outcomes.


Assuntos
Carcinoma Hepatocelular/terapia , Doença Hepática Terminal/terapia , Neoplasias Hepáticas/terapia , Transplante de Fígado/estatística & dados numéricos , Listas de Espera/mortalidade , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/patologia , Feminino , Geografia , Implementação de Plano de Saúde , Acessibilidade aos Serviços de Saúde/normas , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Transplante de Fígado/normas , Masculino , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Políticas , Probabilidade , Avaliação de Programas e Projetos de Saúde , Sistema de Registros/estatística & dados numéricos , Índice de Gravidade de Doença , Fatores de Tempo , Tempo para o Tratamento/normas , Obtenção de Tecidos e Órgãos/normas , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
9.
Am J Transplant ; 20(8): 2156-2172, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32090446

RESUMO

Molecular diagnosis of rejection is emerging in kidney, heart, and lung transplant biopsies and could offer insights for liver transplant biopsies. We measured gene expression by microarrays in 235 liver transplant biopsies from 10 centers. Unsupervised archetypal analysis based on expression of previously annotated rejection-related transcripts identified 4 groups: normal "R1normal " (N = 129), T cell-mediated rejection (TCMR) "R2TCMR " (N = 37), early injury "R3injury " (N = 61), and fibrosis "R4late " (N = 8). Groups differed in median time posttransplant, for example, R3injury 99 days vs R4late 3117 days. R2TCMR biopsies expressed typical TCMR-related transcripts, for example, intense IFNG-induced effects. R3injury displayed increased expression of parenchymal injury transcripts (eg, hypoxia-inducible factor EGLN1). R4late biopsies showed immunoglobulin transcripts and injury-related transcripts. R2TCMR correlated with histologic rejection although with many discrepancies, and R4late with fibrosis. R2TCMR , R3injury , and R4late correlated with liver function abnormalities. Supervised classifiers trained on histologic rejection showed less agreement with histology than unsupervised R2TCMR scores. No confirmed cases of clinical antibody-mediated rejection (ABMR) were present in the population, and strategies that previously revealed ABMR in kidney and heart transplants failed to reveal a liver ABMR phenotype. In conclusion, molecular analysis of liver transplant biopsies detects rejection, has the potential to resolve ambiguities, and could assist with immunosuppressive management.


Assuntos
Transplante de Coração , Transplante de Rim , Transplante de Fígado , Biópsia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/genética , Transplante de Fígado/efeitos adversos
10.
Clin Gastroenterol Hepatol ; 17(13): 2759-2768.e5, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31004758

RESUMO

BACKGROUND & AIMS: An increasing number of patients with non-alcoholic steatohepatitis (NASH) require liver transplantation. We compared outcomes of patients with liver diseases of different etiologies (NASH, hepatitis C virus [HCV]-associated liver disease, and alcohol-associated liver disease [ALD]). METHODS: We analyzed data from the United Network for Organ Sharing registry on 6344 patients who underwent liver transplantation for NASH, 17,037 for cirrhosis from chronic HCV infection, and 9279 for ALD. We collected data from patients who underwent liver transplantation during the following time periods: 2008-2010, 2011-2013, 2014-2015, 2016-2017. We compared outcomes of different groups using Cox regression models, adjusting for donor and recipient characteristics. RESULTS: For patients who underwent liver transplantation during 2016-2017, a significantly lower proportion of patients with NASH survived for 1 year after transplantation than patients with HCV (P = .004) or ALD (P < .001). During this time period, the adjusted risk of death within 1 year was significantly higher for patients with NASH than with ALD (hazard ratio, 1.37; P = .03), regardless of the presence of hepatocellular carcinoma. The effects of increasing age were greatest among patients with NASH: compared to patients younger than 50 years, hazard ratios for overall mortality were 1.31 for patients 50-59 years (P = .02), 1.66 for patients 60-64 years (P < .001), 2.08 for patients 65-69 years (P < .001), and 2.66 and for patients and ≥70 years (P < .001). Mortality from cardiovascular or cerebrovascular disease(s) was highest among patients with NASH, accounting for 11.5% of deaths, compared to 7.0% of deaths in patients with HCV infection and 9.6% in patients with ALD (P < .001). CONCLUSIONS: In an analysis of data from patients who underwent liver transplantation during 2016-2017, we found the risk of death within 1 year after transplant was higher among patients with NASH than HCV-associated liver disease or ALD. Risk of death increased with age, and patients with NASH have a higher risk of death from cardiovascular or cerebrovascular disease.


Assuntos
Hepatite C Crônica/cirurgia , Cirrose Hepática/cirurgia , Hepatopatias Alcoólicas/cirurgia , Transplante de Fígado , Mortalidade , Hepatopatia Gordurosa não Alcoólica/cirurgia , Fatores Etários , Idoso , Carcinoma Hepatocelular/cirurgia , Doenças Cardiovasculares/mortalidade , Causas de Morte , Transtornos Cerebrovasculares/mortalidade , Isquemia Fria , Feminino , Hepatite C Crônica/complicações , Humanos , Avaliação de Estado de Karnofsky , Cirrose Hepática/etiologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco
11.
Hepatology ; 61(3): 895-904, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25099130

RESUMO

UNLABELLED: Although experimental evidence has indicated that ischemia-reperfusion (I/R) injury of the liver stimulates growth of micrometastases and adhesion of tumor cells, the clinical impact of I/R injury on recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has not been fully investigated. To study this issue, we conducted a retrospective review of the medical records of 391 patients from two transplant centers who underwent LT for HCC. Ischemia times along with other tumor/recipient variables were analyzed as risk factors for recurrence of HCC. Subgroup analysis focused on patients with HCC who had pathologically proven vascular invasion (VI) because of the associated increased risk of micrometastasis. Recurrence occurred in 60 patients (15.3%) with median time to recurrence of 0.9 years (range, 40 days-4.6 years). Cumulative recurrence curves according to cold ischemia time (CIT) at 2-hour intervals and warm ischemia time (WIT) at 10-minute intervals showed that CIT>10 hours and WIT>50 minutes were associated with significantly increased recurrence (P=0.015 and 0.036, respectively). Multivariate Cox's regression analysis identified prolonged cold (>10 hours; P=0.03; hazard ratio [HR]=1.9) and warm (>50 minutes; P=0.003; HR=2.84) ischemia times as independent risk factors for HCC recurrence, along with tumor factors, including poor differentiation, micro- and macrovacular invasion, exceeding Milan criteria, and alpha-fetoprotein>200 ng/mL. Prolonged CIT (P=0.04; HR=2.24) and WIT (P=0.001; HR=5.1) were also significantly associated with early (within 1 year) recurrence. In the subgroup analysis, prolonged CIT (P=0.01; HR=2.6) and WIT (P=0.01; HR=3.23) were independent risk factors for recurrence in patients with VI, whereas there was no association between ischemia times and HCC recurrence in patients with no VI. CONCLUSION: Reducing ischemia time may be a useful strategy to decrease HCC recurrence after LT, especially in those with other risk factors.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Fígado/irrigação sanguínea , Recidiva Local de Neoplasia/prevenção & controle , Traumatismo por Reperfusão/complicações , Transfusão de Sangue , Feminino , Humanos , Masculino , Fatores de Tempo
12.
Gastroenterology ; 148(1): 100-107.e1, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25261839

RESUMO

BACKGROUND & AIMS: Patients with detectable hepatitis C virus (HCV) RNA at the time of liver transplantation universally experience recurrent HCV infection. Antiviral treatment before transplantation can prevent HCV recurrence, but existing interferon-based regimens are poorly tolerated and are either ineffective or contraindicated in most patients. We performed a trial to determine whether sofosbuvir and ribavirin treatment before liver transplantation could prevent HCV recurrence afterward. METHODS: In a phase 2, open-label study, 61 patients with HCV of any genotype and cirrhosis (Child-Turcotte-Pugh score, ≤7) who were on waitlists for liver transplantation for hepatocellular carcinoma, received up to 48 weeks of sofosbuvir (400 mg) and ribavirin before liver transplantation. The primary end point was the proportion of patients with HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients with this HCV-RNA level at their last measurement before transplantation. RESULTS: Sixty-one patients received sofosbuvir and ribavirin, and 46 received transplanted livers. The per-protocol efficacy population consisted of 43 patients who had HCV-RNA level less than 25 IU/mL at the time of transplantation. Of these 43 patients, 30 (70%) had a post-transplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died (2 from nonfunction of the primary graft and 1 from complications of hepatic artery thrombosis). Of all 61 patients given sofosbuvir and ribavirin, 49% had a post-transplantation virologic response. Recurrence was related inversely to the number of consecutive days of undetectable HCV RNA before transplantation. The most frequently reported adverse events were fatigue (in 38% of patients), headache (23%), and anemia (21%). CONCLUSIONS: Administration of sofosbuvir and ribavirin before liver transplantation can prevent post-transplant HCV recurrence. ClinicalTrials.gov: NCT01559844.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/cirurgia , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Ribavirina/uso terapêutico , Uridina Monofosfato/análogos & derivados , Idoso , Antivirais/efeitos adversos , Biomarcadores/sangue , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Quimioterapia Combinada , Europa (Continente) , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/patogenicidade , Hepatite C/complicações , Hepatite C/diagnóstico , Hepatite C/mortalidade , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Cirrose Hepática/virologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Projetos Piloto , RNA Viral/sangue , Recidiva , Ribavirina/efeitos adversos , Sofosbuvir , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Uridina Monofosfato/efeitos adversos , Uridina Monofosfato/uso terapêutico , Carga Viral , Listas de Espera
13.
Transplantation ; 97(6): 694-701, 2014 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-24637868

RESUMO

BACKGROUND: Absolute lymphocyte count (ALC) is considered a surrogate marker for the level of immunosuppression and nutritional status of patients and a prognostic factor for survival and recurrence in several cancers. The aim of this study was to investigate the prognostic value of peritransplant ALC for the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT). METHODS: HCC patients who underwent LT between 2000 and 2010 were evaluated. Exclusion criteria were combined HCC and cholangiocarcinoma. Peritransplant ALCs (before LT and 2 weeks and 1 month after LT) were analyzed along with tumor, operative, and donor characteristics to identify risk factors for the recurrence of HCC. RESULTS: HCC developed in 27 of the 173 LT patients investigated for risk factors (15.6%). The median time to recurrence was 1.14 years. Low ALCs before and after LT were associated with a higher recurrence rate in a continuous manner (before LT: hazard ratio=1.12, P=0.003; 2 weeks after LT: hazard ratio=1.14, P=0.008; 1 month after LT: hazard ratio=1.06, P=0.055) (increased risk per 100/µL down). On multivariate Cox regression analysis, peritransplant persistent lymphopenia (<1000/µL before LT and <500/µL at 2 weeks and 1 month after LT) was an independent risk factor for cancer recurrence (hazard ratio=7.05, P<0.001), along with tumor characteristics. CONCLUSION: Peritransplant lymphopenia is a powerful prognostic factor for the recurrence of HCC after LT, which suggests that maintaining ALCs in LT patients might improve cancer outcome.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Linfopenia/etiologia , Recidiva Local de Neoplasia , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Contagem de Linfócitos , Linfopenia/sangue , Linfopenia/diagnóstico , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
15.
Liver Transpl ; 19(7): 675-89, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23775875

RESUMO

Mycophenolate mofetil (MMF) and sirolimus (SRL) have been used for calcineurin inhibitor (CNI) minimization to reduce nephrotoxicity following liver transplantation. In this prospective, open-label, multicenter study, patients undergoing transplantation from July 2005 to June 2007 who were maintained on MMF/CNI were randomized 4 to 12 weeks after transplantation to receive MMF/SRL (n = 148) or continue MMF/CNI (n = 145) and included in the intent-to-treat population. The primary efficacy endpoints were the mean percentage change in the calculated glomerular filtration rate (GFR) and a composite of biopsy-proven acute rejection (BPAR), graft lost, death, and lost to follow-up 12 months after transplantation. Patients were followed for a median of 519 days after randomization. MMF/SRL was associated with a significantly greater renal function improvement from baseline with a mean percentage change in GFR of 19.7 ± 40.6 (versus 1.2 ± 39.9 for MMF/CNI, P = 0.0012). The composite endpoint demonstrated the noninferiority of MMF/SRL versus MMF/CNI (16.4% versus 15.4%, 90% confidence interval = -7.1% to 9.0%). The incidence of BPAR was significantly greater with MMF/SRL (12.2%) versus MMF/CNI (4.1%, P = 0.02). Graft loss (including death) occurred in 3.4% of the MMF/SRL-treated patients and in 8.3% of the MMF/CNI-treated patients (P = 0.04). Malignancy-related deaths were less frequent with MMF/SRL. Adverse events caused withdrawal for 34.2% of the MMF/SRL-treated patients and for 24.1% of the MMF/CNI-treated patients (P = 0.06). The use of MMF/SRL is an option for liver transplant recipients who can benefit from improved renal function but is associated with an increased risk of rejection (but not graft loss).


Assuntos
Imunossupressores/administração & dosagem , Nefropatias/prevenção & controle , Transplante de Fígado/métodos , Ácido Micofenólico/análogos & derivados , Néfrons/cirurgia , Sirolimo/administração & dosagem , Adulto , Idoso , Biópsia , Inibidores de Calcineurina , Esquema de Medicação , Feminino , Taxa de Filtração Glomerular , Humanos , Terapia de Imunossupressão , Incidência , Nefropatias/complicações , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
Cancer Epidemiol Biomarkers Prev ; 19(4): 1066-73, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20332260

RESUMO

BACKGROUND: Chronic infection with hepatitis C virus (HCV) confers increased risk for chronic renal disease, and numerous reports suggest an association with renal cell carcinoma (RCC), a cancer with rapidly rising global incidence. We sought to determine whether HCV infection confers an increased risk for developing RCC. METHODS: With the use of administrative data from a large, integrated, and ethnically diverse healthcare system, we did a cohort study of 67,063 HCV-tested patients between 1997 and 2006 who were followed for the development of RCC until April 2008. RESULTS: A search of the health system cancer registry for patients with the diagnosis of kidney cancer showed that RCC was diagnosed in 0.6% (17 of 3,057) of HCV-positive patients versus 0.3% (177 of 64,006) of HCV-negative patients. The mean age at RCC diagnosis was much younger in HCV-positive individuals (54 versus 63; P < 0.001). The univariate hazard ratio for RCC among HCV patients was 2.20 (95% confidence interval, 1.32-3.67; P = 0.0025). In a multivariate model that included the risk factors age, African-American race, male gender, and chronic kidney disease, the overall hazard ratio for RCC among HCV patients was 1.77 (95% confidence interval, 1.05-2.98; P = 0.0313). CONCLUSION: Chronic HCV infection confers a risk for the development of RCC. IMPACT: Clinicians should consider newly identified renal lesions in patients with chronic HCV infection with a heightened suspicion for neoplasm, and newly diagnosed cases of RCC may require more careful surveillance for the presence of HCV infection. Additional studies are required to confirm these findings and to explore potential mechanisms of oncogenesis.


Assuntos
Carcinoma de Células Renais/complicações , Hepatite C Crônica/complicações , Neoplasias Renais/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/virologia , Estudos de Coortes , Feminino , Hepatite C Crônica/epidemiologia , Humanos , Neoplasias Renais/epidemiologia , Neoplasias Renais/virologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
19.
J Gastrointest Surg ; 9(5): 672-8, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15862262

RESUMO

Variations in donor and recipient arterial anatomy frequently present challenges for surgeons when attempting to establish proper arterial inflow during liver transplantation. We reviewed our data on 233 adult primary liver transplants, conducted from January 1996 through December 2001, to determine the impact of these variations on the outcomes after liver transplantation. Twenty-four (10.3%) arterial complications were encountered at a mean of 2.27 months after transplant. Carrel patches for the anastomoses were not used in 33 patients (14%), which had no relation to arterial complications (P = 0.7). Sixty-one donors (26.2%) had at least one aberrant artery, which had no relation to arterial complications. However, use of donor celiac artery for anastomosis was significantly associated with higher arterial complications (16% versus other choices, P = 0.03). Furthermore, use of common hepatic recipient artery was associated with higher arterial complications (16%, P = 0.03). There were 58 total biliary complications (24.8%). Biliary complications were associated with the presence of arterial complications (P = 0.01). In conclusion, aberrant donor arterial anatomy was not associated with an increased rate of arterial complications; however, choice of location of arterial anastomosis may be a significant factor. Biliary complications were associated with arterial complications.


Assuntos
Artéria Hepática/anormalidades , Transplante de Fígado/métodos , Complicações Pós-Operatórias/prevenção & controle , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Anastomose Cirúrgica , Estudos de Coortes , Feminino , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Artéria Hepática/cirurgia , Humanos , Circulação Hepática/fisiologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Medição de Risco , Doadores de Tecidos , Resultado do Tratamento
20.
Curr Opin Gastroenterol ; 19(3): 259-63, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-15703566

RESUMO

Over the last 20 years dramatic improvements in liver transplantation have given children and adults a greater than 80% chance of long-term survival. The year 2002 marked a dramatic change in the system for allocating livers from a model based both on medical criteria (Child-Turcotte-Pugh) and waiting time to a system based solely on medical urgency model of end-stage liver disease (MELD). Further attempts to increase organ availability were seen in the continued increase in living donor transplants. Attention was directed both at recipient outcome and on morbidity and safety for the donor. Despite continued advances in the technical outcomes of liver transplantation, recurrent viral disease and malignancy remain major challenges.

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