AIM: To study the differential protein profile in serum of hepatitis B patients.METHODS: Serum samples were obtained from patients with chronic hepatitis B who were receiving peginterferon alfa-2b.The serum samples we...AIM: To study the differential protein profile in serum of hepatitis B patients.METHODS: Serum samples were obtained from patients with chronic hepatitis B who were receiving peginterferon alfa-2b.The serum samples were subjected to albumin depletion and analyzed by two-dimensional gel electrophoresis(2-DE).Differentially expressed protein spots were identified by electrospray ionizationquadrupole time-of-flight mass spectrometry.Alpha2-HS-glycoprotein,complement component C3c and CD5 antigen were further analyzed by an enzymelinked immunosorbent assay and immunonephelometry.RESULTS: Nineteen patients with HBeAg-positive chronic hepatitis B(CHB) were studied.These patients were followed for at least 1 year after treatment and were classified according to their treatment response: responders(n = 9) and non-responders(n = 10).2-DE and MS/MS analysis were performed to compare the serum proteins before initiating peginterferon alfa2b.From the quantitative analysis of the 2-D gel,7 proteins were detected between the two groups at different levels before treatment.Among these potential candidates,serum levels of alpha-2-HS-glycoprotein,complement component C3c and CD5 antigen-like precursor were further analyzed.In the validation phase,23 subjects,9 sustained responders and 14 nonresponders,were recruited.Interestingly,the levels of alpha-2-HS-glycoprotein and complement component C3c were elevated in the serum of the non-responders compared to the responders.CONCLUSION: Serum alpha-2-HS-glycoprotein and complement component C3c may be potential serum biomarkers in predicting the treatment response of peginterferon alfa-2b in patients with CHB prior to treatment.展开更多
AIM: To study the safety and efficacy of pegylated interferon alfa-2b, indigenously developed in India, plus ribavirin in treatment of hepatitis C virus(HCV). METHODS: One-hundred HCV patients were enrolled in an open...AIM: To study the safety and efficacy of pegylated interferon alfa-2b, indigenously developed in India, plus ribavirin in treatment of hepatitis C virus(HCV). METHODS: One-hundred HCV patients were enrolled in an open-label, multicenter trial. Patients were treated with pegylated interferon alfa-2b 1.5 μg/kg per week subcutaneously plus oral ribavirin 800 mg/d for patients with genotypes 2 and 3 for 24 wk. The same dose of peginterferon plus weight-based ribavirin(800 mg/d for ≤ 65 kg; 1000 mg/d for > 65-85 kg; 1200 mg/d for > 85-105 kg; 1400 mg/d for > 105 kg body weight) was administered for 48 wk for patients with genotypes 1 and 4. Serological and biochemical responses of patients were assessed.RESULTS: Eighty-two patients(35 in genotypes 1 and 4 and 47 in 2 and 3), completed the study. In genotype 1, 25.9% of patients achieved rapid virologic response(RVR): while the figures were 74.1% for early virologic response(EVR) and 44.4% for sustained virologic response(SVR). For genotypes 2 and 3, all patients bar one belonged to genotype 3, and of those, 71.4%, 87.5%, and 64.3% achieved RVR, EVR, and SVR, respectively. In genotype 4, 58.8%, 88.2%, and 52.9% of patients achieved RVR, EVR, and SVR, respectively. The majority of patients attained normal levels of alanine aminotransferase by 4-12 wk of therapy. Most patients showed a good tolerance for the treatment, although mild-to-moderate adverse events were exhibited; only two patients discontinued the study medication due to serious adverse events(SAEs). Eleven SAEs were observed in nine patients; however, only four SAEs were related to study medication.CONCLUSION: Peginterferon alfa-2b, which was developed in India, in combination with ribavirin, is a safe and effective drug in the treatment of HCV.展开更多
Background： We aimed to evaluate the usefulness of serum hepatitis B virus core-related antigens （HBcrAg） for predicting hepatitis B e antigen （HBeAg） seroconversion in HBeAg-positive chronic hepatitis B patients...Background： We aimed to evaluate the usefulness of serum hepatitis B virus core-related antigens （HBcrAg） for predicting hepatitis B e antigen （HBeAg） seroconversion in HBeAg-positive chronic hepatitis B patients treated with conventional interferon （IFN） alfh-2b or pegylated IFN. Methods： Fifty-eight patients were enrolled： 29 for the training group and 29 for the validating group. HBcrAg was measured at baseline, week 12, end of the treatment, and 12- and 24-week follow-ups. Sixteen patients in the training group were enrolled in the long-term follow-up （LTFU）, during which time the dynamics of the HBcrAg was monitored. Results： The serum HBcrAg level gradually declined during treatment among the HBeAg seroconversion patients of the training group （from baseline, week 12, end of the treatment, 12-week follow-up to 24-week follow-up were II0,245 kU/ml, 3760 kU/ ml, 7410 kU/ml, 715 kU/ml, 200 kU/ml, respectively）. HBcrAg 〈19,565 kU/ml at week 24, HBcrAg 〈34,225 kU/ml at 12-week follow-up, and HBcrAg decrease 〉0.565 log10 kU/ml from the baseline to the end of treatment （EOT） had negative predictive values （NPVs） of 100% for HBeAg seroconversion at the end of follow-up, whereas the positive predictive values （PPVs） were 30.77%, 26.67%, and 25.00%, respectively. The patients with HBeAg seroconversion at the end of 24-week follow-up remained in seroconversion during the LTFU, during which time their serum HBcrAg levels steadily declined or even became undetectable, ranging from 0 to 2.1 kU/ml. Conclusions： Effective antiviral treatment can decrease HBcrAg levels in the serum. The NPVs of HBcrAg for predicting HBeAg seroconversion at 24-week follow-up was 100%, but the PPVs were not satisfactory （all 〈31%）. The serum HBcrAg levels of the patients with HBeAg seroconversion at the end of the 24-week follow-up steadily declined or even became undetectable during the LTFU.展开更多
The efficacy of interferon (IFN) is limited in about 1/3 of patients with chronic hepatitis B (CHB). We used two-dimensional electrophoresis (2-DE)-based proteomic strategies to identify potential serum markers predic...The efficacy of interferon (IFN) is limited in about 1/3 of patients with chronic hepatitis B (CHB). We used two-dimensional electrophoresis (2-DE)-based proteomic strategies to identify potential serum markers predicting hepatitis B e antigen (HBeAg) seroconversion in these patients during IFN therapy. Two groups of patients were enrolled: training and validation. In the training group, 2-DE experiments and subsequent identification of altered levels of proteins showed that α-2-HS-glycoprotein, leucine-rich α-2-glycoprotein, and haptoglobin were significantly upregulated as compared with baseline levels in the HBeAg seroconversion group, whereas apolipoprotein C-III precursor, leucine-rich α-2-glycoprotein, and α-albumin were downregulated in the non-seroconversion group. For patients with HBeAg seroconversion in the training group, Western blot analyses showed that α-2-HS-glycoprotein levels in 75% of patients were significantly upregulated at the end of the treatment as compared with baseline levels. Subsequent experiments in the validation group showed that α-2-HS-glycoprotein levels were significantly increased at week 4 in 83.33% of patients in the HBeAg seroconversion group. Dynamic changes in the serum level of α-2-HS-glycoprotein may be a potential early marker for predicting HBeAg seroconversion during IFN treatment for CHB.展开更多
目的在PEG-IFNα-2b治疗HBeAg阳性慢性乙型肝炎(CHB)过程中,探讨应用不同HBV DNA检测方法对疗效判断的影响。方法选取2014年9月-2016年1月天津市第二人民医院收治的CHB患者,应用PEG-IFNα-2b治疗24周内,HBV DNA低敏方法检测(最低检测下...目的在PEG-IFNα-2b治疗HBeAg阳性慢性乙型肝炎(CHB)过程中,探讨应用不同HBV DNA检测方法对疗效判断的影响。方法选取2014年9月-2016年1月天津市第二人民医院收治的CHB患者,应用PEG-IFNα-2b治疗24周内,HBV DNA低敏方法检测(最低检测下限500 IU/ml)首次阴转,且36周内低敏检测持续阴性的HBeAg阳性CHB患者83例。36周内采用高敏方法检测(最低检测下限20 IU/ml)持续阴性的患者(阴性组)33例,持续阳性的患者(阳性组)50例。对比2组在12、24和36周时HBeAg、HBsAg下降水平以及HBeAg血清学转换率。正态分布的计量资料2组间比较采用成组t检验;非正态分布的计量资料2组间比较采用Mann-Whitney U检验,计数资料2组间比较采用χ~2检验。结果在HBV DNA低敏检测阴性后的12、24和36周,阴性组HBeAg下降值均明显优于阳性组,差异均有统计学意义[0.32(0.16~0.92)log_(10)COI vs 0.14(0.01~0.30)log_(10)COI,Z=-3.061,P=0.002;0.44(0.19~1.15)log_(10)COI vs 0.16(0.04~0.35)log_(10)COI,Z=-3.043,P=0.002;0.51(0.36~1.21)log_(10)COI vs 0.24(0.10~0.46)log_(10)COI,Z=-3.880,P<0.001]。在HBV DNA低敏检测阴性后的12周,2组HBsAg下降水平差异无统计学意义(P=0.067),但在24和36周阴性组HBsAg下降值均明显高于阳性组,差异均有统计学意义[0.13(-0.02~0.33)log_(10)IU/ml vs 0.08(-0.02~0.16)log_(10)IU/ml,Z=-2.207,P=0.021;0.16(0.03~0.47)log_(10)IU/ml vs 0.03(-0.08~0.20)log_(10)IU/ml,Z=-2.363,P=0.018]。在HBV DNA低敏检测阴性后12周,阴性组HBeAg血清学转换率为30.30%,阳性组为16.00%,2组比较差异无统计学意义(P=0.174),24和36周阴性组HBeAg血清学转换率分别为36.36%和39.39%,明显高于阳性组的16.00%和18.00%,2组比较差异均有统计学意义(χ~2=4.507,P=0.040;χ~2=4.671,P=0.042)。结论在PEG-IFN治疗HBeAg阳性CHB的过程中,为更准确的判断患者的抗病毒疗效,HBV DNA应该采用高度敏感的方法检测。展开更多
基金Supported by The 90th Anniversary of Chulalongkorn University Fund(Ratchadaphiseksomphot Endowment Fund)The Thailand Research Fund,No.RMU5180051+2 种基金The Thailand Research Fund Senior Research Scholarship,No.RTA5380005The Higher Education Research Promotion and National Research University Project of Thailand,Office of the Higher Education Commission,No.HR1163AIntegrated Innovation Academic Center,Chulalongkorn University Centenary Academic Development Project,No.CU56-HR05,The Liver Research Unit,Chulalongkorn University
文摘AIM: To study the differential protein profile in serum of hepatitis B patients.METHODS: Serum samples were obtained from patients with chronic hepatitis B who were receiving peginterferon alfa-2b.The serum samples were subjected to albumin depletion and analyzed by two-dimensional gel electrophoresis(2-DE).Differentially expressed protein spots were identified by electrospray ionizationquadrupole time-of-flight mass spectrometry.Alpha2-HS-glycoprotein,complement component C3c and CD5 antigen were further analyzed by an enzymelinked immunosorbent assay and immunonephelometry.RESULTS: Nineteen patients with HBeAg-positive chronic hepatitis B(CHB) were studied.These patients were followed for at least 1 year after treatment and were classified according to their treatment response: responders(n = 9) and non-responders(n = 10).2-DE and MS/MS analysis were performed to compare the serum proteins before initiating peginterferon alfa2b.From the quantitative analysis of the 2-D gel,7 proteins were detected between the two groups at different levels before treatment.Among these potential candidates,serum levels of alpha-2-HS-glycoprotein,complement component C3c and CD5 antigen-like precursor were further analyzed.In the validation phase,23 subjects,9 sustained responders and 14 nonresponders,were recruited.Interestingly,the levels of alpha-2-HS-glycoprotein and complement component C3c were elevated in the serum of the non-responders compared to the responders.CONCLUSION: Serum alpha-2-HS-glycoprotein and complement component C3c may be potential serum biomarkers in predicting the treatment response of peginterferon alfa-2b in patients with CHB prior to treatment.
基金Supported by Virchow Biotech Private Limited,Hyderabad,India
文摘AIM: To study the safety and efficacy of pegylated interferon alfa-2b, indigenously developed in India, plus ribavirin in treatment of hepatitis C virus(HCV). METHODS: One-hundred HCV patients were enrolled in an open-label, multicenter trial. Patients were treated with pegylated interferon alfa-2b 1.5 μg/kg per week subcutaneously plus oral ribavirin 800 mg/d for patients with genotypes 2 and 3 for 24 wk. The same dose of peginterferon plus weight-based ribavirin(800 mg/d for ≤ 65 kg; 1000 mg/d for > 65-85 kg; 1200 mg/d for > 85-105 kg; 1400 mg/d for > 105 kg body weight) was administered for 48 wk for patients with genotypes 1 and 4. Serological and biochemical responses of patients were assessed.RESULTS: Eighty-two patients(35 in genotypes 1 and 4 and 47 in 2 and 3), completed the study. In genotype 1, 25.9% of patients achieved rapid virologic response(RVR): while the figures were 74.1% for early virologic response(EVR) and 44.4% for sustained virologic response(SVR). For genotypes 2 and 3, all patients bar one belonged to genotype 3, and of those, 71.4%, 87.5%, and 64.3% achieved RVR, EVR, and SVR, respectively. In genotype 4, 58.8%, 88.2%, and 52.9% of patients achieved RVR, EVR, and SVR, respectively. The majority of patients attained normal levels of alanine aminotransferase by 4-12 wk of therapy. Most patients showed a good tolerance for the treatment, although mild-to-moderate adverse events were exhibited; only two patients discontinued the study medication due to serious adverse events(SAEs). Eleven SAEs were observed in nine patients; however, only four SAEs were related to study medication.CONCLUSION: Peginterferon alfa-2b, which was developed in India, in combination with ribavirin, is a safe and effective drug in the treatment of HCV.
文摘Background： We aimed to evaluate the usefulness of serum hepatitis B virus core-related antigens （HBcrAg） for predicting hepatitis B e antigen （HBeAg） seroconversion in HBeAg-positive chronic hepatitis B patients treated with conventional interferon （IFN） alfh-2b or pegylated IFN. Methods： Fifty-eight patients were enrolled： 29 for the training group and 29 for the validating group. HBcrAg was measured at baseline, week 12, end of the treatment, and 12- and 24-week follow-ups. Sixteen patients in the training group were enrolled in the long-term follow-up （LTFU）, during which time the dynamics of the HBcrAg was monitored. Results： The serum HBcrAg level gradually declined during treatment among the HBeAg seroconversion patients of the training group （from baseline, week 12, end of the treatment, 12-week follow-up to 24-week follow-up were II0,245 kU/ml, 3760 kU/ ml, 7410 kU/ml, 715 kU/ml, 200 kU/ml, respectively）. HBcrAg 〈19,565 kU/ml at week 24, HBcrAg 〈34,225 kU/ml at 12-week follow-up, and HBcrAg decrease 〉0.565 log10 kU/ml from the baseline to the end of treatment （EOT） had negative predictive values （NPVs） of 100% for HBeAg seroconversion at the end of follow-up, whereas the positive predictive values （PPVs） were 30.77%, 26.67%, and 25.00%, respectively. The patients with HBeAg seroconversion at the end of 24-week follow-up remained in seroconversion during the LTFU, during which time their serum HBcrAg levels steadily declined or even became undetectable, ranging from 0 to 2.1 kU/ml. Conclusions： Effective antiviral treatment can decrease HBcrAg levels in the serum. The NPVs of HBcrAg for predicting HBeAg seroconversion at 24-week follow-up was 100%, but the PPVs were not satisfactory （all 〈31%）. The serum HBcrAg levels of the patients with HBeAg seroconversion at the end of the 24-week follow-up steadily declined or even became undetectable during the LTFU.
基金supported by the National Basic Research Program of China (Grant Nos. 2005CB522902 and 2007CB512900)the National High Technology Research and Development Program of China (Grant No. 2006AA02A410)+4 种基金the National Natural Science Foundation of China (Grant No. 30901256)the Beijing Natural Science Foundation (Grant No. 7102153)National Science and Technology Major Project for Infectious Diseases Control During the 11th Five-Year Plan Period (Grant Nos. 2008ZX10002-012 and 2008ZX10002-013)Peking University People’s Hospital Research Development Funds (Grant No. RDC 2009-13)Key Clinical Research Program of Ministry of Health of China
文摘The efficacy of interferon (IFN) is limited in about 1/3 of patients with chronic hepatitis B (CHB). We used two-dimensional electrophoresis (2-DE)-based proteomic strategies to identify potential serum markers predicting hepatitis B e antigen (HBeAg) seroconversion in these patients during IFN therapy. Two groups of patients were enrolled: training and validation. In the training group, 2-DE experiments and subsequent identification of altered levels of proteins showed that α-2-HS-glycoprotein, leucine-rich α-2-glycoprotein, and haptoglobin were significantly upregulated as compared with baseline levels in the HBeAg seroconversion group, whereas apolipoprotein C-III precursor, leucine-rich α-2-glycoprotein, and α-albumin were downregulated in the non-seroconversion group. For patients with HBeAg seroconversion in the training group, Western blot analyses showed that α-2-HS-glycoprotein levels in 75% of patients were significantly upregulated at the end of the treatment as compared with baseline levels. Subsequent experiments in the validation group showed that α-2-HS-glycoprotein levels were significantly increased at week 4 in 83.33% of patients in the HBeAg seroconversion group. Dynamic changes in the serum level of α-2-HS-glycoprotein may be a potential early marker for predicting HBeAg seroconversion during IFN treatment for CHB.
文摘目的在PEG-IFNα-2b治疗HBeAg阳性慢性乙型肝炎(CHB)过程中,探讨应用不同HBV DNA检测方法对疗效判断的影响。方法选取2014年9月-2016年1月天津市第二人民医院收治的CHB患者,应用PEG-IFNα-2b治疗24周内,HBV DNA低敏方法检测(最低检测下限500 IU/ml)首次阴转,且36周内低敏检测持续阴性的HBeAg阳性CHB患者83例。36周内采用高敏方法检测(最低检测下限20 IU/ml)持续阴性的患者(阴性组)33例,持续阳性的患者(阳性组)50例。对比2组在12、24和36周时HBeAg、HBsAg下降水平以及HBeAg血清学转换率。正态分布的计量资料2组间比较采用成组t检验;非正态分布的计量资料2组间比较采用Mann-Whitney U检验,计数资料2组间比较采用χ~2检验。结果在HBV DNA低敏检测阴性后的12、24和36周,阴性组HBeAg下降值均明显优于阳性组,差异均有统计学意义[0.32(0.16~0.92)log_(10)COI vs 0.14(0.01~0.30)log_(10)COI,Z=-3.061,P=0.002;0.44(0.19~1.15)log_(10)COI vs 0.16(0.04~0.35)log_(10)COI,Z=-3.043,P=0.002;0.51(0.36~1.21)log_(10)COI vs 0.24(0.10~0.46)log_(10)COI,Z=-3.880,P<0.001]。在HBV DNA低敏检测阴性后的12周,2组HBsAg下降水平差异无统计学意义(P=0.067),但在24和36周阴性组HBsAg下降值均明显高于阳性组,差异均有统计学意义[0.13(-0.02~0.33)log_(10)IU/ml vs 0.08(-0.02~0.16)log_(10)IU/ml,Z=-2.207,P=0.021;0.16(0.03~0.47)log_(10)IU/ml vs 0.03(-0.08~0.20)log_(10)IU/ml,Z=-2.363,P=0.018]。在HBV DNA低敏检测阴性后12周,阴性组HBeAg血清学转换率为30.30%,阳性组为16.00%,2组比较差异无统计学意义(P=0.174),24和36周阴性组HBeAg血清学转换率分别为36.36%和39.39%,明显高于阳性组的16.00%和18.00%,2组比较差异均有统计学意义(χ~2=4.507,P=0.040;χ~2=4.671,P=0.042)。结论在PEG-IFN治疗HBeAg阳性CHB的过程中,为更准确的判断患者的抗病毒疗效,HBV DNA应该采用高度敏感的方法检测。
