RESUMEN
INTRODUCTION AND OBJECTIVES: Some studies suggest chronic HCV infection diminishes responses to the anti-HBV vaccine. We evaluated the efficacy of double versus standard dose HBV vaccination among HCV patients without cirrhosis. PATIENTS AND METHODS: 141 adults with untreated chronic HCV were randomized to HBV vaccination with double dose (40µg) or standard dose (20µg) at 0, 1 and 6 months; 70 healthy HCV-negative patients given standard dose served as controls. Vaccine response was defined by anti-HBs ≥10 mIU/mL. RESULTS: 128 patients (60 double, 68 standard doses) completed the study. Patients were of median age 52 years, 61% female, 60% fibrosis <2 of 4, and 76% genotype 1 with median 6-log 10 IU/mL HCV RNA. Overall seroprotection rate was 76.7% (95% CI: 65-87) in the 40µg versus 73.5% (95% CI: 63-84) in the 20µg dose HCV-positive groups (p =0.68) and 91.2% (95%CI:84-99) in HCV-negative controls (p =0.011 and 0.003, respectively). In multivariate logistic regression, vaccine dose (double vs. standard dose) was not associated with vaccine response (OR=0.63, p =0.33). Of 32 HCV-infected patients who were non-responders to 3- doses, 25 received the fourth dose of vaccine. The fourth dose seroconversion rate for the 40µg and 20µg groups were 45.5% and 21.4%, respectively. CONCLUSIONS: In HCV-infected patients without cirrhosis, impaired responses to HBV vaccination cannot be overcome by the use of double dose HBV vaccination, but adding a fourth dose of vaccine for non-responders may be an effective strategy. Other adjuvant measures are needed to enhance seroconversion rates in these patients. TRIAL REGISTER: U 1111-1264-2343 (www.ensaiosclinicos.gov.br).
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Vacunas contra Hepatitis B , Hepatitis C , Adulto , Humanos , Femenino , Persona de Mediana Edad , Masculino , Vacunas contra Hepatitis B/efectos adversos , Anticuerpos contra la Hepatitis B , Vacunación , ARNRESUMEN
UNLABELLED: Introduction. Men have higher risk for hepatocellular carcinoma (HCC) than women. Pre liver transplant (LT) alpha fetoprotein (AFP) levels strongly predict post LT HCC recurrence. Though women with HCC have higher AFP, the contribution of AFP level by gender to post LT HCC recurrence is unknown. MATERIAL AND METHODS: In this UNOSbased, retrospective cohort study we investigate sex differences in HCC recurrence among LT recipients with MELD exception between 2006-2010. Covariates include race, disease etiology, co-morbidities, AFP at listing and LT, tumor burden, loco-regional therapy, and donor risk index. HCC recurrence was assessed by competing risks regression. RESULTS: Of the eligible cohort (n = 5,002) included 3,872 men and 1,130 women. HCC recurred in 258 men (7%) and 66 women (6%). Median listing AFP was higher in women than men (14 vs. 11 ng/dL, p < 0.001). While no sex difference in overall HCC recurrence was detected (HR 0.9, 95% CI 0.7-1.2, p = 0.38), there was a strong interaction between gender and AFP on recurrence risk (p = 0.02). HCC recurrence was nearly three times higher in women (HR 4.2, 95% CI 2.2-8.2, p < 0.001) than men (HR 1.5, 95% CI 1.1-2.1, p = 0.02) with AFP at LT between 101-500 ng/dL. CONCLUSION: This study reveals novel sex differences in post LT HCC recurrence, which was nearly three times higher in women than men with high AFP at LT. Pre-LT AFP levels appear to carry a different prognosis in women than men, and a subset of female LT recipients may benefit from more intensive HCC surveillance after LT.
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Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Recurrencia Local de Neoplasia/epidemiología , alfa-Fetoproteínas/metabolismo , Anciano , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Estudios de Cohortes , Femenino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Pronóstico , Estudios Retrospectivos , Factores Sexuales , Donantes de Tejidos , Carga TumoralRESUMEN
Donor age has become the dominant donor factor used to predict graft failure (GF) after liver transplantation (LT) in hepatitis C virus (HCV) recipients. The purpose of this study was to develop and validate a model of corrected donor age (CDA) for HCV LT recipients that transforms the risk of other donor factors into the scale of donor age. We analyzed all first LT recipients with HCV in the United Network for Organ Sharing (UNOS) registry from January 1998 to December 2007 (development cohort, n = 14,538) and January 2008 to December 2011 (validation cohort, n = 7502) using Cox regression, excluding early GF (<90 days from LT). Accuracy in predicting 1 year GF (death or repeat LT) was assessed with the net reclassification index (NRI). In the development cohort, after controlling for pre-LT recipient factors and geotemporal trends (UNOS region, LT year), the following donor factors were independent predictors of GF, all P < 0.05: donor age (hazard ratio [HR], 1.02/year), donation after cardiac death (DCD; HR, 1.31), diabetes (HR, 1.23), height < 160 cm (HR, 1.13), aspartate aminotransferase (AST) ≥ 120 U/L (HR, 1.10), female (HR, 0.94), cold ischemia time (CIT; HR, 1.02/hour), and non-African American (non-AA) donor-African American (AA) recipient (HR, 1.65). Transforming these risk factors into the donor age scale yielded the following: DCD = +16 years; diabetes = +12 years; height < 160 cm = +7 years; AST ≥ 120 U/L = +5 years; female = -4 years; and CIT = +1 year/hour > 8 hours and -1 year/hour < 8 hours. There was a large effect of donor-recipient race combinations: +29 years for non-AA donor and an AA recipient but only +5 years for an AA donor and an AA recipient, and -2 years for an AA donor and a non-AA recipient. In a validation cohort, CDA better classified risk of 1-year GF versus actual age (NRI, 4.9%; P = 0.009) and versus the donor risk index (9.0%, P < 0.001). The CDA, compared to actual donor age, provides an intuitive and superior estimation of graft quality for HCV-positive LT recipients because it incorporates additional factors that impact LT GF rates.
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Técnicas de Apoyo para la Decisión , Selección de Donante , Enfermedad Hepática en Estado Terminal/cirugía , Supervivencia de Injerto , Hepatitis C/complicaciones , Trasplante de Hígado/métodos , Donantes de Tejidos , Adulto , Factores de Edad , Enfermedad Hepática en Estado Terminal/diagnóstico , Enfermedad Hepática en Estado Terminal/mortalidad , Enfermedad Hepática en Estado Terminal/virología , Femenino , Hepatitis C/diagnóstico , Hepatitis C/mortalidad , Humanos , Funciones de Verosimilitud , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Estados UnidosRESUMEN
With increasing attention being paid to optimizing patient outcomes, it has been proposed that liver transplantation (LT) for individuals with elevated body mass index (BMI) values and high Model for End-Stage Liver Disease (MELD) scores may adversely affect post-LT outcomes. We investigated the impact of BMI on post-LT outcomes in the context of MELD at LT. Using United Network for Organ Sharing data, we identified all adult (≥ 18 years) primary LT recipients from March 1, 2002 to September 30, 2011. BMI categories included the following: underweight, normal, overweight, class I obese, class II obese, and class III obese (<18.5; 18.5-24.9; 25-29.9; 30-34.9; 35-39.9; ≥ 40 kg/m(2), respectively). One-year post-LT death and graft loss were modeled using Cox regression, including interactions between BMI and MELD. A total of 45,551 adult recipients were identified: 68% male; median (interquartile range [IQR]) age 55 years (IQR, 49-60 years); MELD, 19 (IQR, 13-26); and donor risk index, 1.39 (IQR, 1.12-1.69). Representations in the BMI categories were underweight (n = 863, 2%), normal (n = 13,262, 29%), overweight (n = 16,329, 36%), class I obese (n = 9639, 21%), class II obese (n = 4062, 9%), and class III obese (n = 1396, 3%). In adjusted analyses, elevated BMI was not associated with increased risk for death or graft loss. Among the underweight, there were significant interactions between BMI and MELD with respect to death (P = 0.02) and graft loss (P = 0.01), with significantly increased risks for death (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.38-2.09; P = 0.006) and graft loss (HR, 1.45; 95% CI, 1.21-1.74; P = 0.02) among those with low MELD (≤ 26), compared to normal BMI recipients with low MELD. In conclusion, overweight and obese LT recipients do not have increased risk of death or graft loss regardless of MELD. Underweight patients are at increased risk for poor outcomes post-LT, specifically underweight recipients with low MELD have increased risk for death and graft loss. Mechanisms underlying this phenomenon warrant further investigation.
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Índice de Masa Corporal , Técnicas de Apoyo para la Decisión , Supervivencia de Injerto , Trasplante de Hígado/efectos adversos , Obesidad/complicaciones , Delgadez/complicaciones , Bases de Datos Factuales , Femenino , Humanos , Estimación de Kaplan-Meier , Trasplante de Hígado/mortalidad , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Obesidad/diagnóstico , Obesidad/mortalidad , Obesidad/fisiopatología , Oportunidad Relativa , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Medición de Riesgo , Factores de Riesgo , Delgadez/diagnóstico , Delgadez/mortalidad , Delgadez/fisiopatología , Factores de Tiempo , Resultado del Tratamiento , Estados UnidosRESUMEN
Repeat liver transplantation (LT) is controversial because of inferior outcomes versus primary LT. A minimum 1-year expected post-re-LT survival of 50% has been proposed. We aimed to identify combinations of Model for End-Stage Liver Disease (MELD), donor risk index (DRI), and recipient characteristics achieving this graft survival threshold. We identified re-LT recipients listed in the United States from March 2002 to January 2010 with > 90 days between primary LT and listing for re-LT. Using Cox regression, we estimated the expected probability of 1-year graft survival and identified combinations of MELD, DRI, and recipient characteristics attaining >50% expected 1-year graft survival. Re-LT recipients (n = 1418) had a median MELD of 26 and median age of 52 years. Expected 1-year graft survival exceeded 50% regardless of MELD or DRI in Caucasian recipients who were not infected with hepatitis C virus (HCV) of all ages and Caucasian HCV-infected recipients <50 years old. As age increased in HCV-infected Caucasian and non-HCV-infected African American recipients, lower MELD scores or lower DRI grafts were needed to attain the graft survival threshold. As MELD scores increased in HCV-infected African American recipients, lower-DRI livers were required to achieve the graft survival threshold. Use of high-DRI livers (>1.44) in HCV-infected recipients with a MELD score > 26 at re-LT failed to achieve the graft survival threshold with recipient age ≥ 60 years (any race), as well as at age ≥ 50 years for Caucasians and at age < 50 years for African Americans. Strategic donor selection can achieve >50% expected 1-year graft survival even in high-risk re-LT recipients (HCV infected, older age, African American race, high MELD scores). Low-risk transplant recipients (age < 50 years, non-HCV-infected) can achieve the survival threshold with varying DRI and MELD scores.
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Selección de Donante/normas , Enfermedad Hepática en Estado Terminal/cirugía , Rechazo de Injerto/prevención & control , Trasplante de Hígado/normas , Donantes de Tejidos , Receptores de Trasplantes , Listas de Espera , Adulto , Femenino , Rechazo de Injerto/mortalidad , Supervivencia de Injerto , Humanos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Reoperación/normas , Factores de Riesgo , Tasa de Supervivencia/tendencias , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
Studies of cancer among farm workers are difficult to conduct and interpret given the unique nature of this occupational group. The transitory nature of the work, high levels of poverty, and lack of legal documentation make epidemiologic studies difficult to accomplish. Nevertheless, this workforce in the United States, which numbers as much as 3 million persons, is a high risk population due to exposures to numerous toxic substances, including excessive sunlight, heat, dangerous machinery, fumes, fertilizers, dust, and pesticides. We summarize characteristics of farm workers (i.e., demographics, health care) from the National Agricultural Workers Survey (NAWS) and the California Agricultural Workers Survey (CAWS) and present findings from a series of studies conducted among farm workers in California. The epidemiology literature was reviewed and methods for a unique farm worker union-based epidemiologic study are presented. Farm workers in California and the rest of the United States, many of whom are seasonal and migrant workers are at elevated risk for numerous forms of cancer compared to the general population and specific pesticides may be associated with this altered risk. Elevated risks have been found for lymphomas and prostate, brain, leukemia, cervix, and stomach cancers.