RESUMO
Predicting hepatitis B surface antigen (HBsAg) clearance is important for chronic hepatitis B (CHB) patients receiving pegylated interferon-alfa (Peg-IFN) therapy. We aimed to determine the predictive value of serum hepatitis B core antibody (anti-HBc) for HBsAg clearance. A total of 189 HBeAg-negative CHB patients who received Peg-IFN based therapy were retrospectively included and classified into two groups: nucleos(t)ide analogues (NAs) add-on Peg-IFN group (add-on group, n = 94) and Peg-IFN combined with NAs or Peg-IFN monotherapy group (combination or monotherapy group, n = 95). After 48 weeks of treatment, 27.5% (52/189) and 15.9% (30/189) of patients achieved HBsAg clearance and seroconversion, respectively. Patients in the combination or monotherapy group tended to achieve relatively higher HBsAg clearance (31.6% vs. 23.4%, p = 0.208) and seroconversion (21.1% vs. 10.6%, p = 0.050) rates than those in the add-on group. In combination or monotherapy group, anti-HBc levels at week 12 were lower in patients with HBsAg clearance (9.0 S/CO vs. 9.9 S/CO, p < 0.001) and seroconversion (8.8 S/CO vs. 9.8 S/CO, p < 0.001) than those without. Anti-HBc level at week 12 was an independent predictor of HBsAg clearance and seroconversion. Patients with lower anti-HBc levels at week 12 showed a more significant decline in HBsAg levels during treatment. Combination of anti-HBc at week 12 and baseline HBsAg could identify over 70% of patients who achieved HBsAg clearance after 48 weeks of treatment. In addition to HBsAg, anti-HBc level could be used as a promising marker for selecting HBeAg-negative CHB patients who are more likely to respond to Peg-IFN-based therapy.
Assuntos
Antivirais , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Hepatite B Crônica , Interferon-alfa , Humanos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Hepatite B Crônica/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Masculino , Feminino , Adulto , Estudos Retrospectivos , Anticorpos Anti-Hepatite B/sangue , Antivirais/uso terapêutico , Pessoa de Meia-Idade , Antígenos E da Hepatite B/sangue , Interferon-alfa/uso terapêutico , Vírus da Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Resultado do Tratamento , Quimioterapia Combinada , Soroconversão , Adulto Jovem , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/imunologiaRESUMO
OBJECTIVE: Selected populations of patients with chronic hepatitis B (CHB) may benefit from a combined use of pegylated interferon-alpha (pegIFN-α) and nucleos(t)ides (NUCs). The aim of our study was to assess the immunomodulatory effect of pegIFN-α on T and natural killer (NK) cell responses in NUC-suppressed patients to identify cellular and/or serological parameters to predict better T cell-restoring effect and better control of infection in response to pegIFN-α for a tailored application of IFN-α add-on. DESIGN: 53 HBeAg-negative NUC-treated patients with CHB were randomised at a 1:1 ratio to receive pegIFN-α-2a for 48 weeks, or to continue NUC therapy and then followed up for at least 6 months maintaining NUCs. Serum hepatitis B surface antigen (HBsAg) and hepatitis B core-related antigen (HBcrAg) levels as well as peripheral blood NK cell phenotype and function and HBV-specific T cell responses upon in vitro stimulation with overlapping HBV peptides were measured longitudinally before, during and after pegIFN-α therapy. RESULTS: Two cohorts of pegIFN-α treated patients were identified according to HBsAg decline greater or less than 0.5 log at week 24 post-treatment. PegIFN-α add-on did not significantly improve HBV-specific T cell responses during therapy but elicited a significant multispecific and polyfunctional T cell improvement at week 24 post-pegIFN-α treatment compared with baseline. This improvement was maximal in patients who had a higher drop in serum HBsAg levels and a lower basal HBcrAg values. CONCLUSIONS: PegIFN-α treatment can induce greater functional T cell improvement and HBsAg decline in patients with lower baseline HBcrAg levels. Thus, HBcrAg may represent an easily and reliably applicable parameter to select patients who are more likely to achieve better response to pegIFN-α add-on to virally suppressed patients.
Assuntos
Antivirais , Antígenos E da Hepatite B , Hepatite B Crônica , Interferon-alfa , Células Matadoras Naturais , Polietilenoglicóis , Proteínas Recombinantes , Humanos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/imunologia , Hepatite B Crônica/sangue , Interferon-alfa/uso terapêutico , Antivirais/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Feminino , Adulto , Masculino , Polietilenoglicóis/uso terapêutico , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Pessoa de Meia-Idade , Antígenos E da Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Quimioterapia Combinada , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Resultado do Tratamento , Nucleosídeos/uso terapêuticoRESUMO
A transfusion-transmitted hepatitis B virus (HBV) infection caused by blood only positive for anti-hepatitis B surface antigen (anti-HBs) was reported. Occult HBV infection (OBI) with sole anti-HBs among blood donors is an issue. The incidence of HBV infection among repeat blood donors was investigated with a detailed HBV infection phase, focusing on the influence of anti-HBs level. This study followed 3 435 653 donors for HBV DNA conversion over 4 years and 9 months. Infection phase was determined based on marker changes over DNA conversion. This study identified 115 hepatitis B surface antigen (HBsAg) conversions, 72 DNA-only conversions, and 15 DNA plus anti-hepatitis B core (anti-HBc) conversions among donors all negative for HBV DNA, HBsAg, and anti-HBc. Total incidence was 2.38/100 000 person-years (PY). None of these 202 new HBV infections arose in the group with anti-HBs titer ≥ 10 mIU/mL. In total, 30 anti-HBc-negative OBIs were identified (incidence; 0.35/100 000 PY); 7 showed typical secondary anti-HBs response, and 23 showed stable anti-HBc and anti-HBs levels at DNA conversion. The HBV infection-protective ability of anti-HBs ≥ 10 mIU/mL was reinforced. In addition to new infections, the blood donor population includes anti-HBc-positive- and negative OBI with immune reactions or abortive HBV infection.
Assuntos
Doadores de Sangue , DNA Viral , Anticorpos Anti-Hepatite B , Antígenos do Núcleo do Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Hepatite B , Humanos , Doadores de Sangue/estatística & dados numéricos , Incidência , Hepatite B/epidemiologia , Hepatite B/sangue , Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Masculino , Anticorpos Anti-Hepatite B/sangue , Feminino , Adulto , DNA Viral/sangue , Japão/epidemiologia , Pessoa de Meia-Idade , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Adulto Jovem , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/genética , População do Leste AsiáticoRESUMO
BACKGROUND: The objective of antiviral therapy for chronic viral hepatitis B infection (CHB) is to achieve a functional cure. An important viral marker in the serum of patients with CHB is the serum hepatitis B core-related antigen (HBcrAg). However, there is limited research on HBcrAg in juvenile patients with CHB. In this study, we aimed to investigate the correlation between serum HBcrAg and other hepatitis B virus (HBV) markers in children with CHB and its predictive significance for prognosis during antiviral therapy. METHODS: A single-center retrospective study was conducted involving 79 children with CHB, aged between 0 and 16 years. All the children were treated with interferon [or combined nucleos(t)ide analogs] for 48 weeks. HBcrAg, hepatitis B surface antigen (HBsAg), and HBV DNA were measured before treatment, and at 12 and 48 weeks after treatment. The enrolled children were classified into the seroclearance group and the nonseroclearance group based on the therapeutic outcome. RESULTS: HBsAg seroclearance was observed in 28 out of 79 patients and hepatitis B e antigen seroconversion without HBsAg seroclearance was observed in 14 out of 79 patients following the conclusion of the treatment, with baseline HBcrAg titer levels showing no statistical significance in both the seroclearance and nonseroclearance groups ( P â =â 0.277). HBsAg and HBV DNA were positively correlated with HBcrAg in children with CHB ( R2 â =â 0.3289, 0.4388). The area under the receiver operating characteristic curve of the decrease in HBcrAg at 12 weeks of treatment as a predictor of seroclearance at 48 weeks of treatment, exhibited a value of 0.77. CONCLUSION: A decrease in serum HBcrAg levels in children with hepatitis B serves as a prognostic indicator.
Assuntos
Antivirais , Biomarcadores , DNA Viral , Antígenos do Núcleo do Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Hepatite B Crônica , Humanos , Criança , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/sangue , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Feminino , Masculino , Antivirais/uso terapêutico , Estudos Retrospectivos , Pré-Escolar , Lactente , Adolescente , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Biomarcadores/sangue , Antígenos E da Hepatite B/sangue , DNA Viral/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/genética , Resultado do Tratamento , Curva ROC , Valor Preditivo dos Testes , Recém-Nascido , SoroconversãoRESUMO
Hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg) have been reported to reflect the transcriptional activity of covalently closed circular HBV DNA. We retrospectively investigated the proportions of quantifiable serum HBV RNA and immunoassay for total antigen including complex via pretreatment-hepatitis B core-related antigen (iTACT-HBcrAg) in chronic hepatitis B patients negative for hepatitis B e antigen (HBeAg) and/or with hepatitis B surface antigen (HBsAg) seroclearance. This study included 246 HBeAg-negative HBV-infected patients, who comprised 13 with liver cirrhosis (LC, the LC group), 118 chronic hepatitis (CH, the CH group), and 115 inactive carriers (IC, the IC group), and 44 patients with HBsAg seroclearance. iTACT-HBcrAg and HBV RNA levels were determined using stored serum samples. Higher proportions of the patients had quantifiable iTACT-HBcrAg than HBV RNA in all groups of HBeAg-negative patients (iTACT-HBcrAg: 84.6%, 90.7%, 35.7%, HBV RNA: 23.1%, 26.3%, 14.8%, for the LC, CH, IC groups). With HBsAg seroclearance (HBsAg <0.05 IU/mL), the proportions of quantifiable samples for HBV RNA were also lower than iTACT-HBcrAg (0% for HBV RNA). Thus, iTACT-HBcrAg was more often detectable than circulating HBV RNA in this study population. Further long-term prospective evaluation of iTACT-HBcrAg is desirable for its utilization in clinical practice.
Assuntos
Antígenos do Núcleo do Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Vírus da Hepatite B , Hepatite B Crônica , RNA Viral , Humanos , Hepatite B Crônica/virologia , Hepatite B Crônica/sangue , Masculino , Feminino , Antígenos de Superfície da Hepatite B/sangue , RNA Viral/sangue , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/isolamento & purificação , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Idoso , Imunoensaio/métodosRESUMO
During chronic hepatitis B virus (HBV) infection, the seroclearance of hepatitis B e antigen (HBeAg) is an important event and a significant surrogate endpoint of all current therapeutic strategies. The prediction of HBeAg seroclearance can help assess the benefits of therapy in patients during or before therapy initiation. The quantitation of HBV core antibodies (qAnti-HBc) is a new non-invasive biomarker for solving multiple diagnostic dilemmas. A systematic review and meta-analysis of studies that measured qAnti-HBc in patients who achieved HBeAg seroclearance were performed through PubMed, Web of Science (WoS) and SCOPUS electronic database searches. Nineteen articles were included in the systematic review, comprising 3434 chronically infected patients (1014 with and 2420 without HBeAg seroclearance). Sixteen publications with data regarding qAnti-HBc levels were included in the meta-analysis. The baseline level of qAnti-HBc antibodies was significantly higher in patients with than without HBeAg seroclearance (SMD = 0.88, 95%CI SMD = 0.56-1.2, p < 0.001). The same conclusion was reached for patients originating from Asia (SMD = 0.94, 95%CI SMD = 0.55-1.33) and for the qAnti-HBc antibodies among adult HBV patients with therapy-induced HBeAg seroclearance (SMD = 0.90, 95%CI SMD = 0.54-1.25, p < 0.001). The systematic review and meta-analysis provide evidence of the role of qAnti-HBc as a promising biomarker for predicting HBeAg seroclearance in chronically infected patients.
Assuntos
Biomarcadores , Anticorpos Anti-Hepatite B , Antígenos E da Hepatite B , Vírus da Hepatite B , Hepatite B Crônica , Humanos , Antígenos E da Hepatite B/sangue , Antígenos E da Hepatite B/imunologia , Anticorpos Anti-Hepatite B/sangue , Anticorpos Anti-Hepatite B/imunologia , Biomarcadores/sangue , Hepatite B Crônica/imunologia , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/virologia , Hepatite B Crônica/sangue , Prognóstico , Vírus da Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/sangueRESUMO
BACKGROUND: Occult hepatitis B infection (OBI) refers to the presence of hepatitis B virus (HBV) DNA in the serum or liver of individuals who tested negative for HBV surface antigen (HBsAg). This study aimed to determine seropositivity for antibodies against HBV core antigen (anti-HBc) and the frequency of OBI among the HBsAg non-reactive blood donors in Mashhad, northeastern Iran. METHODS: In this cross-sectional study, serum samples of HBsAg-negative blood donors were examined for anti-HBc during June and August 2018. Anti-HBc-positive samples were tested for antibodies against HBsAg (anti-HBs), and those with negative results were classified as isolated anti-HBc cases. The presence of HBV DNA in the C, S, and X gene regions was assessed by a qualitative real-time polymerase chain reaction method in all HBsAg-negative samples. OBI subjects were detected by the presence of at least one HBV genomic region. RESULTS: Of 540 HBsAg-negative donors, 29 (5.4%; 95% confidence interval: 3.6-7.6%) showed seroreactivity for anti-HBc, of whom 18 individuals were also seropositive for anti-HBs. All donors showed negative results for all three HBV genes regardless of their serum anti-HBc status. CONCLUSION: Based on our findings, we suggest routine screening of Iranian blood donation volunteers for serum anti-HBc and anti-HBs but not HBV DNA.
Assuntos
Doadores de Sangue , DNA Viral , Anticorpos Anti-Hepatite B , Antígenos do Núcleo do Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Hepatite B , Humanos , Estudos Transversais , Irã (Geográfico)/epidemiologia , Doadores de Sangue/estatística & dados numéricos , DNA Viral/sangue , Adulto , Masculino , Anticorpos Anti-Hepatite B/sangue , Hepatite B/epidemiologia , Hepatite B/sangue , Feminino , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Pessoa de Meia-Idade , Adulto Jovem , Prevalência , AdolescenteRESUMO
This study evaluated the diagnostic and analytical performances of the Access anti-HBc Total assay on the DxI 9000 Access Immunoassay System (Beckman Coulter Inc.). The multicenter study involved both prospective and retrospective sample collection from non-selected blood donors, hospitalized patients, or presumed anti-HBc Total positive individuals. Fresh/previously-frozen samples were tested with the Access and comparator assays to determine concordance; discrepant samples were tested with a second CE-marked assay. Among the 5983 non-selected fresh blood donor samples deemed anti-HBc Total negative, clinical specificity of the Access assay was 99.58% (95%CI: 99.38-99.72%). Clinical specificity was 99.27% (97.37-99.80%) among 273 anti-HBc Total negative hospitalized patient samples. Clinical sensitivity on 450 anti-HBc Total positive samples was 99.78% (98.75-99.96%). Evaluation in seroconversion panels revealed an average 1.4-day earlier detection versus a comparator assay. The Access assay demonstrated excellent clinical and analytical performances comparable to existing CE-marked anti-HBc Total assays. NCT04904835.
Assuntos
Anticorpos Anti-Hepatite B , Sensibilidade e Especificidade , Humanos , Imunoensaio/métodos , Imunoensaio/normas , Estudos Prospectivos , Estudos Retrospectivos , Anticorpos Anti-Hepatite B/sangue , Hepatite B/diagnóstico , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Doadores de Sangue , Feminino , Masculino , Adulto , Pessoa de Meia-IdadeRESUMO
Hepatitis B core-related antigen (HBcrAg) reflects the activity of intrahepatic covalently closed circular DNA. HBcrAg can be detected even in chronic hepatitis B patients in whom serum HBV DNA or hepatitis B surface antigen is undetectable. The HBcrAg measurement system was developed based on two concepts. One is a fully-automated and highly-sensitive HBcrAg assay (iTACT-HBcrAg) and the other is a point-of-care testing (POCT) that can be used in in resource-limited areas. iTACT-HBcrAg is an alternative to HBV DNA for monitoring HBV reactivation and predicting the development of hepatocellular carcinoma. This validated biomarker is available in routine clinical practice in Japan. Currently, international guidelines for the prevention of mother-to-child transmission recommend anti-HBV prophylaxis for pregnant women with high viral loads. However, over 95% of HBV-infected individuals live in countries where HBV DNA quantification is widely unavailable. Given this situation, a rapid and simple HBcrAg assay for POCT would be highly effective. Long-term anti-HBV therapy may have potential side effects and appropriate treatment should be provided to eligible patients. Therefore, a simple method of determining the indication for anti-HBV treatment would be ideal. This review provides up-to-date information regarding the clinical value of HBcrAg in HBV management, based on iTACT-HBcrAg or POCT.
Assuntos
Antígenos do Núcleo do Vírus da Hepatite B , Vírus da Hepatite B , Humanos , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , DNA Viral/sangue , Hepatite B/diagnóstico , Hepatite B/virologia , Biomarcadores/sangue , Sensibilidade e Especificidade , Testes Imediatos , Programas de Rastreamento/métodos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/virologia , Feminino , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/virologia , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Carga Viral , Gravidez , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/virologia , Antígenos de Superfície da Hepatite B/sangueRESUMO
This study aimed to assess the predictive capacity of emerging serological markers, serum HBV RNA and HBcrAg, for HBeAg seroconversion in children with HBeAg-positive chronic hepatitis B (CHB). Treatment-naïve HBeAg-positive CHB children who admitted to the Liver Disease Center of Hunan Children's Hospital between April 2021 and September 2022 and received treatment with the combined entecavir and interferon-alpha treatment were recruited. Serum HBV RNA and HBcrAg were measured at baseline and Weeks 12, 24, and 48 of treatment. Our study showed that serum HBV RNA (HR = 0.71, 95% CI: 0.56-0.91, p = 0.006), HBcrAg (HR = 0.60, 95% CI: 0.43-0.84, p = 0.003), and HBsAg (HR = 0.49, 95%CI: 0.36-0.69, p < 0.001) at Week 12 were independent predictors of HBeAg seroconversion. ROC curve analysis presented that serum HBV RNA decline value (ΔHBV RNA) at Week 36 and HBcrAg decline value (ΔHBcrAg) at Week 12 (AUC = 0.871, p = 0.003 and AUC = 0.810, p = 0.003, respectively) could effectively predict HBeAg seroconversion. Furthermore, the optimal critical values were determined and the children with ΔHBV RNA > 3.759 log10 copies/mL at Week 36 or ΔHBcrAg >0.350 log10 U/mL at Week 12 more likely to achieve HBeAg seroconversion. The serum HBV RNA and HBcrAg provide new insights into the treatment of CHB in children. Early assessment of serum HBV RNA and HBcrAg during treatment can assist clinical decision-making and optimize individualized therapeutic approaches.
Assuntos
Antivirais , Antígenos E da Hepatite B , Vírus da Hepatite B , Hepatite B Crônica , RNA Viral , Soroconversão , Humanos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Hepatite B Crônica/sangue , Masculino , Feminino , Criança , Antígenos E da Hepatite B/sangue , Antivirais/uso terapêutico , RNA Viral/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Adolescente , Interferon-alfa/uso terapêutico , Pré-Escolar , Biomarcadores/sangue , Guanina/uso terapêutico , Guanina/análogos & derivados , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Curva ROCRESUMO
BACKGROUND: Hepatitis B caused by hepatitis B virus (HBV) infection is a serious global public health issue. Currently, serological indicators serve as important markers for the diagnosis of hepatitis B. It has been found that HBV core-related antigen (HBcrAg) correlates well with intrahepatic cccDNA, intrahepatic HBV DNA, serum HBV DNA, and hepatitis B e antigen (HBeAg). To provide a more reliable basis for the diagnosis and treatment of hepatitis B, we explored the correlation between HBcrAg and conventional serologic testing indicators and disease staging. METHODS: Five hundred forty-two patient serum samples were collected at the First Affiliated Hospital of Soochow University from November 2021 to March 2022. The serum HBcrAg was measured by the magnetic particle chemiluminescence method in addition with other serum indicators. RESULTS: HBcrAg statistically correlated with HBV DNA level (r = 0.655, p < 0.001) and HBeAg level (r = 0.945, p < 0.001. The mean HBcrAg levels in the immune-tolerant and immune-clearance phases were significantly higher than those in the immunologic-control phase and the reactivation phase. This study demonstrated that serum HBcrAg positively correlated with serum HBV DNA and HBeAg. Even in cases where HBV DNA and HBeAg are negative, there is still a higher positivity rate of HBcrAg in hepatitis B patients. CONCLUSIONS: HBcrAg is a reliable serum marker to avoid underdiagnosis of occult HBV infection.
Assuntos
Biomarcadores , DNA Viral , Antígenos do Núcleo do Vírus da Hepatite B , Antígenos E da Hepatite B , Vírus da Hepatite B , Hepatite B , Humanos , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Masculino , Feminino , Hepatite B/diagnóstico , Hepatite B/imunologia , Hepatite B/sangue , Hepatite B/virologia , Antígenos E da Hepatite B/sangue , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/genética , Adulto , Biomarcadores/sangue , Pessoa de Meia-Idade , DNA Viral/sangue , Adulto Jovem , Idoso , AdolescenteRESUMO
Hepatitis B virus reactivation (HBV-R) is a serious complication that can occur in patients with resolved HBV infection during cancer chemotherapy. We examined the levels of HBV surface antibody (HBsAb) and HBV core antibody (HBcAb) to assess the incidence of HBV-R in cancer patients including hematopoietic stem cell transplantation (HSCT) and rituximab administration. This retrospective cohort study included 590 patients with resolved HBV infection. The incidence of HBV-R was evaluated 761.5 (range, 90-3898) days after the inititiation of chemotherapy. Of the patients, 13 (2.2%) developed HBV-R after the start of chemotherapy. All 13 patients exhibited lower HBsAb (<100 mIU/mL) levels at baseline. A higher level of HBcAb (≥100 cut off index (C.O.I.)) was a possible risk factor for HBV-R as well as HSCT and rituximab administration. The simultaneous presence of HBsAb <100 mIU/mL and HBcAb ≥100 C.O.I. increased the risk of HBV-R by 18.5%. Patients treated with rituximab were at a higher risk of HBV-R (18.4%) despite having HBcAb <100 C.O.I. Our results suggest that assessment of HBsAb and HBcAb levels prior to the chemotherapy is important for identifying patients at high risk of HBV-R, especially in solid cancers without HSCT and rituximab administration.
Assuntos
Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Hepatite B , Rituximab , Ativação Viral , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Anticorpos Anti-Hepatite B/sangue , Anticorpos Anti-Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/fisiologia , Ativação Viral/efeitos dos fármacos , Rituximab/uso terapêutico , Rituximab/efeitos adversos , Adulto , Idoso , Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Adulto Jovem , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Idoso de 80 Anos ou mais , AdolescenteRESUMO
BACKGROUND AND AIM: The purpose of the current study was to investigate the predictive value of hepatitis B core-related antigen (HBcrAg) on the occurrence and recurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). METHODS: We searched PubMed, Embase, Scopus, and Web of Science from database inception to April 6, 2023. Pooled hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) was calculated for the occurrence and recurrence of HCC. RESULTS: Of the 464 articles considered, 18 articles recruiting 10 320 patients were included. The pooled results showed that high serum HBcrAg level was an independent risk factor for the occurrence of HCC in CHB patients (adjusted HR = 3.12, 95% CI: 2.40-4.06, P < 0.001, I2 = 43.2%, P = 0.043; OR = 5.65, 95% CI: 3.44-5.82, P < 0.001, I2 = 0.00%, P = 0.42). Further subgroup analysis demonstrated that the predictive ability of HBcrAg for the occurrence of HCC is not influenced by the hepatitis B e antigen (HBeAg) status or the use of nucleoside/nucleotide analogs (NAs). In addition, our meta-analysis also suggests that HBcrAg is a predictor of HCC recurrence (adjusted HR = 1.71, 95% CI: 1.26-2.32, P < 0.001, I2 = 7.89%, P = 0.031). CONCLUSIONS: For patients with CHB, serum HBcrAg may be a potential predictive factor for the occurrence of HCC, regardless of HBeAg status or NA treatment. It may also serve as a novel prognostic biomarker for the recurrence of HCC. More studies are needed to confirm our conclusions.
Assuntos
Carcinoma Hepatocelular , Antígenos do Núcleo do Vírus da Hepatite B , Hepatite B Crônica , Neoplasias Hepáticas , Recidiva Local de Neoplasia , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/etiologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/virologia , Humanos , Hepatite B Crônica/complicações , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Fatores de Risco , Valor Preditivo dos Testes , Antígenos E da Hepatite B/sangue , Masculino , Feminino , Biomarcadores Tumorais/sangueRESUMO
Hepatitis B virus (HBV) infection is a serious global health problem, and chronic HBV infection significantly increases the risk of liver fibrosis, cirrhosis, and even hepatocellular carcinoma in patients. Current first-line therapeutics such as nucleos(t)ide analogues and interferons are unable to completely clear cccDNA, so the vast majority of patients need to take long-term or even lifelong medication. However, long-term virological and biochemical responses can be achieved in some patients after drug withdrawal. Successfully screening these patients with drug withdrawal advantages is difficult. Hepatitis-B-core-related antigen (HBcrAg) is a new HBV serological marker that which can reflect the level and transcription activity of cccDNA in hepatocytes. Therefore, HBcrAg has potential value in guiding patients in drug withdrawal. This review summarizes previous reports on HBcrAg and evaluates the application value of HBcrAg in safe drug discontinuation.
Assuntos
Antivirais , Antígenos do Núcleo do Vírus da Hepatite B , Vírus da Hepatite B , Hepatite B Crônica , Humanos , Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/efeitos dos fármacos , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Biomarcadores/sangue , Suspensão de Tratamento , DNA Viral/sangueRESUMO
BACKGROUND AND OBJECTIVES: Exclusion of blood donors with hepatitis B virus (HBV) core antibodies (anti-HBc) prevents transfusion-transmitted HBV infection but can lead to significant donor loss. As isolated anti-HBc positivity does not always indicate true past HBV infection, we have investigated the effectiveness of confirmatory anti-HBc testing and the representation of rare blood groups in anti-HBc-positive donors. MATERIALS AND METHODS: Three hundred ninety-seven HBV surface antigen-negative and anti-HBc initially reactive blood donor samples were tested by five different anti-HBc assays. RESULTS: Eighty percentage of samples reactive in Architect anti-HBc assay were positive by the Murex assay and anti-HBc neutralization. Eleven out of 397 samples showed discordant results in supplementary testing from the Murex confirmatory test result, and five remained undetermined following extensive serological testing. Thirty-eight percentage of anti-HBc-positive donors identified as minority ethnic groups compared with 11% representation in anti-HBc-negative donors (p < 0.0001); the frequency of the Ro blood group in anti-HBc-positive donors was 18 times higher in non-white ethnic groups. CONCLUSION: Using two anti-HBc assays effectively enabled the identification of HBV-exposed and potentially infectious donors, their deferral and potential clinical follow-up. However, the exclusion of confirmed anti-HBc-positive donors will still impact the supply of rare blood such as Ro.
Assuntos
Doadores de Sangue , Anticorpos Anti-Hepatite B , Antígenos do Núcleo do Vírus da Hepatite B , Vírus da Hepatite B , Hepatite B , Humanos , Anticorpos Anti-Hepatite B/sangue , Hepatite B/sangue , Hepatite B/prevenção & controle , Feminino , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Masculino , Vírus da Hepatite B/imunologia , Seleção do Doador/métodos , Antígenos de Grupos Sanguíneos/imunologia , Doação de SangueRESUMO
BACKGROUND & AIMS: The contribution of the novel biomarkers, hepatitis B virus (HBV) RNA and HBV core-related antigen (HBcrAg), to characterization of HBV-human immunodeficiency virus (HIV) coinfection is unclear. We evaluated the longitudinal dynamics of HBV RNA and HBcrAg and their association with classical HBV serum biomarkers and liver histology and viral staining. METHODS: HBV-HIV co-infected adults from 8 North American centers entered a National Institutes of Health-funded prospective cohort study. Demographic, clinical, serological, and virological data were collected at entry and every 24 to 48 weeks for up to 192 weeks. Participants with HBV RNA and HBcrAg measured ≥2 times (N = 95) were evaluated; 56 had paired liver biopsies obtained at study entry and end of follow-up. RESULTS: Participants had a median age of 50 years; 97% were on combination anti-viral therapy. In hepatitis B e antigen (HBeAg)+ participants, there were significant declines in HBV RNA and HBcrAg over 192 weeks that tracked with declines in HBeAg, hepatitis B surface antigen, HBV DNA, and hepatitis B core antigen (HBcAg) hepatocyte staining grade (all P < .05). In HBeAg- participants, there were not significant declines in HBV RNA (P = .49) and HBcrAg (P = .63), despite modest reductions in hepatitis B surface antigen (P < .01) and HBV DNA (P = .03). HBV serum biomarkers were not significantly related to change in hepatic activity index, Ishak fibrosis score, or hepatocyte HBcAg loss (all P > .05). CONCLUSIONS: In HBV-HIV coinfected adults on suppressive dually active antiviral therapy, the use of novel HBV markers reveals continued improvement in suppression of HBV transcription and translation over time. The lack of further improvement in HBV serum biomarkers among HBeAg- patients suggests limits to the benefit of combination anti-viral therapy and provide rationale for additional agents with distinct mechanisms of action.
Assuntos
Coinfecção , Infecções por HIV , Antígenos do Núcleo do Vírus da Hepatite B , Vírus da Hepatite B , Hepatite B Crônica , Replicação Viral , Adulto , Humanos , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Biomarcadores/sangue , Coinfecção/diagnóstico , DNA Viral , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Estudos Prospectivos , RNA Viral/sangueRESUMO
Serum hepatitis B core-related antigen (HBcrAg) and surface antigen (HBsAg) are surrogate markers of intrahepatic covalently closed circular DNA. The measurement range of the current HBcrAg assay is relatively narrow. Thus, we examined the potential of HBcrAg and HBsAg measured by ultrasensitive assays for predicting hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B treated with entecavir (ETV). We conducted a retrospective cohort study of 180 patients who received ETV for >1 year. All patients had hepatitis B e-antigen negativity at baseline. Serum HBcrAg and HBsAg levels at baseline and year 1 were measured in all patients by ultrasensitive assays using immunoassay for total antigen including complex by pretreatment (iTACT) technology. During the median follow-up of 11.0 years, 22 patients developed HCC (11.8/1,000 person-years). Baseline HBsAg levels were not associated with HCC development during ETV treatment. However, high HBcrAg levels at baseline and at year 1 were significantly associated with HCC development (log-rank test; P < 0.001). In 110 patients (61.1%) with ≥4.0 log U/mL at baseline (high HBcrAg cohort), HBcrAg declined to ≤2.9 log U/mL at year 1 in 25 patients (22.7%). The adjusted hazard ratio for HCC incidence was significantly lower in patients with HBcrAg ≤2.9 log U/mL at year 1 than in those in the high HBcrAg cohort. Conclusion: Measurement of HBcrAg by ultrasensitive assay has better potential for predicting HCC during antiviral treatment than the current HBcrAg assay.
Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/diagnóstico , Guanina/análogos & derivados , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Imunoensaio , Neoplasias Hepáticas/diagnóstico , Biomarcadores Tumorais/sangue , DNA Circular/sangue , Feminino , Guanina/uso terapêutico , Hepatite B Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Introducción. La seguridad transfusional es el objetivo primordial de los bancos de sangre, sin embargo, conlleva un alto riesgo de eventos adversos como son las infecciones transmisibles por transfusión (ITT). El conocimiento de la prevalencia de estas infecciones fue de particular interés en esta investigación, donde se determinó su frecuencia, coinfección y relación con el tipo de donantes admitidos. Metodología. Estudio observacional retrospectivo de 2017 y 2018, en el que se incluyeron todos los registros de donantes de sangre que contenían datos demográficos y resultados de los marcadores obligatorios en el país (Ecuador), tanto de pruebas serológicas como moleculares. Se obtuvo el permiso del custodio de la información y del subcomité de bioética de investigaciones en seres humanos. Para el análisis de los datos se utilizó estadística descriptiva e inferencial. Resultados. Se determinó una prevalencia del 3,18 % de resultados reactivos para una o más ITT, el rango de edad más prevalente fue de 29 a 40 años, el 89,8 % fueron donantes compensatorios, y de ellos el 90 % fueron reactivos para una o más ITT. El marcador serológico más prevalente fue el anti-core del virus de la hepatitis B (anti-HBc), seguido por el de sífilis y los anticuerpos contra el virus de la hepatitis C (VHC). La coinfección más prevalente fue con sífilis y hepatitis B. Se encontró una diferencia estadísticamente significativa entre los resultados obtenidos en las pruebas serológicas y las moleculares (x2=26,9; p=0,000). Conclusión. Las ITT en los bancos de sangre son un riesgo latente, por lo que es necesario conocer las variaciones epidemiológicas que existen en cada población. El conocimiento de la prevalencia de las ITT en donantes de sangre permite establecer nuevas estrategias de selección del donante, que garanticen la mejor seguridad posible en las transfusiones, además debe verificarse siempre la metodología utilizada y hacer monitoreo permanente del sistema de calidad establecido
Introduction. Transfusion safety is the primary objective of blood banks, however one of the adverse reactions to blood transfusion are the transfusion transmissible infections (TTIs). Knowledge of the prevalence of these infections was of particular interest in this study where we determined their frequency, co-infection and relationship with the type of donors admitted. Methodology. Retrospective observational study during 2017 and 2018, in which all blood donor records containing demographic data and results of the country's (Ecuador) mandatory serological markers of both serological and molecular tests were included. Permission was obtained from the data custodian and the Human Research Bioethics Subcommittee. Descriptive and inferential statistics were used for data analysis. Results. A prevalence of 3,18% of reactive results to one or more TTIs was determined, the most prevalent age range was 29 to 40 years, 89.8% were compensatory donors and 90% of them were reactive to one or more TTIs. The anti- core serological marker of the hepatitis B virus (anti-HBc) was the most prevalent, followed by syphilis and hepatitis C antibodies. Syphilis and hepatitis B were identified as the most prevalent coinfection. The correlation between the results obtained in the serological and molecular tests was determined to be different and statistically significant (x2=26.9; p=0.000). Conclusion. TTIs in blood banks are a latent risk, so it is necessary to know the epidemiological variations that exist in every population. Knowledge of the prevalence of TTIs in blood donors facilitates new donor selection strategies that guarantee the best possible safety in transfusions. In addition, the methodology used must always be verified and the established quality system must be permanently monitored
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Doadores de Sangue , Transfusão de Sangue , Infecções Transmitidas por Sangue/epidemiologia , Sífilis/sangue , Sífilis/epidemiologia , Estudos Soroepidemiológicos , Prevalência , Estudos Retrospectivos , Hepatite C/sangue , Hepatite C/epidemiologia , Hepatite B/sangue , Hepatite B/epidemiologia , Antígenos do Núcleo do Vírus da Hepatite B/sangueRESUMO
Therapy with nucleic acid polymers (NAPs), tenofovir disoproxil fumarate (TDF), and pegylated interferon (pegIFN) achieve high rates of HBsAg loss/seroconversion and functional cure in chronic hepatitis B virus (HBV) infection. The role of hepatitis B surface antigen (HBsAg) seroconversion and inactivation of covalently closed circular DNA (cccDNA) in establishing functional cure were examined. Archived serum from the REP 401 study was analyzed using the Abbott ARCHITECT HBsAg NEXT assay (Chicago, IL), Abbott research use-only assays for HBsAg immune complexes (HBsAg ICs), circulating HBV RNA, and the Fujirebio assay for hepatitis B core-related antigen (HBcrAg; Malvern, PA). HBsAg became < 0.005 IU/mL in 23 participants during NAP exposure, which persisted in all participants with functional cure. HBsAg IC declined during lead-in TDF monotherapy and correlated with minor declines in HBsAg. Following the addition of NAPs and pegIFN, minor HBsAg IC increases (n = 13) or flares (n = 2) during therapy were not correlated with HBsAg decline, hepatitis B surface antibody (anti-HBs) titers, or alanine aminotransferase. HBsAg IC universally declined during follow-up in participants with virologic control or functional cure. Universal declines in HBV RNA and HBcrAg during TDF monotherapy continued with NAP + pegIFN regardless of therapeutic outcome. At the end of therapy, HBV RNA was undetectable in only 5 of 14 participants with functional cure but became undetectable after removal of therapy in all participants with functional cure. Undetectable HBV RNA at the end of therapy in 5 participants was followed by relapse to virologic control or viral rebound. Conclusion: Anti-HBs-independent mechanisms contribute to HBsAg clearance during NAP therapy. Inactivation of cccDNA does not predict functional cure following NAP-based therapy; however, functional cure is accompanied by persistent inactivation of cccDNA. Persistent HBsAg loss with functional cure may also reflect reduction/clearance of integrated HBV DNA. Clinicaltrials.org number NCT02565719.
Assuntos
Antivirais/uso terapêutico , DNA Circular/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/imunologia , Soroconversão/efeitos dos fármacos , Adulto , Alanina Transaminase/sangue , Alanina Transaminase/efeitos dos fármacos , Estudos Cross-Over , DNA Circular/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/efeitos dos fármacos , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/tratamento farmacológico , Humanos , Interferons/uso terapêutico , Masculino , Ácidos Nucleicos/uso terapêutico , Polímeros/uso terapêutico , RNA Viral/sangue , RNA Viral/efeitos dos fármacos , RNA Viral/imunologia , Tenofovir/uso terapêutico , Resultado do Tratamento , Inativação de Vírus/efeitos dos fármacosRESUMO
BACKGROUND: Clinical importance of commercially available quantitative HBV markers has not been fully investigated. OBJECTIVE: To choice and to evaluate clinically valuable HBV markers for predicting phases of natural history with chronic HBV infection. METHODS: 472 naïve patients with chronic HBV infection were enrolled, in which 21 and 220 were confirmed as HBeAg-positive inactive and active hepatitis (EPIH and EPAH), respectively, and 106 and 125 were confirmed as HBeAg-negative inactive and active hepatitis (ENIH and ENAH), respectively. HBsAg, HBcrAg and anti- HBc were measured using chemiluminescent immunoassay, and HBV DNA was measured using PCR-fluorescence probing assay. RESULTS: There were all statistical differences in medians of HBsAg, anti-HBc, HBcrAg and HBV DNA between EPIH and EPAH and between ENIH and ENAH (all P < 0.01). According to binary logistic stepwise regressions, HBsAg and anti-HBc were preferred variables for predicting EPAH, and HBcrAg and HBV DNA were preferred variables for predicting ENAH. Based on normalization for coefficients of preferred variables entering regression equations, a handy model of MEPAH for predicting EPAH and of MENAH for predicting ENAH was constructed, respectively. Area under receiver operating characteristic curves of MEPAH and MENAH for predicting EPAH and ENAH were 0.882 and 0.931, respectively. With standard of MEPAH ≤ 5.997 and MENAH > 10.535, sensitivity or specificity of which for predicting EPAH and ENAH were about 81.0 % and 87.0 %, respectively. CONCLUSION: HBsAg and anti-HBc for predicting EPAH and HBcrAg and HBV DNA for predicting ENAH are dependable markers; MEPAH for predicting EPAH and MENAH for predicting ENAH have very good performance.