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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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Vacinas contra Hepatite B , Hepatite C , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Vacinas contra Hepatite B/efeitos adversos , Anticorpos Anti-Hepatite B , Vacinação , RNARESUMO
INTRODUCTION AND OBJECTIVES: Universal vaccination at birth and in infancy is key to the elimination of chronic hepatitis B infection. We aimed to assess hepatitis B immune-prophylaxis and perinatal transmission knowledge, in a large and ethnically diverse cohort of previously pregnant North American women, chronically infected with hepatitis B. MATERIALS AND METHODS: The Hepatitis B Research Network (HBRN) is comprised of 28 Clinical Centers in the United States and Canada. Female cohort participants were administered a questionnaire to assess: (1) their assertion of knowledge regarding HBV prophylaxis at birth, testing, and diagnosis of hepatitis B in their children, and (2) the percentage of affirmative to negative responses for each of the HBV-related interventions her child may have received. The relationship between asserted knowledge, actions taken and maternal demographics were assessed. RESULTS: A total of 351 mothers with 627 children born in or after 1992 were included. Median age at enrollment was 39.8 years. Mothers were mostly foreign-born with the largest percentage from Asia (73.4%) and Africa (11.7%). Of the 627 children, 94.5% had mothers who asserted that they knew whether their child had received HBIG or HBV vaccine at birth, for 88.8% of the children, their mothers indicated that they knew if their child was tested for HBV and for 84.5% of children, their mothers knew if the child was diagnosed with HBV infection. Among children whose mothers asserted knowledge of their HBV management, 95.3% were reported to have received HBIG or HBV vaccine, 83.4% of children were said to have been tested for HBV, and 4.8% of children were said to have been diagnosed with HBV. Younger maternal age was the only factor significantly associated with higher percentage of children for whom mothers reported knowledge of testing (p=0.02) or diagnosis of HBV (p=0.02). CONCLUSIONS: While high percentages of North American children had mothers asserting knowledge of HBV prophylaxis and testing, knowledge gaps remain, with mothers of 5.5-15.5% of children lacking knowledge of key components of the HBV prevention and diagnosis in the perinatal setting. Targeted education of HBsAg-positive mothers may aid in closing this gap and reducing vertical transmission.
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Conhecimentos, Atitudes e Prática em Saúde , Hepatite B Crônica/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez , Adulto , Canadá , Feminino , Anticorpos Anti-Hepatite B/uso terapêutico , Vacinas contra Hepatite B/uso terapêutico , Hepatite B Crônica/prevenção & controle , Humanos , Imunização Passiva , Fatores Imunológicos/uso terapêutico , Gravidez , Estados UnidosRESUMO
INTRODUCTION AND OBJECTIVES: The prevalence of alcohol, tobacco, and coffee use and association with liver health among North Americans with Chronic Hepatitis B (CHB) infection has not been well described. MATERIALS AND METHODS: The Hepatitis B Research Network includes an observational study of untreated CHB adults enrolled at 21 sites in the United States and Canada. Alcohol use was categorized as none, moderate, and at-risk based on the definition from the National Institute on Alcohol Abuse and Alcoholism; tobacco use as never, current and former; coffee use as none, 1-2 cups/day, and ≥3 cups/day. Linear regression and linear mixed models were used to associate lifestyle behaviors with ALT and FIB-4 values. RESULTS: 1330 participants met eligibility: 53% males, 71% Asian and the median age was 42 years (IQR: 34-52). Median ALT was 33U/L (IQR: 22-50), 37% had HBV DNA <103IU/mL, 71% were HBeAg negative, and 65% had a FIB-4 <1.45. At baseline, 8% of participants were at-risk alcohol drinkers, 11% were current smokers and 92% drank <3 cups of coffee/day. Current tobacco and 'at-risk' alcohol use, were significantly associated with elevated ALT levels in univariable analyses, however, these associations were not statistically significant when controlling for sociodemographic and HBV characteristics. CONCLUSIONS: In this large diverse cohort of untreated CHB participants, at-risk alcohol use, current tobacco use and limited coffee consumption did not have an association with high ALT and FIB-4 values. In contrast, significant associations were found between the frequency of these lifestyle behaviors and sociodemographic factors.
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Consumo de Bebidas Alcoólicas/epidemiologia , Café , Hepatite B Crônica/epidemiologia , Cirrose Hepática/epidemiologia , Fumar Tabaco/epidemiologia , Adolescente , Adulto , África/etnologia , Idoso , Alanina Transaminase/sangue , Ásia/etnologia , Povo Asiático , População Negra , Canadá/epidemiologia , DNA Viral/sangue , Feminino , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Humanos , Cirrose Hepática/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Índice de Gravidade de Doença , Estados Unidos/epidemiologia , População Branca , Adulto JovemRESUMO
BACKGROUND AND AIMS: Eleven million unauthorized immigrants reside in the United States and may account for 3% of deceased organ donors. Recently introduced federal and state legislation propose to address access to organ transplantation among unauthorized immigrants. The national landscape of liver transplantation (LT) for unauthorized immigrants is unknown. APPROACH AND RESULTS: We included all US LT recipients between March 2012 and December 2018 who were linked to Pew Center of Research data to estimate the population of unauthorized immigrants in each US state and by country of origin, based on US Census data. We categorized patients as unauthorized immigrants versus US citizens/residents. The main outcome measures were (1) the proportion of LTs performed for unauthorized immigrants compared with the proportion of unauthorized immigrants among total population in each US state and (2) graft failure and death post-LT. Of 43,192 LT recipients, 43,026 (99.6%) were US citizens/residents and 166 (0.4%) were unauthorized immigrants. Among unauthorized immigrants, most LTs were performed in California (47%) and New York (18%). The absolute difference in proportion of LTs performed for unauthorized immigrants compared with the proportion of unauthorized immigrants among the total population differed among states, ranging from +20% in California to -12% in Texas. The most common countries of birth among LT recipients who were unauthorized immigrants were Mexico (52%), Guatemala (7%), China (6%), El Salvador (5%), and India (5%). In competing risk analysis, unauthorized immigration status (vs. US citizens/residents) was associated with a similar risk of graft failure (subdistribution hazard ratio [sHR] 0.74; 95% confidence interval [CI], 0.40-1.34; P = 0.38) and death (sHR 0.68; 95% CI, 0.36-1.29; P = 0.23). CONCLUSIONS: LT for unauthorized immigrants is rare, and disparities in access to LT by state are present. Patient and graft survival among unauthorized immigrants is comparable with citizens/residents.
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Imigrantes Indocumentados/estatística & dados numéricos , China/etnologia , El Salvador/etnologia , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Guatemala/etnologia , Humanos , Índia/etnologia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Estados UnidosRESUMO
The development of multiple highly effective and safe direct-acting antivirals to treat hepatitis C virus (HCV) has resulted in greater ease and confidence in managing HCV infection in transplant recipients that in turn has impacted the solid organ transplant community as well. In the United States, the opioid epidemic has increased the number of overdose deaths with a concomitant increase in younger HCV viremic donors after brain death being identified. At the same time, a decrease in HCV viremic transplant candidates has led to a growing interest in exploring the use of HCV viremic liver and kidney donor allografts in HCV-negative recipients. To date, experience with the use of HCV viremic liver and kidney allografts in HCV-negative recipients is limited to a few small prospective research trials, case series, and case reports. There are also limited data on recipient and donor selection for HCV viremic liver and kidney allografts. In response to this rapidly changing landscape in the United States, experts in the field of viral hepatitis and liver and kidney transplantation convened a meeting to review current data on liver and kidney recipient selection and developed consensus opinions related specifically to recipient and donor selection of HCV viremic liver and kidney allografts.
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Antivirais/uso terapêutico , Hepatite C Crônica/transmissão , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Seleção de Pacientes , Complicações Pós-Operatórias/prevenção & controle , Aloenxertos/patologia , Aloenxertos/virologia , Antibioticoprofilaxia/normas , Biópsia , Consenso , Conferências de Consenso como Assunto , Seleção do Doador/normas , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Humanos , Rim/virologia , Transplante de Rim/normas , Fígado/patologia , Fígado/virologia , Transplante de Fígado/normas , Complicações Pós-Operatórias/virologia , Transplantados , Estados Unidos , Viremia/transmissão , Viremia/virologiaRESUMO
BACKGROUND: Prospective and longitudinal studies have examined liver donors' medical outcomes beyond the first 1 to 2 years postdonation. There is no analogous longitudinal evidence on long-term psychosocial outcomes, including patient-reported clinically significant mental health problems and perceptions of physical well-being. We examined prevalence, descriptive characteristics, and predictors of diagnosable mental health conditions and self-reported physical health problems, including fatigue and pain, in the long-term years after liver donation. METHODS: Donors from 9 centers who initially completed telephone interviews at 3 to 10 years postdonation (mean, 5.8 years; SD, 1.9) were reinterviewed annually for 2 years using validated measures. Outcomes were examined descriptively. Repeated-measures regression analyses evaluated potential predictors and correlates of outcomes. RESULTS: Of 517 donors initially interviewed (66% of those eligible), 424 (82%) were reassessed at least once. Prevalence rates of major depression and clinically significant pain were similar to general population norms; average fatigue levels were better than norms. All prevalence rates showed little temporal change. Anxiety and alcohol use disorder rates exceeded normative rates at 1 or more assessments. Longer postdonation hospitalization, female sex, higher body mass index, concerns about donation-related health effects, and burdensome donation-related financial costs were associated with increased risk for most outcomes (P's < 0.05). Men were at higher risk for alcohol use disorder (P < 0.001). CONCLUSIONS: Anxiety and alcohol use disorders were more common than would be expected; they may warrant increased research attention and clinical surveillance. Surveillance for long-term problems in the areas assessed may be optimized by targeting donors at higher risk based on identified predictors and correlates.
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Transplante de Fígado , Doadores Vivos , Saúde Mental , Adulto , Alcoolismo/epidemiologia , Ansiedade/epidemiologia , Estudos de Coortes , Depressão/epidemiologia , Fadiga/epidemiologia , Feminino , Humanos , Doadores Vivos/psicologia , Masculino , Dor/epidemiologia , Prevalência , Qualidade de Vida , Resultado do TratamentoRESUMO
INTRODUCTION: Recurrence of HCV infection in patients with chronic hepatitis C virus (HCV) at the time of liver transplantation is nearly universal and reduces the likelihood of graft and patient survival. MATERIALS AND METHODS: We evaluated outcomes of 17 patients (16 with HCV genotype 1 and 1 with genotype 4) who received up to 12 or 24 weeks of ledipasvir/sofosbuvir plus ribavirin prior to or up to the time of liver transplant in the SOLAR-1 and SOLAR-2 trials. In all patients, HCV RNA was < 15 IU/mL prior to transplant. At screening, 6 patients were Child-Pugh-Turcotte (CPT) class B and 11 were CPT class C. Seven patients underwent transplant prior to completing assigned treatment, with 4 treated for < 12 weeks. The primary endpoint was posttransplant virologic response 12 weeks after transplant (pTVR12) in patients with HCV RNA < 15 IU/mL at their last measurement prior to transplant. RESULTS: Overall, 94% (16/17) achieved pTVR12. All who achieved pTVR12 received at least 11 weeks of treatment. The single patient who did not achieve pTVR12 discontinued study drug on day 21 and underwent liver transplant the following day. The patient had HCV RNA < 15 IU/mL at post-transplant week 2 but died 15 days post-transplant because of multi-organ failure and septic shock. CONCLUSION: Among a small population of HCV patients with decompensated cirrhosis, virologic response to ledipasvir / sofosbuvir plus ribavirin prior to liver transplantation was maintained after transplantation, even if treatment was stopped early. Administration of ledipasvir / sofosbuvir plus ribavirin before liver transplant can prevent post-transplant HCV recurrence.
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Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Cirrose Hepática/cirurgia , Transplante de Fígado , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Resposta Viral Sustentada , Idoso , Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Quimioterapia Combinada , Feminino , Fluorenos/efeitos adversos , Genótipo , Hepacivirus/genética , Hepatite C/diagnóstico , Hepatite C/mortalidade , Hepatite C/virologia , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Cirrose Hepática/virologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Ribavirina/efeitos adversos , Sofosbuvir/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Carga ViralRESUMO
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/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Recidiva Local de Neoplasia/epidemiologia , alfa-Fetoproteínas/metabolismo , Idoso , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Prognóstico , Estudos Retrospectivos , Fatores Sexuais , Doadores de Tecidos , Carga TumoralRESUMO
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 Apoio para a Decisão , Seleção do Doador , Doença Hepática Terminal/cirurgia , Sobrevivência de Enxerto , Hepatite C/complicações , Transplante de Fígado/métodos , Doadores de Tecidos , Adulto , Fatores Etários , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/virologia , Feminino , Hepatite C/diagnóstico , Hepatite C/mortalidade , Humanos , Funções Verossimilhança , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: In nontransplant patients with chronic hepatitis C virus (HCV), HCV genotype has been linked with a differential response to antiviral therapy, risk of steatosis and fibrosis, as well as all-cause mortality, but the role of HCV genotypes in posttransplant disease progression is less clear. METHODS: Using the multicenter CRUSH-C cohort, genotype-specific rates of advanced fibrosis, HCV-specific graft loss and response of antiviral therapy were examined. RESULTS: Among 745 recipients (605 [81%] genotype 1, 53 [7%] genotype 2, and 87 [12%] genotype 3), followed for a median of 3.1 years (range, 2.0-8.0), the unadjusted cumulative rate of advanced fibrosis at 3 years was 31%, 19%, and 19% for genotypes 1, 2, and 3 (P = 0.008). After multivariable adjustment, genotype remained a significant predictor, with genotype 2 having a 66% lower risk (P = 0.02) and genotype 3 having a 41% lower risk (P = 0.07) of advanced fibrosis compared to genotype 1 patients. The cumulative 5-year rates of HCV-specific graft survival were 84%, 90%, and 94% for genotypes 1, 2, and 3 (P = 0.10). A total of 37% received antiviral therapy, with higher rates of sustained virologic response in patients with genotype 2 (hazard ratios, 5.10; P = 0.003) and genotype 3 (hazard ratios, 3.27; P = 0.006) compared to patients with genotype 1. CONCLUSION: Risk of advanced fibrosis and response to therapy are strongly influenced by genotype. Liver transplantation recipients with HCV genotype 1 have the highest risk of advanced fibrosis and lowest sustained virologic response rate. These findings highlight the need for genotype-specific management strategies.