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1.
Hepatol Commun ; 6(7): 1803-1812, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35220693

RESUMO

High-grade portal vein thrombosis (PVT) is often considered to be a technically challenging scenario for liver transplantation (LT) and in some centers a relative contraindication. This study compares patients with chronic obliterative PVT who underwent portal vein recanalization-transjugular intrahepatic portosystemic shunt (PVR-TIPS) and subsequent LT to those with partial nonocclusive PVT who underwent LT without an intervention. This institutional review board-approved study analyzed 49 patients with cirrhosis with PVT from 2000 to 2020 at our institution. Patients were divided into two groups, those that received PVR-TIPS due to anticipated surgical challenges from chronic obliterative PVT and those who did not because of partial PVT. Demographic data and long-term outcomes were compared. A total of 35 patients received PVR-TIPS while 14 did not, with all receiving LT. Patients with PVR-TIPS had a higher Yerdel score and frequency of cavernoma than those that did not. PVR-TIPS was effective in decreasing portosystemic gradient (16 down to 8 mm HG; p < 0.05). Both groups allowed for end-to-end anastomoses in >90% of cases. However, veno-veno bypass was used significantly more in patients who did not receive PVR-TIPS. Additionally, patients without PVR-TIPS required significantly more intraoperative red blood cells. Overall survival was not different between groups. PVR-TIPS demonstrated efficacy in resolving PVT and allowed for end-to-end portal vein anastomoses. PVR-TIPS is a viable treatment option for chronic obliterative PVT with or without cavernoma that simplifies the surgical aspects of LT.


Assuntos
Hemangioma Cavernoso , Transplante de Fígado , Derivação Portossistêmica Transjugular Intra-Hepática , Trombose Venosa , Hemangioma Cavernoso/complicações , Humanos , Transplante de Fígado/efeitos adversos , Veia Porta/cirurgia , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Resultado do Tratamento , Trombose Venosa/cirurgia
2.
Am J Transplant ; 22(2): 532-540, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34510731

RESUMO

Donor-derived cell-free DNA (dd-cfDNA) has been evaluated as a rejection marker in organ transplantation. This study sought to assess the utility of dd-cfDNA to diagnose graft injury in liver transplant recipients (LTR) and as a predictive biomarker prior to different causes of graft dysfunction. Plasma from single and multicenter LTR cohorts was analyzed for dd-cfDNA. Phenotypes of treated biopsy-proven acute rejection (AR, N = 57), normal function (TX, N = 94), and acute dysfunction no rejection (ADNR; N = 68) were divided into training and test sets. In the training set, dd-cfDNA was significantly different between AR versus TX (AUC 0.95, 5.3% cutoff) and AR versus ADNR (AUC 0.71, 20.4% cutoff). Using these cutoffs in the test set, the accuracy and NPV were 87% and 100% (AR vs. TX) and 66.7% and 87.8% (AR vs. ADNR). Blood samples collected serially from LTR demonstrated incremental elevations in dd-cfDNA prior to the onset of graft dysfunction (AR > ADNR), but not in TX. Dd-cfDNA also decreased following treatment of rejection. In conclusion, the serial elevation of dd-cfDNA identifies pre-clinical graft injury in the context of normal liver function tests and is greatest in rejection. This biomarker may help detect early signs of graft injury and rejection to inform LTR management strategies.


Assuntos
Ácidos Nucleicos Livres , Transplante de Rim , Transplante de Fígado , Biomarcadores , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/genética , Humanos , Transplante de Fígado/efeitos adversos , Doadores de Tecidos , Transplantados
3.
Clin J Am Soc Nephrol ; 16(10): 1539-1551, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34620649

RESUMO

BACKGROUND AND OBJECTIVES: Subclinical acute rejection is associated with poor outcomes in kidney transplant recipients. As an alternative to surveillance biopsies, noninvasive screening has been established with a blood gene expression profile. Donor-derived cellfree DNA (cfDNA) has been used to detect rejection in patients with allograft dysfunction but not tested extensively in stable patients. We hypothesized that we could complement noninvasive diagnostic performance for subclinical rejection by combining a donor-derived cfDNA and a gene expression profile assay. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a post hoc analysis of simultaneous blood gene expression profile and donor-derived cfDNA assays in 428 samples paired with surveillance biopsies from 208 subjects enrolled in an observational clinical trial (Clinical Trials in Organ Transplantation-08). Assay results were analyzed as binary variables, and then, their continuous scores were combined using logistic regression. The performance of each assay alone and in combination was compared. RESULTS: For diagnosing subclinical rejection, the gene expression profile demonstrated a negative predictive value of 82%, a positive predictive value of 47%, a balanced accuracy of 64%, and an area under the receiver operating curve of 0.75. The donor-derived cfDNA assay showed similar negative predictive value (84%), positive predictive value (56%), balanced accuracy (68%), and area under the receiver operating curve (0.72). When both assays were negative, negative predictive value increased to 88%. When both assays were positive, positive predictive value increased to 81%. Combining assays using multivariable logistic regression, area under the receiver operating curve was 0.81, significantly higher than the gene expression profile (P<0.001) or donor-derived cfDNA alone (P=0.006). Notably, when cases were separated on the basis of rejection type, the gene expression profile was significantly better at detecting cellular rejection (area under the receiver operating curve, 0.80 versus 0.62; P=0.001), whereas the donor-derived cfDNA was significantly better at detecting antibody-mediated rejection (area under the receiver operating curve, 0.84 versus 0.71; P=0.003). CONCLUSIONS: A combination of blood-based biomarkers can improve detection and provide less invasive monitoring for subclinical rejection. In this study, the gene expression profile detected more cellular rejection, whereas donor-derived cfDNA detected more antibody-mediated rejection.


Assuntos
Ácidos Nucleicos Livres/sangue , DNA/sangue , Perfilação da Expressão Gênica , Rejeição de Enxerto/diagnóstico , Transplante de Rim/efeitos adversos , Doadores de Tecidos , Transcriptoma , Adulto , Doenças Assintomáticas , Biomarcadores/sangue , Biópsia , Ácidos Nucleicos Livres/genética , DNA/genética , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/genética , Rejeição de Enxerto/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Resultado do Tratamento , Estados Unidos , Adulto Jovem
4.
Cardiovasc Intervent Radiol ; 44(7): 1070-1080, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33825060

RESUMO

PURPOSE: To evaluate hepatocellular carcinoma (HCC) treatment allocation, deviation from BCLC first-treatment recommendation, and outcomes following multidisciplinary, individualized approach. METHODS: Treatment-naïve HCC discussed at multidisciplinary tumor board (MDT) between 2010 and 2013 were included to allow minimum 5 years of follow-up. MDT first-treatment recommendation (resection, transplant, ablation, transarterial radioembolization (Y90), transarterial chemoembolization, sorafenib, palliation) was documented, as were subsequent treatments. Overall survival (OS) analyses were performed on an intention-to-treat (ITT) basis, stratified by BCLC stage. RESULTS: Three hundred and twenty-one patients were treated in the 4-year period. Median age was 62 years, predominantly male (73%), hepatitis C (41%), and Y90 initial treatment (52%). There was a 76% rate of BCLC-discordant first-treatment. Median OS was not reached (57% alive at 10 years), 51.0 months, 25.4 months and 13.4 months for BCLC stages A, B, C and D, respectively. CONCLUSION: Deviation from BCLC guidelines was very common when individualized, MDT treatment recommendations were made. This approach yielded expected OS in BCLC A, and exceeded general guideline expectations for BCLC B, C and D. These results suggest that while guidelines are helpful, implementing a more personalized approach that incorporates center expertise, patient-specific characteristics, and the known multi-directional treatment allocation process, improves patient outcomes.


Assuntos
Algoritmos , Antineoplásicos/uso terapêutico , Braquiterapia/métodos , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Guias de Prática Clínica como Assunto , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Resultado do Tratamento
6.
Transplant Proc ; 52(10): 3085-3089, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32576474

RESUMO

An e-mail-based market research survey focused on high-volume US adult transplant centers was developed and implemented to assess surveillance based on United Network for Organ Sharing/Scientific Registry of Transplant Recipients data: 51 to 100 transplants, 101 to 200 transplants, and more than 200 transplants. Eighty-three centers responded to the survey. Respondent centers represented 13,837/21,167 (65%) of the total kidney transplants in 2018. In total, 38/83 (46%) centers reported the use of surveillance biopsies-20 centers in all patients and 18 in select patients. Surveillance biopsies were performed in 37% (7/19) of centers performing 51 to 100 transplants annually, in 44% (15/34) doing 101 to 200 transplants, and in 53% (16/30) of centers doing more than 200 transplants. Of the 20 centers doing surveillance biopsies in all patients, 17/20 (85%) perform more than 100 annual transplants, and 3/20 (15%) perform less than 100 annual transplants. Of the 45 centers not currently doing surveillance biopsies, 13 (29%) used surveillance biopsies in the past; discontinuation was primarily due to patient inconvenience, adverse events, and cost. Using survey percentages, it is estimated that surveillance biopsies are performed in approximately 34% of kidney transplant recipients and that 74% of all surveillance biopsies occur in centers performing more than 100 kidney transplants per year.


Assuntos
Biópsia , Nefropatias/diagnóstico , Transplante de Rim , Padrões de Prática Médica , Transplantes/patologia , Adulto , Humanos , Rim/patologia , Inquéritos e Questionários , Estados Unidos
7.
Kidney Int ; 98(1): 147-158, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32471635

RESUMO

Cytomegalovirus (CMV) reactivation from latently infected donor organs post-transplantation and its dissemination cause significant comorbidities in transplant recipients. Transplant-induced inflammation combined with chronic immunosuppression has been thought to provoke CMV reactivation and dissemination, although sequential events in this process have not been studied. Here, we investigated this process in a high-risk donor CMV-positive to recipient CMV-negative allogeneic murine kidney transplantation model. Recipients were either treated with indefinite immunosuppression or tolerized in a donor-specific manner. Untreated recipients served as controls. Kidney allografts from both immunosuppressed and tolerized recipients showed minimal alloimmunity-mediated graft inflammation and normal function for up to day 60 post-transplantation. However, despite the absence of such inflammation in the immunosuppressed and tolerized groups, CMV reactivation in the donor positive kidney allograft was readily observed. Interestingly, subsequent CMV replication and dissemination to distant organs only occurred in immunosuppressed recipients in which CMV-specific CD8 T cells were functionally impaired; whereas in tolerized recipients, host anti-viral immunity was well-preserved and CMV dissemination was effectively prevented. Thus, our studies uncoupled CMV reactivation from its dissemination, and underscore the potential role of robust transplantation tolerance in preventing CMV diseases following allogeneic kidney transplantation.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Transplante de Rim , Muromegalovirus , Animais , Citomegalovirus , Tolerância Imunológica , Rim , Transplante de Rim/efeitos adversos , Camundongos , Tolerância ao Transplante , Ativação Viral
8.
Qual Life Res ; 29(9): 2355-2374, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32285345

RESUMO

PURPOSE: Living donor kidney transplant (LDKT) imparts the best graft and patient survival for most end-stage kidney disease (ESKD) patients. Yet, there remains variation in post-LDKT health-related quality of life (HRQOL). Improved understanding of post-LDKT HRQOL can help identify patients for interventions to maximize the benefit of LDKT. METHODS: For 477 LDKT recipients transplanted between 11/2007 and 08/2016, we assessed physical, mental, social, and kidney-targeted HRQOL pre-LDKT, as well as 3 and 12 months post-operatively using the SF-36, Kidney Disease Quality of Life-Short Form (KDQOL-SF), and the Functional Assessment of Cancer Therapy-Kidney Symptom Index 19 item version (FKSI-19). We then examined trajectories of each HRQOL domain using latent growth curve models (LGCMs). We also examined associations between decline in HRQOL from 3 months to 12 months post-LDKT and death censored graft failure (DCGF) using Cox regression. RESULTS: Large magnitude effects (d > 0.80) were observed from pre- to post-LDKT change on the SF-36 Vitality scale (d = 0.81) and the KDQOL-SF Burden of Kidney Disease (d = 1.05). Older age and smaller pre- to post-LDKT decreases in serum creatinine were associated with smaller improvements on many HRQOL scales across all domains in LGCMs. Higher DCGF rates were associated with worse physical [e.g., SF-36 PCSoblique hazard ratio (HR) 1.18; 95% CI 1.01-1.38], mental (KDQOL-SF Cognitive Function HR 1.27; 95% CI 1.00-1.62), and kidney-targeted (FKSI-19 HR: 1.18; 95% CI 1.00-1.38) HRQOL domains. CONCLUSION: Clinical HRQOL monitoring may help identify patients who are most likely to have failing grafts and who would benefit from post-LDKT intervention.


Assuntos
Nível de Saúde , Transplante de Rim/psicologia , Qualidade de Vida/psicologia , Transplantados/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Rim/cirurgia , Falência Renal Crônica/terapia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Psicometria , Adulto Jovem
10.
Hepatology ; 71(5): 1775-1786, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31509263

RESUMO

BACKGROUND AND AIMS: A high proportion of patients develop chronic kidney disease (CKD) after liver transplantation (LT). We aimed to develop clinical/protein models to predict future glomerular filtration rate (GFR) deterioration in this population. APPROACH AND RESULTS: In independent multicenter discovery (CTOT14) and single-center validation (BUMC) cohorts, we analyzed kidney injury proteins in serum/plasma samples at month 3 after LT in recipients with preserved GFR who demonstrated subsequent GFR deterioration versus preservation by year 1 and year 5 in the BUMC cohort. In CTOT14, we also examined correlations between serial protein levels and GFR over the first year. A month 3 predictive model was constructed from clinical and protein level variables using the CTOT14 cohort (n = 60). Levels of ß-2 microglobulin and CD40 antigen and presence of hepatitis C virus (HCV) infection predicted early (year 1) GFR deterioration (area under the curve [AUC], 0.814). We observed excellent validation of this model (AUC, 0.801) in the BUMC cohort (n = 50) who had both early and late (year 5) GFR deterioration. At an optimal threshold, the model had the following performance characteristics in CTOT14 and BUMC, respectively: accuracy (0.75, 0.8), sensitivity (0.71, 0.67), specificity (0.78, 0.88), positive predictive value (0.74, 0.75), and negative predictive value (0.76, 0.82). In the serial CTOT14 analysis, several proteins, including ß-2 microglobulin and CD40, correlated with GFR changes over the first year. CONCLUSIONS: We have validated a clinical/protein model (PRESERVE) that early after LT can predict future renal deterioration versus preservation with high accuracy. This model may help select recipients at higher risk for subsequent CKD for early, proactive renal sparing strategies.


Assuntos
Taxa de Filtração Glomerular , Rim/fisiopatologia , Transplante de Fígado/efeitos adversos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/etiologia , Biomarcadores/sangue , Antígenos CD40/sangue , Estudos de Coortes , Feminino , Hepatite C/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Valor Preditivo dos Testes , Insuficiência Renal Crônica/sangue
11.
Transplantation ; 104(7): 1413-1418, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31644488

RESUMO

BACKGROUND: The vast majority of patients with cirrhosis have low Model for End-Stage Liver Disease-Sodium (MELD-Na) scores; however, the ability for the MELD-Na score to predict patient outcomes at low scores is unclear. METHODS: Adult patients in a multicenter, Chicago-wide database of medical records with International Classification of Disease, Ninth Edition codes of cirrhosis and without a history of hepatocellular carcinoma were included. Records were linked with the state death registry, and death certificates were manually reviewed. Deaths were classified as "liver-related," "non-liver-related," and "non-descript" as adjudicated by a panel comprised of a transplant surgeon, a hepatologist, and an internist. A sensitivity analysis was performed where patients with hepatocellular carcinoma were included. RESULTS: Among 7922 identified patients, 3999 patients had MELD-Na scores that were never higher than 15. In total, 2137 (27%) patients died during the study period with higher mortality rates for the patients in the high MELD-Na group (19.4 (41.6%) versus 4.1 (12.6%) per 100 person-y, P < 0.001). The high MELD-Na group died of a liver-related cause in 1142 out of 1632 (70%) as compared to 240 out of 505 (47.5%) deaths in the low MELD-Na group. There was no difference in the distribution of subcategory of liver-related death between low and high MELD-Na groups. Among subclassification of liver-related deaths, the most common cause of death was "Infectious" in both groups. CONCLUSIONS: Despite persistently low MELD-Na scores, patients with cirrhosis still experience high rates of liver-related mortality.


Assuntos
Doença Hepática Terminal/mortalidade , Cirrose Hepática/mortalidade , Índice de Gravidade de Doença , Sódio/sangue , Listas de Espera/mortalidade , Adulto , Idoso , Causas de Morte , Chicago/epidemiologia , Atestado de Óbito , Progressão da Doença , Doença Hepática Terminal/sangue , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/patologia , Feminino , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Transplante de Fígado/normas , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Prognóstico , Medição de Risco/estatística & dados numéricos , Fatores de Tempo
12.
J Gen Virol ; 100(12): 1680-1694, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31647403

RESUMO

CD34+ myeloid lineage progenitor cells are an important reservoir of latent human cytomegalovirus (HCMV), and differentiation to macrophages or dendritic cells (DCs) is known to cause reactivation of latent virus. Due to its species-specificity, murine models have been used to study mouse CMV (MCMV) latency and reactivation in vivo. While previous studies have shown that MCMV genomic DNA can be detected in the bone marrow (BM) of latently infected mice, the identity of these cells has not been defined. Therefore, we sought to identify and enrich for cellular sites of MCMV latency in the BM haematopoietic system, and to explore the potential for establishing an in vitro model for reactivation of latent MCMV. We studied the kinetics and cellular characteristics of acute infection and establishment of latency in the BM of mice. We found that while MCMV can infect a broad range of haematopoietic BM cells (BMCs), latent virus is only detectable in haematopoietic stem cells (HSCs), myeloid progenitor cells, monocytes and DC-enriched cell subsets. Using three separate approaches, MCMV reactivation was detected in association with differentiation into DC-enriched BMCs cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) followed by lipopolysaccharide (LPS) treatment. In summary, we have defined the kinetics and cellular profile of MCMV infection followed by the natural establishment of latency in vivo in the mouse BM haematopoietic system, including the haematopoietic phenotypes of cells that are permissive to acute infection, establish and harbour detectable latent virus, and can be stimulated to reactivate following DC enrichment and differentiation, followed by treatment with LPS.


Assuntos
Células da Medula Óssea/virologia , Diferenciação Celular , Infecções por Citomegalovirus/virologia , Citomegalovirus/fisiologia , Ativação Viral , Latência Viral , Animais , Biomarcadores , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/virologia , Interações Hospedeiro-Patógeno , Interleucina-4/farmacologia , Cinética , Camundongos , Células Mieloides/efeitos dos fármacos , Células Mieloides/metabolismo , Células Mieloides/virologia , Tropismo Viral , Replicação Viral
13.
Cancers (Basel) ; 11(6)2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31238514

RESUMO

Introduction: We compared the efficacy of the ALBI (albumin-bilirubin) score to the established Child-Pugh (CP) grade in hepatocellular carcinoma (HCC) patients treated with yttrium-90 radioembolization (Y90). We further assessed the individual contributions of albumin and bilirubin to survival prediction. Methods: 1000 consecutive HCC patients treated with Y90 were included. Overall survival (OS) was assessed using Kaplan Meier analysis. Sub-stratification analyses were performed using CP and ALBI and in subgroups determined by United Network for Organ Sharing (UNOS) or Barcelona Clinic Liver Cancer (BCLC) staging. The independent impact (hazard ratio (HR)) of ALBI, CP, albumin, and bilirubin on survival was assessed using Cox proportional hazards analysis. Results: Median OS for ALBI 1, 2, and 3 grades was 46.7, 19.1, and 8.8 months, respectively. The HR for death for ALBI 2 vs. ALBI 1 was 3.39 (1.75-6.57); ALBI 3 vs. ALBI 1 was 7.58 (3.89-14.79); and the c-index was 0.623. Median OS for CP A, B, and C was 21.7, 11.3, and 6.0 months, respectively. The HR for death for CP B vs. CP A was 2.04 (1.71-2.43); CP C vs. CP A was 3.27 (2.08-5.14); and the c-index was 0.616. Stratified OS showed unique prognostic groups identified by ALBI within CP-B and CP-C. Median OS for albumin grades 1, 2, and 3 was 46.0, 17.1, and 9.1 months, respectively. Median OS for bilirubin grades 1, 2, and 3 was 15.6, 21.0, and 5.8 months, respectively. The HR for death for albumin 2 vs. 1 was 2.48 (1.81-3.41); albumin 3 vs. 1 was 4.74 (3.44-6.54); and the c-index was 0.640. The HR for death for bilirubin 2 vs. 1 was 1.09 (0.82-1.44); bilirubin 3 vs. 1 was 2.37 (1.66-3.40); and the c-index was 0.533. Conclusions: ALBI outperforms CP in survival prognosis in Y90 treated patients. On sub-analyses, serum albumin (not bilirubin) appears to be the main driver of survival prediction. Our study supports the prognostic ability of ALBI and may suggest a role of albumin alone as a biomarker for patients with HCC.

14.
Transplantation ; 103(12): 2531-2538, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30951016

RESUMO

BACKGROUND: Despite lower socioeconomic status, Hispanics in the United States paradoxically maintain equal or higher average survival rates compared to non-Hispanic Whites (NHW). METHODS: We used multivariable Cox regression to assess whether this "Hispanic paradox" applies to patients with liver cirrhosis using a retrospective cohort of twenty 121 patients in a Chicago-wide electronic health record database. RESULTS: Our study population included 3279 (16%) Hispanics, 9150 (45%) NHW, 4432 (22%) African Americans, 529 (3%) Asians, and 2731 (14%) of other races/ethnic groups. Compared to Hispanics, NHW (hazard ratio [HR] 1.26; 95% confidence interval [CI], 1.16-1.37), African American (HR 1.26; 95% CI, 1.15-1.39), and other races/ethnic groups (HR 1.55; 95% CI, 1.40-1.71) had an increased risk of death despite adjustment for age, sex, insurance status, etiology of cirrhosis, and comorbidities. On stratified analyses, a mortality advantage for Hispanics compared to NHW was seen for alcohol cirrhosis (HR for NHW 1.35; 95% CI, 1.19-1.52), hepatitis B (HR for NHW 1.35; 95% CI, 0.98-1.87), hepatitis C (HR for NHW 1.21; 95% CI, 1.06-1.38), and nonalcoholic steatohepatitis (HR for NHW 1.14; 95% CI, 0.94-1.39). There was no advantage associated with Hispanic race over NHW in cases of hepatocellular carcinoma or cholestatic liver disease. CONCLUSIONS: Hispanic patients with cirrhosis experience a survival advantage over many other racial groups despite adjustment for multiple covariates.


Assuntos
Hispânico ou Latino/estatística & dados numéricos , Cirrose Hepática/etnologia , Vigilância da População , Sistema de Registros , Medição de Risco/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Socioeconômicos , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
15.
Cardiovasc Intervent Radiol ; 42(5): 700-711, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30824946

RESUMO

AIMS: To investigate laboratory parameters as predictors of overall survival (OS) for hepatocellular carcinoma (HCC) treated with radioembolization and develop/validate a scoring system. METHODS: With IRB approval, we included all patients with baseline alpha-fetoprotein (AFP) > 100 ng/dL from our prospectively acquired HCC radioembolization database. Neutrophil-lymphocyte ratio, albumin-bilirubin (ALBI), and AFP were measured at baseline and at 1-, 3-, and 6-month post-radioembolization Landmarks. OS was assessed from these Landmarks. Univariate/multivariate analyses were performed to evaluate OS predictability of these parameters. Baseline Imaging, Laboratory, and Combination scoring systems were developed. Developing/validating groups were created to investigate/validate the score's OS predictability. Time-dependent receiver operating characteristics (ROC) were evaluated. Patients were stratified into groups I, II, and III by using 25th and 75th percentile cutoffs according to change in Laboratory Score from baseline. RESULTS: 345/401 (86%), 238/401 (59%), and 167/401 (42%) patients had laboratory parameters available at the 1-, 3-, and 6-month Landmarks, respectively. ALBI and AFP were significant OS prognosticators at all Landmarks. The Laboratory Score [ALBI + (0.3 × LnAFP)] was developed/internally validated to predict OS from these Landmarks. Areas under the curve of time-dependent ROCs of the Baseline Imaging vs. Laboratory scores in predicting patient OS post 3 and 6 months Landmarks were 0.56 versus 0.82 and 0.57 versus 0.77, respectively. OS differences in groups I, II, and III according to change in Laboratory Score from baseline were significant (p < 0.001). CONCLUSIONS: Post-radioembolization AFP and ALBI scores were significant OS prognosticators. A decrease in post-therapeutic Laboratory Score, which combines AFP and ALBI, correlates with an improved OS.


Assuntos
Braquiterapia/métodos , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/radioterapia , alfa-Fetoproteínas/metabolismo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Curva ROC , Reprodutibilidade dos Testes , Análise de Sobrevida
16.
Am J Transplant ; 19(1): 98-109, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29985559

RESUMO

Noninvasive biomarkers are needed to monitor stable patients after kidney transplant (KT), because subclinical acute rejection (subAR), currently detectable only with surveillance biopsies, can lead to chronic rejection and graft loss. We conducted a multicenter study to develop a blood-based molecular biomarker for subAR using peripheral blood paired with surveillance biopsies and strict clinical phenotyping algorithms for discovery and validation. At a predefined threshold, 72% to 75% of KT recipients achieved a negative biomarker test correlating with the absence of subAR (negative predictive value: 78%-88%), while a positive test was obtained in 25% to 28% correlating with the presence of subAR (positive predictive value: 47%-61%). The clinical phenotype and biomarker independently and statistically correlated with a composite clinical endpoint (renal function, biopsy-proved acute rejection, ≥grade 2 interstitial fibrosis, and tubular atrophy), as well as with de novo donor-specific antibodies. We also found that <50% showed histologic improvement of subAR on follow-up biopsies despite treatment and that the biomarker could predict this outcome. Our data suggest that a blood-based biomarker that reduces the need for the indiscriminate use of invasive surveillance biopsies and that correlates with transplant outcomes could be used to monitor KT recipients with stable renal function, including after treatment for subAR, potentially improving KT outcomes.


Assuntos
Biomarcadores/sangue , Rejeição de Enxerto/diagnóstico , Transplante de Rim , Adulto , Idoso , Algoritmos , Biópsia , Feminino , Fibrose/diagnóstico , Taxa de Filtração Glomerular , Rejeição de Enxerto/sangue , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Resultado do Tratamento , Adulto Jovem
17.
J Vasc Interv Radiol ; 29(11): 1502-1510.e1, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30268638

RESUMO

PURPOSE: To longitudinally study clinical and radiologic outcomes of patients with hepatocellular carcinoma (HCC) who underwent yttrium-90 transarterial radioembolization (TARE) as a bridge to surgical resection. MATERIALS AND METHODS: TARE was performed in 31 patients with HCC before resection. Of patients, 25 underwent major hepatic resection (16 received right hepatectomy and 9 received trisegmentectomy), and 6 underwent partial hepatectomy. Clinical outcomes after TARE and after resection were recorded. Future liver remnant (FLR) was calculated before and after TARE, and actual liver remnant volume was calculated after resection. Radiologic response after TARE and pathologic necrosis were assessed. Overall and recurrence-free survivals after resection were estimated. RESULTS: Median time between TARE and resection was 2.9 months (interquartile range [IQR]: 2-5 months). Median FLR hypertrophy after TARE (and before resection) was 23.3% (IQR:10%-48%) for patients who had radiation lobectomy and 9% (IQR: 6%-25%) for patients who had radiation segmentectomy (P = .037). Median augmented hypertrophy of the liver remnant 3 months after resection was 72% (IQR:45%-88%) in patients who had radiation lobectomy and 94% (IQR: 72%-146%) in patients who had radiation segmentectomy. Complete, 50%-99%, and < 50% pathologic tumor necrosis was identified in 14 (45%), 10 (32%), and 7 (23%) tumors. Disease control was achieved in all 31 patients. Survival rates at 1 and 3 years were 96% and 86%, respectively. Median recurrence-free survival was 34.2 months (95% confidence interval,18.7-34.2). CONCLUSIONS: TARE can serve as a safe bridge to resection providing FLR hypertrophy and disease control.


Assuntos
Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/cirurgia , Embolização Terapêutica/métodos , Hepatectomia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirurgia , Compostos Radiofarmacêuticos/administração & dosagem , Radioisótopos de Ítrio/administração & dosagem , Adulto , Idoso , Biópsia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/secundário , Embolização Terapêutica/efeitos adversos , Feminino , Hepatectomia/efeitos adversos , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Regeneração Hepática , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Necrose , Recidiva Local de Neoplasia , Intervalo Livre de Progressão , Compostos Radiofarmacêuticos/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Radioisótopos de Ítrio/efeitos adversos
18.
Radiology ; 287(3): 1050-1058, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29688155

RESUMO

Purpose To report long-term outcomes of radiation segmentectomy (RS) for early hepatocellular carcinoma (HCC). The authors hypothesized that outcomes are comparable to curative treatments for patients with solitary HCC less than or equal to 5 cm and preserved liver function. Materials and Methods This retrospective study included 70 patients (median age, 71 years; range, 22-96 years) with solitary HCC less than or equal to 5 cm not amenable to percutaneous ablation who underwent RS (dose of >190 Gy) between 2003 and 2016. Patients who underwent subsequent curative liver transplantation were excluded to eliminate this confounding variable affecting survival. Radiologic response of time to progression and median overall survival were estimated by using the Kaplan-Meier method per the guidelines of the European Association for the Study of the Liver (EASL) and the World Health Organization (WHO). Results Seventy patients were treated with RS over 14 years. Sixty-three patients (90%) showed response by using EASL criteria, of which 41 (59%) showed complete response. Fifty patients (71%) achieved response by using WHO criteria, of which 11 (16%) achieved complete response. Response rates at 6 months were 86% and 49% by using EASL and WHO criteria, respectively. Median time to progression was 2.4 years (95% confidence interval: 2.1, 5.7), with 72% of patients having no target lesion progression at 5 years. Median overall survival was 6.7 years (95% confidence interval: 3.1, 6.7); survival probability at 1, 3, and 5 years was 98%, 66%, and 57%, respectively. Overall survival probability at 1, 3, and 5 years was 100%, 82%, and 75%, respectively, in patients with baseline tumor size less than or equal to 3 cm (n = 45) and was significantly longer than in patients with tumors greater than 3 cm (P = .026). Conclusion RS provides response rates, tumor control, and survival outcomes comparable to curative-intent treatments for selected patients with early-stage HCC who have preserved liver function. © RSNA, 2018 Online supplemental material is available for this article.


Assuntos
Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Progressão da Doença , Feminino , Humanos , Aumento da Imagem/métodos , Fígado/diagnóstico por imagem , Fígado/efeitos da radiação , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
20.
Hum Immunol ; 79(5): 277-282, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29408689

RESUMO

Kidney transplant recipients given donor hematopoietic stem cells from their HLA-identical living related donors have now been followed between 5 and 9½ years post-operatively. Recipients who were designated as tolerant (Tol) have remained so since the last report when the 5 year (biopsy associated) milestone was reached. There has been 1 mortality of a Tol patient, unrelated to the study protocol, while 5 (of 15) have remained Tol between 7 and 8½ years post-operatively. There has been continuing elevated T-regulatory (CD4+CD25HighCD127-FOXP3+) cells in PBMC previously reported on. Ten year renal transplant biopsies are tentatively planned.


Assuntos
Antígenos HLA/genética , Antígenos HLA/imunologia , Transplante de Células-Tronco Hematopoéticas , Transplante de Rim , Tolerância ao Transplante/imunologia , Adulto , Idoso , Protocolos Clínicos , Feminino , Seguimentos , Perfilação da Expressão Gênica , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/imunologia , Quimeras de Transplante/sangue , Quimeras de Transplante/imunologia
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