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2.
Artigo em Inglês | MEDLINE | ID: mdl-38774116

RESUMO

Background: Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) has been the gold standard for diagnosing coronavirus disease 2019 (COVID-19) but has a lag time for the results. An effective prediction algorithm for infectious COVID-19, utilized at the emergency department (ED), may reduce the risk of healthcare-associated COVID-19. Objective: To develop a prototypic prediction model for infectious COVID-19 at the time of presentation to the ED. Material and methods: Retrospective cohort study of all adult patients admitted to Singapore General Hospital (SGH) through ED between March 15, 2020, and December 31, 2022, with admission of COVID-19 RT-PCR results. Two prediction models were developed and evaluated using area under the curve (AUC) of receiver operating characteristics (ROC) to identify infectious COVID-19 patients (cycle threshold (Ct) of <25). Results: Total of 78,687 patients were admitted to SGH through ED during study period. 6,132 of them tested severe acute respiratory coronavirus 2 positive on RT-PCR. Nearly 70% (4,226 of 6,132) of the patients had infectious COVID-19 (Ct<25). Model that included demographics, clinical history, symptom and laboratory variables had AUROC of 0.85 with sensitivity and specificity of 80.0% & 72.1% respectively. When antigen rapid test results at ED were available and added to the model for a subset of the study population, AUROC reached 0.97 with sensitivity and specificity of 95.0% and 92.8% respectively. Both models maintained respective sensitivity and specificity results when applied to validation data. Conclusion: Clinical predictive models based on available information at ED can be utilized for identification of infectious COVID-19 patients and may enhance infection prevention efforts.

3.
J Med Virol ; 85(1): 26-33, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23023992

RESUMO

Entecavir switch is one of the treatment options for lamivudine-resistant hepatitis B (HBV) patients in Asia. This study examined the outcome of patients with different baseline resistance genotypes in a cohort study. In this study, 14 patients with chronic HBV were treated with entecavir 1 mg/day for 5 years. Enrolment criteria include: documented lamivudine resistant mutations, treatment with adefovir 10 mg/day for at least 24 weeks, and Child-Pugh score <7. Most had previous failed adefovir therapy and compensated cirrhosis of the liver. Clinical outcomes, liver biochemistries, and HBV DNA were monitored regularly. Patients with virologic breakthrough were rescued with add-on adefovir. At the end of the treatment period, the mean HBV DNA fell from 5.92 × 10(6) (baseline) to 3.67 × 10(1) IU/ml. The presence of a HBV polymerase rtM204V mutation at the baseline was found to be the major risk factor for adverse outcomes. Compared to the patients with the rtM204I mutant, patients with the rtM204V mutant had increased risk of virologic breakthrough (80% vs. 0%, P = 0.010) requiring add-on adefovir, slower virologic responses (log rank test, P = 0.0011), failure to reach undetectable HBV DNA levels (60% vs. 0%, P = 0.045), and higher risk of entecavir-resistance (60% vs. 0%, P = 0.045). All the patients with rtM204I and rtA181 mutants had undetectable HBV DNA from 18th month. In summary, lamivudine-resistant HBV patients with the rtM204V mutation have the highest risk of developing entecavir resistance, and entecavir monotherapy should be avoided. Those with the rtM204I and rtA181V mutations may have lower risks, but regular surveillance for viral breakthrough is required.


Assuntos
Antivirais/farmacologia , Farmacorresistência Viral , Guanina/análogos & derivados , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Lamivudina/farmacologia , Adulto , Ásia , Análise Química do Sangue , Estudos de Coortes , DNA Viral/sangue , Feminino , Genótipo , Guanina/farmacologia , Vírus da Hepatite B/classificação , Vírus da Hepatite B/isolamento & purificação , Humanos , Fígado/enzimologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Taxa de Mutação , Mutação de Sentido Incorreto , DNA Polimerase Dirigida por RNA/genética , Resultado do Tratamento , Carga Viral
4.
Liver Int ; 33(4): 642-6, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23346997

RESUMO

AIM: Few cases of primary entecavir resistance in chronic hepatitis B patients have been reported to date. The serial profiling of the HBV polymerase gene mutations from a treatment-naive patient who developed drug resistance after 32 months of entecavir therapy is presented here. DESIGN: Serum samples were collected at multiple time points from before the start of therapy to virological and biochemical breakthrough. The evolution of the hepatitis B virus polymerase gene mutations was analysed with commercial line probe assay and pyrosequencing. RESULTS: Drug resistance mutation analysis by pyrosequencing revealed a two-step process in the selection of drug resistance. The patient had a good initial response to entecavir 0.5 mg/day. A partially resistant HBV strain first emerged as the predominant species from as early as 2 weeks. After a period of non-compliance to therapy, there was virological breakthrough, which resolved on restarting entecavir. Shortly after, there was secondary failure of entecavir therapy, caused by a new resistant strain carrying all three mutations required. CONCLUSION: In this patient, pre-existence of minor population of partially resistant viral strains and treatment non-compliance probably contributed to his development of primary entecavir resistance.


Assuntos
Antivirais/uso terapêutico , Farmacorresistência Viral/genética , Produtos do Gene pol/genética , Guanina/análogos & derivados , Vírus da Hepatite B/genética , Hepatite B/tratamento farmacológico , Mutação , Biomarcadores/sangue , Análise Mutacional de DNA , DNA Viral/sangue , Genótipo , Guanina/uso terapêutico , Hepatite B/sangue , Hepatite B/diagnóstico , Vírus da Hepatite B/enzimologia , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de Tempo , Falha de Tratamento
5.
Infect Dis Health ; 28(2): 81-87, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37032572

RESUMO

BACKGROUND: Increased transmissibility of severe-acute-respiratory-syndrome-coronavirus-2(SARS-CoV-2) variants, such as the Omicron-variant, presents an infection-control challenge. We contrasted nosocomial transmission amongst hospitalized inpatients across successive pandemic waves attributed to the Delta- and Omicron variants, over a 9-month period in which enhanced-infection-prevention-measures were constantly maintained. METHODS: Enhanced-infection-prevention-measures in-place at a large tertiary hospital included universal N95-usage, routine-rostered-testing (RRT) for all inpatient/healthcare-workers (HCWs), rapid-antigen-testing (RAT) for visitors, and outbreak-investigation coupled with enhanced-surveillance (daily-testing) of exposed patients. The study-period lasted from 21st June 2021-21st March 2022. Chi-square test and multivariate-logistic-regression was utilized to identify factors associated with onward transmission and 28d-mortality amongst inpatient cases of hospital-onset COVID-19. RESULTS: During the Delta-wave, hospital-onset cases formed 2.7% (47/1727) of all COVID-19 cases requiring hospitalisation; in contrast, hospital onset-cases formed a greater proportion (17.7%, 265/1483; odds-ratio, OR = 7.78, 95%CI = 5.65-10.70) during the Omicron-wave, despite universal N95-usage and other enhanced infection-prevention measures that remained unchanged. The odds of 28d-mortality were higher during the Delta-wave compared to the Omicron-wave (27.7%, 13/47, vs. 10.6%, 28/265, adjusted-odds-ratio, aOR = 2.78, 95%CI = 1.02-7.69). Onward-transmission occurred in 21.2% (66/312) of hospital-onset cases; being on enhanced-surveillance (daily-testing) was independently associated with lower odds of onward-transmission (aOR = 0.18, 95%CI = 0.09-0.38). Costs amounted to $USD7141 per-hospital-onset COVID-19 case. CONCLUSION: A surge of hospital-onset COVID-19 cases was encountered during the Omicron-wave, despite continuation of enhanced infection-prevention measures; mortality amongst hospital-onset cases was reduced. The Omicron variant poses an infection-control challenge in contrast to Delta; surveillance is important especially in settings where infrastructural limitations make room-sharing unavoidable, despite the high risk of transmission.


Assuntos
COVID-19 , Infecção Hospitalar , Humanos , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Pandemias , Centros de Atenção Terciária
6.
Infect Control Hosp Epidemiol ; 44(1): 8-16, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35285435

RESUMO

OBJECTIVE: To describe OXA-48-like carbapenem-producing Enterobacteriaceae (CPE) outbreaks at Singapore General Hospital between 2018 and 2020 and to determine the risk associated with OXA-48 carriage in the 2020 outbreak. DESIGN: Outbreak report and case-control study. SETTING: Singapore General Hospital (SGH) is a tertiary-care academic medical center in Singapore with 1,750 beds. METHODS: Active surveillance for CPE is conducted for selected high-risk patient cohorts through molecular testing on rectal swabs or stool samples. Patients with CPE are isolated or placed in cohorts under contact precautions. During outbreak investigations, rectal swabs are repeated for culture. For the 2020 outbreak, a retrospective case-control study was conducted in which controls were inpatients who tested negative for OXA-48 and were selected at a 1:3 case-to-control ratio. RESULTS: Hospital wide, the median number of patients with healthcare-associated OXA-48 was 2 per month. In the 3-year period between 2018 and 2020, 3 OXA-48 outbreaks were investigated and managed, involving 4 patients with Klebsiella pneumoniae in 2018, 55 patients with K. pneumoniae or Escherichia coli in 2019, and 49 patients with multispecies Enterobacterales in 2020. During the 2020 outbreak, independent risk factors for OXA-48 carriage on multivariate analysis (49 patients and 147 controls) were diarrhea within the preceding 2 weeks (OR, 3.3; 95% CI, 1.1-10.7; P = .039), contact with an OXA-48-carrying patient (OR, 8.7; 95% CI, 1.9-39.3; P = .005), and exposure to carbapenems (OR, 17.2; 95% CI, 2.2-136; P = .007) or penicillin (OR, 16.6; 95% CI, 3.8-71.0; P < .001). CONCLUSIONS: Multispecies OXA-48 outbreaks in our institution are likely related to a favorable ecological condition and selective pressure exerted by antimicrobial use. The integration of molecular surveillance epidemiology of the healthcare environment is important in understanding the risk of healthcare-associated infection to patients.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Enterobacteriaceae , Humanos , beta-Lactamases/análise , Proteínas de Bactérias/análise , Estudos Retrospectivos , Estudos de Casos e Controles , Centros de Atenção Terciária , Singapura/epidemiologia , Enterobacteriaceae , Infecções por Enterobacteriaceae/epidemiologia , Surtos de Doenças , Klebsiella pneumoniae , Escherichia coli , Carbapenêmicos/uso terapêutico , Atenção à Saúde
7.
Infect Control Hosp Epidemiol ; 44(6): 1014-1018, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35473629

RESUMO

Sporadic clusters of healthcare-associated coronavirus disease 2019 (COVID-19) occurred despite intense rostered routine surveillance and a highly vaccinated healthcare worker (HCW) population, during a community surge of the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) B.1.617.2 δ (delta) variant. Genomic analysis facilitated timely cluster detection and uncovered additional linkages via HCWs moving between clinical areas and among HCWs sharing a common lunch area, enabling early intervention.


Assuntos
COVID-19 , Viroses , Humanos , SARS-CoV-2/genética , Hospitais
8.
Mol Cancer ; 11: 14, 2012 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-22439738

RESUMO

BACKGROUND: We had previously demonstrated overexpression of fibroblast growth factor receptor-4 (FGFR4) in hepatocellular carcinoma (HCC). However, additional molecular mechanisms resulting in amplified FGFR4 signaling in HCC remain under-studied. Here, we studied the mechanistic role of its co-receptor klotho-beta (KLB) in driving elevated FGFR4 activity in HCC progression. RESULTS: Quantitative real-time PCR analysis identified frequent elevation of KLB gene expression in HCC tumors relative to matched non-tumor tissue, with a more than two-fold increase correlating with development of multiple tumors in patients. KLB-silencing in Huh7 cells decreased cell proliferation and suppressed FGFR4 downstream signaling. While transient repression of KLB-FGFR4 signaling decreased protein expression of alpha-fetoprotein (AFP), a HCC diagnostic marker, prolonged inhibition enriched for resistant HCC cells exhibiting increased liver stemness. CONCLUSIONS: Elevated KLB expression in HCC tissues provides further credence to the oncogenic role of increased FGFR4 signaling in HCC progression and represents a novel biomarker to identify additional patients amenable to anti-FGFR4 therapy. The restricted tissue expression profile of KLB, together with the anti-proliferative effect observed with KLB-silencing, also qualifies it as a specific and potent therapeutic target for HCC patients. The enrichment of a liver stem cell-like population in response to extended KLB-FGFR4 repression necessitates further investigation to target the development of drug resistance.


Assuntos
Carcinoma Hepatocelular/metabolismo , Glucuronidase/metabolismo , Neoplasias Hepáticas/metabolismo , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células , Glucuronidase/genética , Células Hep G2 , Humanos , Immunoblotting , Proteínas Klotho , Neoplasias Hepáticas/genética , RNA Interferente Pequeno , Reação em Cadeia da Polimerase em Tempo Real , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/genética
9.
Gastrointest Endosc ; 76(4): 756-60, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22840293

RESUMO

BACKGROUND: There is no satisfactory treatment for nonalcoholic steatohepatitis (NASH). The Bioenterics intragastric balloon (BIB) can be an effective treatment for weight reduction in obese patients. OBJECTIVE: We evaluated the efficacy of the BIB in improving the histology of NASH in obese patients. DESIGN: Randomized, controlled study. SETTING: University hospital. PATIENTS: Obese patients with body mass indexes (BMI) ≥27 kg/m(2) and who had histologic evidence of NASH were recruited. INTERVENTION: Patients were randomly assigned to a step 1 American Heart Association (AHA) diet plus exercise and BIB placement or step 1 AHA diet plus exercise and sham BIB placement for a period of 6 months. MAIN OUTCOME MEASUREMENTS: Liver histology was the primary outcome measure recorded before and after treatment. RESULTS: A total of 18 patients completed the study. Baseline characteristics of the BIB and sham groups were similar. At 6 months, a significant reduction in the mean BMI was seen in the BIB group (1.52 vs 0.8; P = .0008). The median nonalcoholic fatty liver disease activity scores at the end of treatment were significantly lower in the BIB-treated compared with the sham-treated groups (2 [0.75] vs 4 [2.25]; P = .03). There was a trend toward improvement in the median steatosis scores (1 [0.75] vs 1 [1]; P = .075). There was no change in the median loblular inflammation, hepatocellular ballooning, or fibrosis scores in both groups after treatment. LIMITATIONS: Pilot study with small numbers and short duration. CONCLUSION: Results from this pilot study demonstrated that addition of BIB for 6 months provided a greater loss of BMI and improvement in 2 of 5 histologic parameters of nonalcoholic fatty liver disease. A longer study with larger numbers will be required to prove whether or not the therapy is meaningful in the treatment of NASH.


Assuntos
Endoscopia Gastrointestinal , Fígado Gorduroso/terapia , Balão Gástrico , Fígado/patologia , Obesidade/complicações , Adulto , Idoso , Índice de Massa Corporal , Terapia Combinada , Dietoterapia , Terapia por Exercício , Fígado Gorduroso/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Projetos Piloto , Estudos Prospectivos , Método Simples-Cego , Resultado do Tratamento , Redução de Peso
10.
Am J Infect Control ; 50(4): 465-468, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35108584

RESUMO

Sporadic clusters of health care-associated COVID-19 infection occurred in a highly vaccinated health care-workers and patient population, over a 3-month period during ongoing community transmission of the B.1.617.2 variant. Enhanced infection-prevention measures and robust surveillance systems, including routine-rostered-testing of all inpatients and staff and usage of N95-respirators in all clinical areas, were insufficient in achieving zero health care-associated transmission. The unvaccinated and immunocompromised remain at-risk and should be prioritized for enhanced surveillance.


Assuntos
COVID-19 , COVID-19/prevenção & controle , Atenção à Saúde , Surtos de Doenças , Humanos , Pacientes Internados , SARS-CoV-2
11.
Gastroenterology ; 139(2): 632-43, 643.e1-4, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20347819

RESUMO

BACKGROUND & AIMS: C/EBPalpha (cebpa) is a putative tumor suppressor. However, initial results indicated that cebpa was up-regulated in a subset of human hepatocellular carcinomas (HCCs). The regulation and function of C/EBPalpha was investigated in HCC cell lines to clarify its role in liver carcinogenesis. METHODS: The regulation of C/EBPalpha expression was studied by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, immunohistochemistry, methylation-specific PCR, and chromatin immunoprecipitation assays. C/EBPalpha expression was knocked-down by small interfering RNA or short hairpin RNA. Functional assays included colony formation, methylthiotetrazole, bromodeoxyuridine incorporation, and luciferase-reporter assays. RESULTS: Cebpa was up-regulated at least 2-fold in a subset (approximately 55%) of human HCCs compared with adjacent nontumor tissues. None of the up-regulated samples were positive for hepatitis C infection. The HCC cell lines Hep3B and Huh7 expressed high, PLC/PRF/5 intermediate, HepG2 and HCC-M low levels of C/EBPalpha, recapitulating the pattern of expression observed in HCCs. No mutations were detected in the CEBPA gene in HCCs and cell lines. C/EBPalpha was localized to the nucleus and functional in Hep3B and Huh7 cells; knocking-down its expression reduced target-gene expression, colony formation, and cell growth, associated with a decrease in cyclin A and CDK4 concentrations and E2F transcriptional activity. Epigenetic mechanisms including DNA methylation, and the binding of acetylated histone H3 to the CEBPA promoter-regulated cebpa expression in the HCC cells. CONCLUSIONS: C/EBPalpha is up-regulated in a subset of HCCs and has growth-promoting activities in HCC cells. Novel oncogenic mechanisms involving C/EBPalpha may be amenable to epigenetic regulation to improve treatment outcomes.


Assuntos
Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Carcinoma Hepatocelular/metabolismo , Proliferação de Células , Neoplasias Hepáticas/metabolismo , Western Blotting , Proteínas Estimuladoras de Ligação a CCAAT/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Núcleo Celular/metabolismo , Imunoprecipitação da Cromatina , Ciclina A/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Metilação de DNA , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Histonas/metabolismo , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima
12.
J Clin Gastroenterol ; 45(9): 818-23, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21921845

RESUMO

GOALS: To determine the clinical outcome of chronic hepatitis B cirrhotics on antiviral therapy. BACKGROUND: The long-term outcome of hepatitis B cirrhotics on therapy remains to be characterized. METHODS: A large clinic cohort of chronic hepatitis B cirrhotic patients were enrolled in a treatment program of lamivudine ± adefovir therapy. Patients were analyzed for clinical outcomes, and predictors of these outcomes were evaluated by multivariate analysis. Clinical outcomes of ascites, encephalopathy, hepatocellular carcinoma (HCC), and progression in Child-Pugh score, Model for End-stage Liver Disease score, and mortality were assessed. Data were analyzed by Kaplan-Meier graphs, log-rank test, and Cox regression. RESULTS: Of 143 chronic hepatitis B cirrhotics, 19.6% had decompensated cirrhosis. At 5 years, the mean survival was 83.6%, development of ascites, HCC, encephalopathy, and deterioration in Child-Pugh score were 7.0%, 15.9%, 10.8%, and 16.9%, respectively. The overall progression of liver-related complications was 32.8% at 5 years. Multivariate analysis showed that ascites, albumin ≤28 g/L, Child-Pugh score ≥7.9, Model for End-stage Liver Disease score ≥10.9 were significantly associated with liver-related complications. Low albumin and low hepatitis B virus DNA were independent factors for liver-associated mortality. Lamivudine resistance did not affect mortality or liver disease progression. When stratified by Child-Pugh status, the mean survival of those with Child C cirrhosis was worse than Child A and B cirrhosis (P<0.001, log-rank test). Early deaths (≤12 mo) were due to liver failure or sepsis, whereas deaths ≥12 mo were mainly due to HCC. CONCLUSION: Decompensated chronic hepatitis B cirrhotics may suffer early mortality despite antiviral treatment, and therefore should be considered for early liver transplantation.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Adenina/análogos & derivados , Adenina/uso terapêutico , Idoso , Estudos de Coortes , Progressão da Doença , Quimioterapia Combinada , Feminino , Seguimentos , Hepatite B Crônica/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Lamivudina/uso terapêutico , Cirrose Hepática/fisiopatologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Organofosfonatos/uso terapêutico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento
13.
Gastroenterology ; 137(2): 682-90, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19394336

RESUMO

BACKGROUND & AIMS: Tumor and viral antigens are expressed by hepatocellular carcinoma (HCC) in patients with chronic hepatitis B, but little is known about the immunodominance and function of tumor- and virus-specific CD8+ T cells in these patients. METHODS: HLA-A2-restricted T-cell responses to 16 tumor antigens and hepatitis B virus (HBV) proteins were tested using 49 previously described epitopes. Cells from 30 HLA-A2+, HBV-infected patients (10 with HCC, 10 with HBV cirrhosis, and 10 HBV but no cirrhosis) were analyzed, after expansion, by enzyme-linked immunosorbent spot (ELISPOT). Interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-2 production, as well as expression of the degranulation marker CD107a on tumor-specific CD8+ T cells, were evaluated. RESULTS: Cells from all groups had tumor-specific responses. The tumor antigens NY-ESO-1 and SSX-2 were most frequently targeted and were immunogenic in the HLA-A2 subtypes that are characteristic of Asian ethnicity. Tumor-specific T cells had low affinities; T cells from non-HCC patients were polyfunctional (IFN-gamma+, TNF-alpha+, CD107a+) and those from HCC patients displayed an exhausted phenotype (IFN-gamma+, CD107a+). Programmed Death 1 (PD-1) was expressed at higher levels on T cells from tumor and liver than peripheral blood from HCC patients and might contribute to T-cell exhaustion. Blocking PD-1/PD-L1 increased the frequency of tumor-specific T cells in HCC patients but did not restore T cell function. CONCLUSIONS: Patients with or without HCC have a quantitative and functional hierarchy of tumor-specific T cells. HLA-A2-restricted T cells from HCC patients target NY-ESO-1, but exist in an exhausted state that might require additional activation to restore function.


Assuntos
Antígenos de Neoplasias/metabolismo , Linfócitos T CD8-Positivos/imunologia , Carcinoma Hepatocelular/imunologia , Hepatite B Crônica/imunologia , Cirrose Hepática/imunologia , Neoplasias Hepáticas/imunologia , Adulto , Antígenos de Neoplasias/imunologia , Biomarcadores Tumorais/metabolismo , Linfócitos T CD8-Positivos/patologia , Carcinoma Hepatocelular/virologia , Epitopos/imunologia , Feminino , Antígeno HLA-A2/imunologia , Antígeno HLA-A2/metabolismo , Hepatite B Crônica/virologia , Humanos , Cirrose Hepática/virologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Probabilidade , Valores de Referência , Sensibilidade e Especificidade , Células Tumorais Cultivadas
14.
Hepatology ; 47(4): 1108-17, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18318043

RESUMO

UNLABELLED: The relationship between stages of chronic hepatitis B liver disease and health-related quality of life (HRQoL) is an important aspect of the overall management of hepatitis B virus (HBV) infection, yet is not well characterized. Consequently we sought to examine HRQoL in HBV patients, stratified by disease severity, compared with normal controls and hypertensive patients, using the Short Form 36 Health Survey (SF-36) and the EQ-5D self-report questionnaire. Univariate and multivariate analyses were then performed. A total of 432 HBV (156 asymptomatic carriers, 142 chronic hepatitis B, 66 compensated cirrhosis, 24 decompensated cirrhosis, 22 hepatocellular carcinoma, and 22 post-liver transplant) patients, 93 hypertensive patients, and 108 normal controls participated in the study. Multivariate analysis showed that normal controls and asymptomatic carriers had similar SF-36 scores, which were better than those for hypertensive patients, but with development of chronic hepatitis B and compensated cirrhosis, showed a significant decrease in general health and the mental dimension, whereas those with advanced liver disease (decompensated cirrhosis and hepatocellular carcinoma) had significantly lower scores in all components (P < 0.05), indicating that the physical component deteriorates only with advanced liver disease. Similar results were obtained with EQ5D. Post-liver transplant patients had similar HRQoL to patients with decompensated cirrhosis and hepatocellular carcinoma, although there was a trend toward improvement. CONCLUSION: Our results showed that HRQoL in asymptomatic carriers is comparable to those of normal controls and better than hypertensive patients, but deteriorates with disease progression, initially in general health and mental dimensions, but with advanced disease all dimensions are affected.


Assuntos
Hepatite B/fisiopatologia , Qualidade de Vida , Adulto , Análise de Variância , Estudos de Casos e Controles , Progressão da Doença , Feminino , Hepatite B/psicologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade
16.
J Gastroenterol Hepatol ; 23(4): 599-605, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17645483

RESUMO

BACKGROUND AND AIM: Primary biliary cirrhosis (PBC) is infrequent in Asians. Among Asian patients with PBC, information on natural course is scarce. The aim of this study was to study the clinical course and prognosticators among Asians with PBC. METHODS: During 1990-2005, patients diagnosed with PBC at the National University Hospital, Singapore, constituted the retrospective cohort. Their demographic characteristics were evaluated. To evaluate the prognostic factors and natural course, two outcome measures were assessed: hepatic decompensation and death or liver transplant. Multivariate analysis was undertaken to identify factors associated with hepatic decompensation and terminal event (death or liver transplantation). RESULTS: Thirty-four PBC patients aged 56.8 +/- 1.8 years (mean +/- SEM) of whom 32 (94%) were women were included. Thirty-two (94%) of them were of Chinese origin. At presentation, 18 (53%) were symptomatic in the form of jaundice (n = 9, 26.5%), pruritus (n = 6, 17.6%) and fatigue (n = 5, 14.7%). During 4.80 +/- 0.7 (range 0.02-15.03) years follow up, 6/16 (37.5%) asymptomatic patients developed symptoms. After 5 years, 17.6% (n = 6) and 8.8% (n = 3) had hepatic decompensation and terminal event, respectively. Sicca syndrome was present in 26% (n = 9) of patients. Multivariate analysis revealed that serum bilirubin level at presentation was the sole determinant of decompensation. Rate of change of laboratory indices did not predict either event. CONCLUSION: In Singapore, Chinese women constitute most of the PBC patients. Elevated serum bilirubin level at presentation was the sole predictive marker associated with dismal outcome.


Assuntos
Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Grupos Raciais , Estudos Retrospectivos , Singapura/epidemiologia
18.
Ann Acad Med Singap ; 36(10): 797-800, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17987228

RESUMO

INTRODUCTION: Hepatitis B virus (HBV) infection is endemic in Asia. Good public knowledge on disease transmission is one way of controlling spread of HBV. We aimed to study the general knowledge on HBV among the general public in Singapore, which is moderately prevalent with HBV. MATERIALS AND METHODS: Before conducting a public education seminar on liver diseases, a 16-point questionnaire survey was conducted among the participants. Misperceptions (if any) were identified, and factors associated with knowledge score were analysed by multivariate analysis. RESULTS: One hundred and ninety-two subjects completed the questionnaire. The mean age was 52 years, 78 (41%) were male, 183 (95%) were Chinese, 17 (9%) were known hepatitis B carriers and 73 (38%) had completed college education. The mean knowledge score was 10.7 (out of a maximum of 16). Most misperceptions were in the category of HBV transmission. At multivariate analysis, having college education was the only independent factor associated with a high knowledge score. CONCLUSION: Although HBV infection is moderately prevalent in Singapore, many misperceptions existed among the general public, especially on the mode of transmission. Better education was related to better knowledge of HBV. Further public education should be targeted to clear the misperceptions identified, and be specifically targeted to the less educated.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Hepatite B/transmissão , Feminino , Educação em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Singapura , Inquéritos e Questionários
20.
Hepatol Int ; 7(2): 451-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26201777

RESUMO

PURPOSE: Practice guidelines for chronic hepatitis B (CHB) assist physicians in management; however, there are also areas where they provide no guidance. This paper aimed to examine treatment preferences for CHB among physicians based upon the Asia Pacific Association for the Study of the Liver (APASL) consensus guidelines 2008. METHODS: A questionnaire was prepared consisting of 18 questions grouped into 8 sections: basic information of participants, the proportion and number of CHB patients on treatment, case scenarios of treatment initiation, preferences for antiviral therapy, scenarios for stopping and continuing antiviral therapy, monitoring patients during therapy, and viral resistance management. The questionnaire was introduced to the APASL 2009 conference delegates. RESULTS: A total of 508 participants from 34 countries participated in the survey. Lamivudine or peg-interferon monotherapy was the preferred first-line therapy, while lamivudine/adefovir combination was the drug of choice for rescue therapy. Drug efficacy and cost were the most important factors to consider before initiating treatment, while viral resistance had a low priority. In general, the APASL guideline was strictly followed in about 50-60 % of the scenarios (initiating, stopping, or continuing antiviral therapy). CONCLUSIONS: The survey concluded that clinical management preferences differed from APASL guidelines in many instances.

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