RESUMO
BACKGROUND: Adefovir Dipivoxil (ADV) is an important agent to suppress hepatitis B virus (HBV) replication with suboptimal effect on virological and serological response. To optimize Adefovir therapy in chronic hepatitis B (CHB) patients with hepatitis B e antigen (HBeAg) positive, we studied the baseline parameters and on-treatment HBV DNA for favorable outcomes. METHODS: 48 patients were enrolled in the study and followed up for 5 years prospectively. Baseline characteristics, virological, serological and biochemical parameters as well as on treatment HBV DNA were assessed in prediction of favorable outcomes. RESULTS: 1. The patients with baseline alanine aminotransferase (ALT) ≥5 × the upper limit of normal (ULN, 40 IU/L) had higher rates of viral response (VR), HBeAg loss and HBeAg seroconversion at year 5 compared to the patients with ALT < 5 × ULN (VR: 75% vs 43.8%, p = 0.035; HBeAg loss: 43.9% vs 13.8%, p = 0.017; HBeAg seroconversion: 37.9% vs 13.8%, p = 0.035); Patients with baseline HBV DNA < 10(9) copies/ml and ALT ≥3 × ULN had more chance of HBeAg seroconversion (40.9% vs 8.7%, p = 0.012), while in patients with HBeAg < 800 s/co or HBsAg < 5000 IU/ml higher rates of HBeAg loss were achieved. 2. HBV DNA level < 10(4) copies/ml at week 24 was predictive for VR (96.0% vs 40.9%, P < 0.001), HBeAg loss (84.0% vs 36.3%, P = 0.001) and HBeAg seroconversion (36.0% vs 9.1%, P = 0.030). CONCLUSIONS: ADV treatment should be started for patients with baseline ALT≥5 × ULN or patients with ALT≥3 × ULN and HBV DNA < 10(9) copies/ml. Lower level of HBeAg(< 800 s/co) and HBsAg(< 5000 IU/ml) may be regarded as referenced factors. In patients with serum HBV DNA < 10(4) copies/ml at week 24 the therapy should continue, and a favorable outcome may be achieved in 5 years or longer.
Assuntos
Adenina/análogos & derivados , Alanina Transaminase/análise , Antivirais/administração & dosagem , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/imunologia , Organofosfonatos/administração & dosagem , Adenina/administração & dosagem , Adenina/uso terapêutico , Adulto , Alanina Transaminase/metabolismo , Antivirais/uso terapêutico , Biomarcadores/análise , China , Feminino , Seguimentos , Antígenos de Superfície da Hepatite B/análise , Antígenos de Superfície da Hepatite B/imunologia , Antígenos E da Hepatite B/análise , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/metabolismo , Hepatite B Crônica/virologia , Humanos , Masculino , Organofosfonatos/uso terapêutico , Estudos Prospectivos , Resultado do TratamentoAssuntos
Genótipo , Vírus da Hepatite B/genética , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/virologia , Adolescente , Adulto , Criança , China/epidemiologia , Feminino , Genes Virais , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Isoformas de Proteínas , Adulto JovemRESUMO
BACKGROUND: The early detection of hepatitis B virus (HBV) mutants in clinical samples is important when monitoring chronic HBV patients with lamivudine-resistant mutations during lamivudine therapy. METHODS: The AllGlo™ probes were designed to distinguish between wild-type (YMDD) and mutant (YVDD and YIDD) strains of HBV. The sensitivity and specificity of the assay were evaluated using a series of diluted mixtures of wild-type and mutant plasmids. This assay was compared with direct sequencing and the mutation-specific primer assay. RESULTS: Each YMDD, YVDD, and YIDD probe only detected its corresponding plasmid. Moreover, the assay correctly identified negative samples from 40 non-HBV infected patients and 100 healthy controls. The detection limit of this assay was 50 copies/ml for YVDD and YIDD. The assay could detect the mutant strains when they were present at ≥10% within a mixed virus population. The assay was fully concordant with direct sequencing in 34 samples (56.7%) and partially concordant in 26 samples (43.3%), and detected more types of the HBV motif than direct sequencing. CONCLUSIONS: AllGlo™ probe assay is a novel, sensitive and specific assay to detect lamivudine-related HBV mutants, therefore, may be useful for monitoring chronic HBV patients treated with lamivudine.