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1.
Exp Ther Med ; 18(6): 4541-4546, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31798696

RESUMO

Hepatitis B virus (HBV) infection represents a public health threat and a challenge for the medical community. Untimely treatment may lead to liver cirrhosis and even liver cancer. At present, the major treatment for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients includes administration of interferon-α (IFN-α), which has anti-viral and immunomodulatory effects. Plasmacytoid dendritic cells (pDCs) and Toll-like receptor-9 (TLR-9) have important roles in anti-viral therapy. However, their predictive value regarding the efficacy of IFN-α treatment of HBeAg-positive chronic hepatitis B (CHB) patients has remained elusive. A total of 178 patients with CHB and HBeAg-positive status, who had not received any previous anti-HBV treatment, were enrolled in the present study. All patients were treated with IFN-α. HBV DNA load, hepatitis B surface antigen and serum alanine aminotransferase were measured prior to and following 48 weeks of treatment. According to HBV levels, the patients were divided into a response group and non-responders group. To determine the amount of pDCs, blood dendritic cell antigen 2 (BDCA-2)- and immunoglobulin-like transcript 7 (ILT7)-expressing cells in liver biopsies were detected using immunohistochemistry. TLR-9 expression in peripheral blood mononuclear cells was determined by reverse transcription-quantitative PCR. There was no significant difference in the proportion of pDCs (BDCA-2; ILT7) and TLR-9 mRNA expression between the response group and the non-responders group prior to IFN-α treatment. After IFN-α treatment, BDCA-2, ILT7 and TLR-9 mRNA expression was obviously increased in the response group compared with that in the non-responders group (P<0.05). Increased expression of BDCA-2, ILT7 and TLR-9 mRNA was negatively correlated with HBV DNA (P<0.05). Increased levels of pDCs and TLR-9 were negatively correlated with HBV DNA, and were thus capable of predicting the IFN-α treatment response in patients with CHB and HBeAg-positive status.

2.
J Clin Transl Hepatol ; 7(3): 249-257, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31608217

RESUMO

Background and Aims: Data are limited on the use of pegylated-interferon alpha-2a (peg-IFNα) in Chinese patients with chronic hepatitis B virus (HBV) infection (CHB). We evaluated the effectiveness and safety of peg-IFNα in Chinese patients with hepatitis B envelope antigen-negative CHB in routine clinical practice. Methods: In this prospective, multicenter, observational, non-interventional cohort study, patients were assessed for up to 1 year after peg-IFNα treatment cessation. Treating physicians established the dosing and treatment duration according to Chinese clinical practice. Effectiveness of peg-IFNα treatment was measured by the percentage of: patients with HBV DNA <2000 IU/mL and loss of hepatitis B surface antigen (commonly known as HBsAg); HBV DNA level at end of treatment (EOT), and 6 months and 1 year posttreatment; and time course change in quantitative HBV DNA and HBsAg. Results: At EOT, 6 months posttreatment, and 1 year posttreatment, the percentage of patients with HBV DNA <2000 IU/mL was 90.0%, 81.8%, and 82.2%, and that of patients with HBsAg loss was 6.5%, 9.4%, and 9.5%, respectively. The HBV DNA level decreased from 5.61 log IU/mL at baseline to 2.48 log IU/mL at EOT and 2.67 log IU/mL at 1 year posttreatment. The HBsAg level decreased from 3.08 log IU/mL at baseline to 2.24 log IU/mL at EOT and 2.10 log IU/mL at 1 year posttreatment. The incidence of adverse events was 52.0%. Conclusions: Peg-IFNα has the potential to provide functional cure (HBsAg loss) for CHB and is well tolerated in hepatitis B envelope antigen-negative CHB patients in routine clinical practice in China. Clinical Trial Registration: ClinicalTrials.gov (NCT01730508).

3.
J Viral Hepat ; 26(9): 1050-1058, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31074081

RESUMO

Ubiquitin-specific protease 18 (USP18) is an important inhibitor of interferon (IFN) antiviral activity, and the aim of this study was to investigate the association between the USP18 mRNA level change in peripheral blood mononuclear cells (PBMCs) when stimulated with IFN in vitro before initiating treatment and the treatment outcomes in HBeAg-positive chronic hepatitis B (CHB) patients treated with IFN. A total of 44 patients who received standard IFN-based anti-HBV therapy and follow-up were enrolled in the study. The in vitro IFN-induced USP18 mRNA change (USP18IFN-N ) was measured via comparison of quantitative PCR-determined USP18 transcription levels of BPMCs cultured with and without IFN stimulation. Either for virological (VR) or serological response (SR), the baseline USP18IFN-N was significantly higher (P = 0.018 for VR, P = 0.008 for SR) among nonresponders (n = 23 for VR, n = 33 for SR) than that of responders (n = 21 for VR, n = 11 for SR). Multivariate analyses revealed baseline USP18IFN-N was a novel independent predictor for either VR (OR = 0.292, 95% CI = 0.102-0.835, P = 0.022) or SR (OR = 0.173, 95% CI = 0.035-0.849, P = 0.031) in our cohort. In addition, baseline USP18IFN-N in combination with HBV DNA loads or HBeAg levels showed improved accuracy of pretreatment prediction for VR or SR responders, respectively. Baseline USP18IFN-N levels are associated with both virological and serological response, and have the potential to become a clinical predictor for treatment outcomes in HBeAg-positive CHB patients before initiating IFN-α therapy.

4.
Aging (Albany NY) ; 8(11): 2862-2870, 2016 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-27824315

RESUMO

Mannose binding lectin (MBL) plays important role in the innate immunity of human. Mutations in the MBL2 gene can significantly change the serum level of MBL, and consequently alter the susceptibility and progression of infectious disease. However, the association between the MBL2 profile and the HBV mutation and quasispecies complexity has not yet been reported. Our approach includes the study of the MBL2 gene genotype as well as ultra-deep sequencing of the HBV viruses obtained from the plasma of 50 treatment naïve patients with chronic HBV infection. We found that the liver function was better among patients within the high MBL2 group with respect to those within the medium/low MBL2 group. Likewise, the number of mutations in the HBV X gene as well as the viral quasispecies complexity were significantly higher in medium/low MBL2 production group. Nucleotide substitution rates were also higher within the medium/low MBL2 production group in all positions described to have an influence in liver cancer development, except for A1499G. In this work we show that the MBL2 profile may have an impact on the HBV X gene mutations as well as on viral quasispecies complexity.


Assuntos
Genes Virais , Haplótipos , Vírus da Hepatite B/genética , Hepatite B/imunologia , Lectina de Ligação a Manose/genética , Mutação , Adulto , Idoso , Progressão da Doença , Feminino , Predisposição Genética para Doença , Hepatite B/genética , Humanos , Imunidade Inata , Masculino , Lectina de Ligação a Manose/sangue , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real/métodos , Adulto Jovem
5.
Sci Rep ; 6: 32147, 2016 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-27557564

RESUMO

The innate immunity gene mannose-binding lectin2 (MBL2) has played an important role in hepatitis B virus (HBV) infection, and the relationship between MBL2 variants and hepatocellular carcinoma (HCC) risk has not yet been identified. In total, 315 HCC cases and 315 healthy controls were enrolled and blood samples were acquired. High resolution melt analysis (HRM) was employed to genotype 6 polymorphisms in MBL2 gene. Increased HCC risk in carriers of LL genotype of -550 polymorphism with an adjusted OR (AOR) of 1.61 (95%CI = 1.00-2.57) was observed but no significant association detected in HL genotype. Both YX and XX genotype demonstrated a significantly elevated HCC risk in the analysis of -221 polymorphism. The B variants in codon 54 was also significantly associated with elevated HCC risk. HYB was identified as the protective factor of HCC while LXB was significantly associated with increase HCC risk. ELISA technique revealed that the MBL2 protein was significantly reduced in HCC cases. Moreover, both IL-1ß and IL-6 were inversely associated with plasma MBL2 level.The mutations in MBL2 could lead to compromised innate immunity, and possibly lead to elevated HCC risk, and a novel haplotype HXB has been identified with a rate of 12.5%.


Assuntos
Carcinoma Hepatocelular/genética , Predisposição Genética para Doença , Haplótipos , Neoplasias Hepáticas/genética , Lectina de Ligação a Manose/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-6/sangue , Neoplasias Hepáticas/patologia , Modelos Logísticos , Masculino , Lectina de Ligação a Manose/sangue , Pessoa de Meia-Idade , Polimorfismo Genético
6.
PLoS One ; 10(7): e0134532, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26230094

RESUMO

To understand the mechanisms underlying the discordance between normal serum alanine aminotransferase (ALT) levels and significant alterations in liver histology of chronic hepatitis B virus (HBV) infection with persistent normal ALT (PNALT) or minimally elevated ALT. A total of 300 treatment-naive chronic HBV-infected patients with PNALT (ALT ≤ upper limit of normal [ULN, 40 U/ml]) or minimally elevated ALT (1-2×ULN) were retrospectively enrolled. All patients underwent liver biopsy and histological changes were analyzed along with biochemical and HBV markers. Among 300 participants, 177 were HBeAg-positive and 123 HBeAg-negative. Significant histologic abnormalities were found in 42.9% (76/177) and 52.8% (65/123) of HBeAg-positive and HBeAg-negative patients, respectively. Significant fibrosis, which is a marker of prior injury, was more frequently detected than significant necroinflammation (suggesting active liver injury) in both HBeAg-positive and -negative groups, suggesting that liver injury occurred intermittently in our cohort. No significant differences were noticed in the percentage of patients with severe fibrosis between HBeAg-positive and negative phases or between ages 30 and 40 and over 40, suggesting that the fibrosis was possibly carried over from an early phase. Finally, lowering ALT ULN (30 U/L for men, 19 U/L for women) alone was not adequate to increase the sensitivity of ALT detection of liver injury. However, the study was limited to a small sample size of 13 HBeAg-positive patients with ALT in the revised normal range. We detected significant liver pathology in almost 50% of chronic HBV infected patients with PNALT (ALT ≤ 40 U/ml) or minimally elevated ALT. We postulated that small-scale intermittent liver injury was possibly responsible for the discordance between normal serum ALT and significant liver changes in our cohort.


Assuntos
Alanina Transaminase/sangue , Hepatite B Crônica/enzimologia , Fígado/patologia , Adulto , Feminino , Hepatite B Crônica/patologia , Humanos , Masculino
7.
Arch Virol ; 158(5): 1065-70, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23275097

RESUMO

Enoyl-coenzyme A hydratase (ECHS1) is a key enzyme in the metabolism of fatty acids in mitochondria. We previously reported that hepatitis B surface antigen (HBsAg) interacted with ECHS1 in a yeast two-hybrid system. In the current study, we further examined their interaction by using GST pull-down and co-immunoprecipitation assays. The results confirmed that small hepatitis B surface antigen (SHBs) interacted with ECHS1. Furthermore, confocal imaging showed that SHBs and ECHS1 co-localized in HepG2 cells. To clarify the biological function of the interaction, human hepatoma cell lines that transiently and stably expressed SHBs were generated. The expression of SHBs led to a significant decrease in ECHS1 protein levels. ECHS1 protein levels were reduced to 48.44 ± 7.12 % in Huh7 cells transiently expressing SHBs, and to 54.97 ± 3.54 % in HepG2 cells stably expressing SHBs. In conclusion, our findings suggest that SHBs interacts with ECHS1 and regulates ECHS1 protein levels in hepatoma cells.


Assuntos
Enoil-CoA Hidratase/metabolismo , Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B/patogenicidade , Hepatócitos/virologia , Interações Hospedeiro-Patógeno , Mapeamento de Interação de Proteínas , Linhagem Celular , Centrifugação , Humanos , Imunoprecipitação , Microscopia Confocal , Técnicas do Sistema de Duplo-Híbrido
8.
Mol Med Rep ; 7(2): 664-8, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23241821

RESUMO

The aim of the present study was to investigate the resistance of plasmid-mediated AmpC ß-lactamase in Pseudomonas aeruginosa, to detect and identify the AmpC genotype and to provide evidence for antibiotic applications in the clinic. Resistance phenotype in 108 strains of clinically isolated P. aeruginosa was determined by Kirby-Bauer disk test and cefoxitin three dimensional test in AmpC-positive strains. Plasmids were extracted from AmpC-positive strains using the SDS-alkali splitting technique. The depurated plasmid was used to amplify AmpC ß-lactamase genes by PCR. Positive PCR products were sequenced by the Shanghai Sangon Biological Engineering Technology Company. Gene homology of PCR products with other index sample gene sequences was compared. In the present study, 28 AmpC enzyme-positive P. aeruginosa strains among 108 were identified. Multidrug­resistance to antibiotics was observed in positive AmpC P. aeruginosa strains and a new P. aeruginosa strain of plasmid-mediated CMY-7 type AmpC enzyme was identified. In addition, AmpC type ß-lactamases were revealed to be important in the resistance mechanism to antibiotics in P. aeruginosa. This is the first report of CMY-7 plasmid­mediated AmpC enzyme expression in P. aeruginosa.


Assuntos
Proteínas de Bactérias/biossíntese , Plasmídeos/metabolismo , Pseudomonas aeruginosa/metabolismo , beta-Lactamases/biossíntese , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Sequência de Bases , Cefoxitina/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Plasmídeos/genética , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Análise de Sequência de DNA , beta-Lactamases/genética
9.
Zhongguo Zhong Yao Za Zhi ; 37(4): 537-40, 2012 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-22667159

RESUMO

OBJECTIVE: To observe the difference between the combination therapy of alpha-interferon (IFN-alpha) therapy Yixuesheng Capsule and the monotherapy of IFN-alpha in treatment of chronic hepatitis B. METHOD: A total of 288 patients with HBeAg-positive chronic hepatitis B proven by liver biopsy were included in this study. During the individualized therapy, they received hypodermic injection of IFN-alpha 1b, with 5 MU x time(-1) and three times x w(-1). Of them, 125 patients received combination therapy with Yixuesheng Capsule for three months, with 1.0 g/time and three times/d; and 163 patients received only IFN-alpha 1b (the IFN-alpha monotherapy group). After the course of therapy, all patients were followed up for at least 24 months. The intention-to-treat analysis was adopted for statistic analysis. RESULT: The two groups showed no statistical significance by gender, age, liver necroinflammation grading, liver fibrosis staging, serum ALT levels, serum HBV DNA levels and IFN-alpha therapy course. The whole course and the 24-month follow-up visit cover all of 112 patients in the combination treatment group and 141 cases in the IFN-alpha monotherapy group. The response rates of the combination treatment group and the IFN-alpha monotherapy group were 48.0% (60/125) and 35.0% (57/163) (x = 4.980, P = 0.026) at the end of treatment, respectively, 45.6% (57/125) and 33.1% (54/163) (x2 = 4.645, P =0.031) at the end of 12-month-follow-up period, respectively, and 38.4% (48/125) and 32.5% (53/163) (x2 = 1.076, P = 0.300) at the end of 24-month follow-up period, respectively. CONCLUSION: The combination treatment with IFN-alpha and Yixuesheng Capsule shows a slightly better sustained efficacy on HBeAg-positive chronic hepatitis B patients compared with IFN-alpha monotherapy.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Adulto , Cápsulas , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Resultado do Tratamento
11.
Zhonghua Gan Zang Bing Za Zhi ; 19(10): 738-42, 2011 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-22409844

RESUMO

OBJECTIVE: To establish a predictive scoring system which may serve for the prediction of sustained response to conventional interferon-alpha (IFN-alpha) treatment on chronic hepatitis B. METHODS: A total of 474 IFN-alpha treated hepatitis B virus e antigen (HBeAg)-positive patients were enrolled in the present study. The patients' baseline characteristics, such as age, gender, aminotransferases, activity grading (G) of intrahepatic inflammation, score (S) of liver fibrosis, hepatitis B virus (HBV) DNA and genotype were evaluated; therapy duration and response of each patient at the 24th wk after cessation of IFN-alpha treatment were also recorded. A predictive scoring system for a sustained complete response (CR) to IFN-alpha therapy was established based on genetic algorithm. About 10% of the patients were randomly drawn out as the test set. Responses to IFN-alpha therapy were divided into CR, partial response (PR) and non-response (NR). The mixed set of PR and NR was recorded as PR + NR. RESULTS: For the scoring system, the sensitivity and specificity were 78.8% and 80.6%, respectively. CONCLUSION: This SCR scoring system has satisfying prediction efficiency and is easily employed in clinical practice. With this scoring system, practitioners can propose individualized decisions that have an integrated foundation on both evidence-based medicine and personal characteristics.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Adolescente , Adulto , Criança , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto Jovem
12.
World J Gastroenterol ; 16(27): 3465-71, 2010 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-20632453

RESUMO

AIM: To establish a predictive algorithm which may serve for selecting optimal candidates for interferon-alpha (IFN-alpha) treatment. METHODS: A total of 474 IFN-alpha treated hepatitis B virus e antigen (HBeAg)-positive patients were enrolled in the present study. The patients' baseline characteristics, such as age, gender, blood tests, activity grading (G) of intrahepatic inflammation, score (S) of liver fibrosis, hepatitis B virus (HBV) DNA and genotype were evaluated; therapy duration and response of each patient at the 24th wk after cessation of IFN-alpha treatment were also recorded. A predictive algorithm and scoring system for a sustained combined response (CR) to IFN-alpha therapy were established. About 10% of the patients were randomly drawn as the test set. Responses to IFN-alpha therapy were divided into CR, partial response (PR) and non-response (NR). The mixed set of PR and NR was recorded as PR+NR. RESULTS: Stratified by therapy duration, the most significant baseline predictive factors were alanine aminotransferase (ALT), HBV DNA level, aspartate aminotransferase (AST), HBV genotype, S, G, age and gender. According to the established model, the accuracies for sustained CR and PR+NR, respectively, were 86.4% and 93.0% for the training set, 81.5% and 91.0% for the test set. For the scoring system, the sensitivity and specificity were 78.8% and 80.6%, respectively. There were positive correlations between ALT and AST, and G and S, respectively. CONCLUSION: With these models, practitioners may be able to propose individualized decisions that have an integrated foundation on both evidence-based medicine and personal characteristics.


Assuntos
Algoritmos , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Modelos Teóricos , Adolescente , Adulto , Criança , Feminino , Antígenos E da Hepatite B/sangue , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/imunologia , Hepatite B Crônica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Resultado do Tratamento , Adulto Jovem
13.
Zhonghua Gan Zang Bing Za Zhi ; 13(1): 24-6, 2005 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-15670486

RESUMO

OBJECTIVE: To study the causes of poorer antiviral response to neutralizing anti-interferon-alpha antibodies (NA) in male chronic hepatitis B patients treated with recombinant interferon-alpha (rIFN-alpha). METHODS: Two hundred sixty-nine patients (198 males and 71 females) with histologically proven chronic hepatitis B were treated with 5 MU recombinant interferon-alpha 1b (rIFN-alpha 1b) subcutaneously thrice weekly for 6-37 (median 10.0) months. For each patient, serum HBV DNA levels were detected with fluorescent-quantitative PCR, HBeAg with enzymoimmunoassay, and NA with an antiviral neutralizing biological assay during therapy. RESULTS: NA was found in 70 (35.4%) of the 198 males and in 15 (21.1%) of the 71 females during treatment (x2 = 4.894, P = 0.027). At the end of treatment combined-response was achieved in 21 (24.7%) of the 85 NA-positive patients and in 100 (54.3%) of the 184 NA-negative cases (x2 = 20.642). Stratification analysis by NA showed that combined-response rate was significantly lower in males than in females (18.6%, 13/70 vs. 53.3%, 8/15, x2 = 8.024) among NA-positive patients while it was similar in males and in females (50.8%, 65/128, vs. 62.5%, 35/56, x2 = 2.156) among NA-negative patients. In stratification analysis by gender, it was significantly lower in NA-positive patients than in NA-negative ones (18.6%, 13/70 vs. 53.3%, 8/15, x2 = 8.024) among males but there was no significant difference between combined-response rates among females. CONCLUSION: The poorer antiviral response to recombinant interferon-alpha in male chronic hepatitis B patients than in female patients is related to the neutralizing anti-interferon antibodies.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/imunologia , Interferon Tipo I/uso terapêutico , Anticorpos/sangue , Antivirais/imunologia , DNA Viral/sangue , Feminino , Humanos , Interferon Tipo I/imunologia , Masculino , Testes de Neutralização , Proteínas Recombinantes , Fatores Sexuais , Resultado do Tratamento
14.
Di Yi Jun Yi Da Xue Xue Bao ; 24(12): 1398-401, 2004 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-15604068

RESUMO

OBJECTIVE: To investigate the expressions of vascular endothelial growth factor (VEGF) and nm23-H1 gene in breast cancer tissues and their relation to the prognosis in young women. METHODS: The expressions of VEGF and nm23-H1 gene were detected using immunohistochemical method (SP) in the breast cancer tissues of 48 young and 30 postmenopausal women with breast cancer and in breast fibroadenoma tissues of 10 patients for analysis of the association of the expressions with the patients' clinical and pathological characteristics, with also observation of the 5-year survival rate in each patient group. RESULTS: The rates of axillary lymph node metastasis was higher in the young women than in the postmenopausal women, who also had significantly different rates of VEGF and nm23-H1 expressions in the breast cancer tissues (P<0.01, P<0.01 and P<0.05, respectively); between the two breast cancer groups and breast fibroadenoma group, the expressions were also different (P<0.01). In both young and postmenopausal women with breast cancer, patients with axillary lymph node metastasis had significantly higher positivity rate of VEGF expression than those without (P<0.01 and P<0.01), but the reverse was found true in the expression of nm23-H1 gene. VEGF expression was inversely correlated with nm23-H1 expression in young patients (P<0.01), and the 5-year survival rate of patients with nm23-H1 gene expression was higher than that of p53-positive patients (P<0.05). No significant correlation of VEGF and nm23-H1 expressions with the differentiation of the tumor was found (P>0.05). CONCLUSION: The expressions of VEGF and nm23-H1 indicate the angiogenetic activity and invasion of breast cancer, and have a close relation to the prognosis in young women.


Assuntos
Neoplasias da Mama/metabolismo , Núcleosídeo-Difosfato Quinase/biossíntese , Fator A de Crescimento do Endotélio Vascular/biossíntese , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Nucleosídeo NM23 Difosfato Quinases , Núcleosídeo-Difosfato Quinase/genética , Prognóstico , Fator A de Crescimento do Endotélio Vascular/genética
15.
Zhonghua Gan Zang Bing Za Zhi ; 12(10): 582-4, 2004 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-15504285

RESUMO

OBJECTIVE: To investigate the efficacy of interferon-alpha (IFN-alpha) therapy for HBeAg-negative chronic hepatitis B. METHODS: Sixty-five Chinese HBeAg-negative chronic hepatitis B patients were treated with 5 MU recombinant rIFN-alpha 1b subcutaneously thrice weekly for 5 to 24 months, followed by 12 months of treatment-free follow-up; one hundred and eighty-eight Chinese HBeAg-positive patients served as controls. For each patient, serum alanine transaminase (ALT) was measured biochemically and serum HBV DNA level was detected with fluorescent-quantitative PCR, HBeAg with enzymoimmunoassay every 1 to 3 months during therapy and during the follow-up period. HBeAg loss (only for HBeAg-positive cases), HBV DNA undetectable, and ALT normalization: the three together were considered a combined response. RESULTS: Rates of combined response were similar in HBeAg-negative patients (58.5%, 38/65) or HBeAg-positive ones at the end of treatment (weighted chi square test, chi2 = 1.878, P<0.05), but were higher at the end of the follow-up period in the HBeAg-negative cases (75.4%, 49/65) (weighted chi square test, chi2 = 4.796, P<0.05). Furthermore, relapse rates at the end of the follow-up period, were also similar in HBeAg-negative patients (15.8%, 6/38) or HBeAg positive (chi2 = 0.205, P>0.05). Combined response was achieved at a median of 6.0 months (2-16 months) of treatment course in HBeAg-negative patients while at a median of 6.0 months (1-22 months) in HBeAg-positive cases (Z = -0.186, P>0.05, by the Wilcoxon rank sum test). The only factor predictive of combined response, by binary logistic regression analysis, was inflammatory activity in the liver biopsy. Gender, age, baseline ALT level, baseline HBV DNA level, and anti-HBe were not predictive factors. CONCLUSION: Interferon-alpha therapy induces a similar primary and sustained response in HBeAg-negative and in HBeAg-positive chronic hepatitis B patients.


Assuntos
Antígenos E da Hepatite B/sangue , Hepatite B Crônica/terapia , Interferon-alfa/uso terapêutico , Feminino , Seguimentos , Hepatite B Crônica/imunologia , Humanos , Masculino , Resultado do Tratamento
16.
Zhonghua Gan Zang Bing Za Zhi ; 12(4): 205-7, 2004 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-15099466

RESUMO

OBJECTIVE: To investigate the clinical significance of neutralizing anti-interferon-alpha antibodies (NA) in chronic hepatitis B patients treated with recombinant interferon-alpha(rIFN-alpha). METHODS: One hundred and eighty-one patients (128 male and 53 female) with histological proven chronic hepatitis B were treated with 5 MU recombinant interferon-alpha 1b (rIFN-alpha 1b) subcutaneously thrice weekly for 6 to 37 (median 10) months. For each patient, Specific detection of serum HBV DNA level with fluorescent-quantitative PCR, HBeAg with enzymoimmunoassay and NA with an antiviral neutralizing biological assay were performed during therapy. RESULTS: NA was found in 61 (33.7%) of 181 patients. At the end of treatment, complete-response was achieved in 17 (27.9%) of 61 patients with NA and in 54 (45.0%) of 120 patients without NA, respectively (chi2=4.979). For NA positive patients, the complete-response rate was significantly lower in those who had not achieved partial-response prior to or at the same time as NA occurred than in those who did (3.8%, 1/26, vs. 45.7%, 16/35, chi2 = 7.457). Moreover, it was lower in patients who either had 20pg/ml of serum HBV DNA or above or HBV DNA had being reduced by less than 60% recent 3 months, but higher in those who had less than 20pg/ml of HBV DNA and HBV DNA had being reduced by 60% or above (20.0%, 9/45, vs. 56.3%, 9/16, chi2 = 11.009). CONCLUSION: NA may negate the antiviral effects of rIFN-alpha in chronic hepatitis B patients treated with rIFN-alpha, especially if they appear before partial-response or at the occasion at which serum HBV DNA level was not below 20pg/ml or HBV DNA had being reduced by less than 60% recent 3 months.


Assuntos
Anticorpos/sangue , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/imunologia , Interferon-alfa/uso terapêutico , DNA Viral/sangue , Feminino , Hepatite B Crônica/virologia , Humanos , Masculino , Proteínas Recombinantes/uso terapêutico
17.
Di Yi Jun Yi Da Xue Xue Bao ; 23(12): 1319-22, 2003 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-14678902

RESUMO

OBJECTIVE: To investigate the generation of neutralizing anti-interferon-alpha antibodies (NA) in patients with chronic hepatitis B in the course of interferon-alpha treatment, and analyze the factors influencing the production of the antibodies. METHODS: A total of 181 patients with histologically confirmed chronic hepatitis B were enrolled in this study. Recombinant interferon-alpha 1b (rIFN-alpha 1b) was given subcutaneously 3 times a week (5 MU once) in a treatment course lasting for 6 to 37 months (median 10.0 months). In each case, serum NA was detected with antiviral neutralization bioassay, HBeAg with enzyme-linked immunoassay (EIA) and hepatitis B virus DNA with fluorescent quantitative PCR every 1 to 3 months starting from 3 months after the initiation of the treatment. RESULTS: Of the 181 patients, 61 were positive for NA during the treatment course, resulting in an overall NA occurrence rate of 33.7%. The overall incidence rate, as well as the overall prevalence rate, was significantly higher in male than in female patients (39.1% vs 20.8%, (2)=5.622, P=0.018), and no correlations of NA generation was observed with age, pretreatment serum ALT level, serum HBeAg, serum HBV DNA level, liver histological findings or treatment course. Binary logistic regression analysis showed that the only factor in relation with NA production was gender. The prevalence rates of NA varied significantly with the treatment courses ( (2)=98.051, P=0.000). Bivariate correlation analysis showed that the prevalence rate of NA, but not the incidence of NA, was strongly related with the treatment course (r=0.855, P<0.001). CONCLUSIONS: In chronic hepatitis B patients treated with rIFN-alpha 1b, the prevalence rate of NA, instead of the incidence of NA, is significantly related to the treatment course. NA was more likely to develop in male patients to contribute to their poorer antiviral response in comparison with the female patients.


Assuntos
Anticorpos/sangue , Hepatite B Crônica/tratamento farmacológico , Interferon Tipo I/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Hepatite B Crônica/imunologia , Humanos , Interferon Tipo I/uso terapêutico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Testes de Neutralização , Proteínas Recombinantes , Fatores de Tempo
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