BACKGROUND Chronic hepatitis B(CHB)patients rarely achieve functional cure with initial pegylated interferon alpha-2b(Peg-IFNα-2b)therapy.Validated tools to guide retreatment candidates are lacking.We hypothesized th...BACKGROUND Chronic hepatitis B(CHB)patients rarely achieve functional cure with initial pegylated interferon alpha-2b(Peg-IFNα-2b)therapy.Validated tools to guide retreatment candidates are lacking.We hypothesized that clinical indicators predict hepatitis B surface antigen(HBsAg)clearance during retreatment.AIM To develop a prediction model for HBsAg clearance in Peg-IFNα-2b retreatment.METHODS In this retrospective cohort study,we enrolled 135 CHB/compensated cirrhosis patients receiving Peg-IFNα-2b retreatment after initial non-clearance at Tianjin University Central Hospital(2017-2025).Predictors were identified through univariate Cox,least absolute shrinkage and selection operator,and multivariate Cox regression.Model performance was assessed via receiver operating characteristic analysis and Harrell’s C-index,with risk stratification by X-tile optimization.RESULTS HBsAg clearance rate was 20.74%(28/135).Independent predictors included:Combination nucleos(t)ide analogue(NA)therapy during initial treatment[hazard ratio(HR)=0.276,95%confidence interval(CI):0.092-0.833],baseline HBsAg at retreatment(HR=0.571,95%CI:0.410-0.795),HBsAg decline after initial treatment(HR=2.050,95%CI:1.108-3.793),and treatment interval(HR=1.013/week,95%CI:1.008-1.018).The retreatment HBsAg clearance prediction score(RHCP-S)demonstrated area under the curve of 0.920(95%CI:0.863-0.946),sensitivity of 92.3%,specificity of 79.3%.Clearance rates differed significantly:RHCP-S challenge group(≤74 points):3.45%,RHCP-S probable group(74-110 points):29.63%,RHCP-S dominant group(≥110 points):80.95%(P<0.001).CONCLUSION The overall HBsAg clearance rate with Peg-IFNα-2b retreatment was 20.74%(28/135).The RHCP-S model identifies optimal retreatment candidates(≥110 points)with 80.95%clearance probability,associated with the absence of combination NA therapy during initial treatment,greater initial HBsAg decline,longer intervals,and lower retreatment HBsAg.展开更多
AIM: To determine the cutoff values and to compare the diagnostic role of alpha-fetoprotein(AFP) and prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ) in chronic hepatitis B(CHB).METHODS: A total of 1255 patients ...AIM: To determine the cutoff values and to compare the diagnostic role of alpha-fetoprotein(AFP) and prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ) in chronic hepatitis B(CHB).METHODS: A total of 1255 patients with CHB, including 157 patients with hepatocellular carcinoma(HCC), 879 with non-cirrhotic CHB and 219 with cirrhosis without HCC, were retrospectively enrolled. The areas under the receiver operating characteristic(AUROC) curves of PIVKA-Ⅱ, AFP and their combination were calculated and compared.RESULTS: The optimal cutoff values for PIVKA-Ⅱ and AFP were 40 m AU/m L and 10 ng/m L, respectively, for the differentiation of HCC from nonmalignant CHB. The sensitivity and specificity were 73.9% and 89.7%, respectively, for PIVKA-Ⅱ and 67.5% and 90.3% for AFP, respectively. The AUROC curves of both PIVKA-Ⅱ and AFP were not significantly different(0.854 vs 0.853, P = 0.965) for the differentiation of HCC from nonmalignant CHB, whereas the AUROC of PIVKA-Ⅱ was significantly better than that of AFP in patients with cirrhosis(0.870 vs 0.812, P = 0.042). When PIVKA-Ⅱ and AFP were combined, the diagnostic power improved significantly compared to either AFP or PIVKA-Ⅱ alone for the differentiation of HCC from nonmalignant CHB(P < 0.05), especially when cirrhosis was present(P < 0.05).CONCLUSION: Serum PIVKA-Ⅱ might be a better tumor marker than AFP, and its combination with AFP may enhance the early detection of HCC in patients with CHB.展开更多
AIM: To assess the effi cacy of peginterferon alpha 2b at doses of 50 μg weekly and 80 μg weekly (based on body weight) plus ribavirin in HCV genotype 2 and genotype 3 chronic hepatitis C patients. METHODS: During t...AIM: To assess the effi cacy of peginterferon alpha 2b at doses of 50 μg weekly and 80 μg weekly (based on body weight) plus ribavirin in HCV genotype 2 and genotype 3 chronic hepatitis C patients. METHODS: During the study period of Jan 2002 to Dec 2003, all patients diagnosed as chronic hepatitis C or HCV related compensated cirrhosis were treated with peginterferon alpha 2b 50 μg S/C weekly (body weight < 60 kg) or 80 μg S/C weekly (body weight > 60 kg) plus ribavirin 800 mg/d for 24 wk. RESULTS: Overall 28 patients, 14 patients in each group (based on body weight) were treated during the period. Out of 28 patients, 75% were genotype 3, 18% were genotype 2 and 7% were genotype 1. The mean dose of peginterferon alpha 2b was 0.91 μg/kg in group 1 and 1.23 μg/kg in group 2 respectively. The end of treatment and sustained virologic response rates were 82% and 78% respectively. Serious adverse effects were seen in 3.5% patients. CONCLUSION: Low dose peginterferon alpha 2b in combination with ribavirin for 24 wk is effective in HCV genotype 2 and 3 chronic hepatitis C patients.展开更多
BACKGROUND The long-term stability of hepatitis B surface antigen(HBsAg)seroclearance following peginterferon alpha(peg-IFN-α)-based therapy has not been extensively studied,leaving the full potential and limitations...BACKGROUND The long-term stability of hepatitis B surface antigen(HBsAg)seroclearance following peginterferon alpha(peg-IFN-α)-based therapy has not been extensively studied,leaving the full potential and limitations of this strategy unclear.AIM To assess HBsAg recurrence after seroclearance achieved by peg-IFN-αregimens.METHODS This prospective,multicenter,observational study was conducted from November 2015 to June 2021 at three Chinese hospitals:The Second Affiliated Hospital of Xi’an Jiaotong University,Ankang Central Hospital,and The Affiliated Hospital of Yan’an University.Participants who achieved HBsAg seroclearance following peg-IFN-α-based treatments were monitored every 4-12 weeks post-treatment for hepatitis B virus(HBV)markers,HBV DNA,and liver function.The primary outcome was HBV recurrence,defined as the reemergence of HBsAg,HBV DNA,or both,at least twice within 4-8 weeks of follow-up.RESULTS In total,121 patients who achieved HBsAg seroclearance were enrolled.After a median follow-up of 84.0(48.0,132.0)weeks,four subjects were lost to follow-up.HBsAg recurrence was detected in 16 patients.The cumulative HBsAg recurrence rate in the intention-to-treat population was 15.2%.Multivariate logistic regression analysis demonstrated that consolidation time<12 weeks[odds ratio(OR)=28.044,95%CI:4.525-173.791]and hepatitis B surface antibody disappearance during follow-up(OR=46.445,95%CI:2.571-838.957)were strong predictors of HBsAg recurrence.HBV DNA positivity and decompensation of liver cirrhosis and hepatocellular carcinoma were not observed.CONCLUSION HBsAg seroclearance following peg-IFN-αtreatment was durable over 84 weeks of follow-up with a cumulative recurrence rate of 15.2%.展开更多
BACKGROUND: Much evidence demonstrates that the genotypes of hepatitis B virus (HBV) present differences in pathogenicity and outcomes owing to differences in genetic structure. This study aimed to investigate the inf...BACKGROUND: Much evidence demonstrates that the genotypes of hepatitis B virus (HBV) present differences in pathogenicity and outcomes owing to differences in genetic structure. This study aimed to investigate the influences of HBV genotypes on the anti-viral therapeutic efficacy of interferon-alpha (IFN-alpha) in chronic hepatitis B patients, and to determine the relationship between HBV genotypes and levels of viral replication or gene variations. METHODS: The chronic hepatitis B patients who were treated with IFN-alpha were selected randomly. Anti-viral therapeutic efficacy was monitored in these patients. The HBV genotypes were detected by PCR microplate hybridization ELISA. The levels of serum HBV-DNA were determined by fluorescence quantitative PCR. HBV gene variation at pre-C and basic core promoter (BCP) regions were assayed by gene chip technology. RESULTS: Genotypes B and C were predominant in 94 chronic hepatitis B patients. A, E and F genotypes were not found in these patients. The HBV-DNA levels of genotype C and mixed genotypes were significantly higher than those of genotype B. The response to IFN-alpha in patients with genotype B was markedly better than in those with genotypes C and D, and the complete response to IFN-alpha was only observed in genotype B. The response to IFN-alpha in patients with mixed genotypes was the least sensitive. The negative transition of HBeAg was correlated with variations in the HBV pre-C and BCP regions in patients with partial or no response to IFN-alpha. The variation rates of HBV pre-C and BCP regions were clearly higher in genotype C than in genotype B. CONCLUSIONS: The results suggest that HBV genotype is correlated with the serum levels of HBV-DNA, HBV gene variations and therapeutic efficacy of IFN-alpha. The regular detection of HBV genotypes in the clinic will be of benefit for disease prognosis and planning of anti-viral therapeutic strategies.展开更多
Objective To explore the predictive value of baseline HBs Ag level and early response for HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment. Methods A tota...Objective To explore the predictive value of baseline HBs Ag level and early response for HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment. Methods A total of 121 patients with HBe Ag-positive chronic hepatitis B who achieved HBs Ag loss were enrolled; all patients were treated with PEG-IFNα-2a 180 μg/week. Serum HBV DNA and serological indicators （HBs Ag, anti-HBs, HBe Ag, and anti-HBe） were determined before and every 3 months during treatment. Results The median treatment time for HBs Ag loss was 84 weeks （7-273 weeks）, and 74.38% （90 cases） of the patients needed extended treatment （〉 48 weeks）. The correlation between baseline HBs Ag levels and the treatment time of HBs Ag loss was significant （B = 14.465, t = 2.342, P = 0.021）. Baseline HBs Ag levels together with the decline range of HBs Ag at 24 weeks significantly correlated with the treatment time of HBs Ag loss （B = 29.862, t = 4.890, P = 0.000 and B = 27.993, t = 27.993, P = 0.005）. Conclusion Baseline HBs Ag levels and extended therapy are critical steps toward HBs Ag loss. Baseline HBs Ag levels together with early response determined the treatment time of HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.展开更多
基金Supported by the Tianjin Health Research Project(Key Project),No.TJWJ2024ZD004Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-034A.
文摘BACKGROUND Chronic hepatitis B(CHB)patients rarely achieve functional cure with initial pegylated interferon alpha-2b(Peg-IFNα-2b)therapy.Validated tools to guide retreatment candidates are lacking.We hypothesized that clinical indicators predict hepatitis B surface antigen(HBsAg)clearance during retreatment.AIM To develop a prediction model for HBsAg clearance in Peg-IFNα-2b retreatment.METHODS In this retrospective cohort study,we enrolled 135 CHB/compensated cirrhosis patients receiving Peg-IFNα-2b retreatment after initial non-clearance at Tianjin University Central Hospital(2017-2025).Predictors were identified through univariate Cox,least absolute shrinkage and selection operator,and multivariate Cox regression.Model performance was assessed via receiver operating characteristic analysis and Harrell’s C-index,with risk stratification by X-tile optimization.RESULTS HBsAg clearance rate was 20.74%(28/135).Independent predictors included:Combination nucleos(t)ide analogue(NA)therapy during initial treatment[hazard ratio(HR)=0.276,95%confidence interval(CI):0.092-0.833],baseline HBsAg at retreatment(HR=0.571,95%CI:0.410-0.795),HBsAg decline after initial treatment(HR=2.050,95%CI:1.108-3.793),and treatment interval(HR=1.013/week,95%CI:1.008-1.018).The retreatment HBsAg clearance prediction score(RHCP-S)demonstrated area under the curve of 0.920(95%CI:0.863-0.946),sensitivity of 92.3%,specificity of 79.3%.Clearance rates differed significantly:RHCP-S challenge group(≤74 points):3.45%,RHCP-S probable group(74-110 points):29.63%,RHCP-S dominant group(≥110 points):80.95%(P<0.001).CONCLUSION The overall HBsAg clearance rate with Peg-IFNα-2b retreatment was 20.74%(28/135).The RHCP-S model identifies optimal retreatment candidates(≥110 points)with 80.95%clearance probability,associated with the absence of combination NA therapy during initial treatment,greater initial HBsAg decline,longer intervals,and lower retreatment HBsAg.
文摘AIM: To determine the cutoff values and to compare the diagnostic role of alpha-fetoprotein(AFP) and prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ) in chronic hepatitis B(CHB).METHODS: A total of 1255 patients with CHB, including 157 patients with hepatocellular carcinoma(HCC), 879 with non-cirrhotic CHB and 219 with cirrhosis without HCC, were retrospectively enrolled. The areas under the receiver operating characteristic(AUROC) curves of PIVKA-Ⅱ, AFP and their combination were calculated and compared.RESULTS: The optimal cutoff values for PIVKA-Ⅱ and AFP were 40 m AU/m L and 10 ng/m L, respectively, for the differentiation of HCC from nonmalignant CHB. The sensitivity and specificity were 73.9% and 89.7%, respectively, for PIVKA-Ⅱ and 67.5% and 90.3% for AFP, respectively. The AUROC curves of both PIVKA-Ⅱ and AFP were not significantly different(0.854 vs 0.853, P = 0.965) for the differentiation of HCC from nonmalignant CHB, whereas the AUROC of PIVKA-Ⅱ was significantly better than that of AFP in patients with cirrhosis(0.870 vs 0.812, P = 0.042). When PIVKA-Ⅱ and AFP were combined, the diagnostic power improved significantly compared to either AFP or PIVKA-Ⅱ alone for the differentiation of HCC from nonmalignant CHB(P < 0.05), especially when cirrhosis was present(P < 0.05).CONCLUSION: Serum PIVKA-Ⅱ might be a better tumor marker than AFP, and its combination with AFP may enhance the early detection of HCC in patients with CHB.
文摘AIM: To assess the effi cacy of peginterferon alpha 2b at doses of 50 μg weekly and 80 μg weekly (based on body weight) plus ribavirin in HCV genotype 2 and genotype 3 chronic hepatitis C patients. METHODS: During the study period of Jan 2002 to Dec 2003, all patients diagnosed as chronic hepatitis C or HCV related compensated cirrhosis were treated with peginterferon alpha 2b 50 μg S/C weekly (body weight < 60 kg) or 80 μg S/C weekly (body weight > 60 kg) plus ribavirin 800 mg/d for 24 wk. RESULTS: Overall 28 patients, 14 patients in each group (based on body weight) were treated during the period. Out of 28 patients, 75% were genotype 3, 18% were genotype 2 and 7% were genotype 1. The mean dose of peginterferon alpha 2b was 0.91 μg/kg in group 1 and 1.23 μg/kg in group 2 respectively. The end of treatment and sustained virologic response rates were 82% and 78% respectively. Serious adverse effects were seen in 3.5% patients. CONCLUSION: Low dose peginterferon alpha 2b in combination with ribavirin for 24 wk is effective in HCV genotype 2 and 3 chronic hepatitis C patients.
基金Supported by National Key Research and Development Program of China,No.2023YFC2308105.
文摘BACKGROUND The long-term stability of hepatitis B surface antigen(HBsAg)seroclearance following peginterferon alpha(peg-IFN-α)-based therapy has not been extensively studied,leaving the full potential and limitations of this strategy unclear.AIM To assess HBsAg recurrence after seroclearance achieved by peg-IFN-αregimens.METHODS This prospective,multicenter,observational study was conducted from November 2015 to June 2021 at three Chinese hospitals:The Second Affiliated Hospital of Xi’an Jiaotong University,Ankang Central Hospital,and The Affiliated Hospital of Yan’an University.Participants who achieved HBsAg seroclearance following peg-IFN-α-based treatments were monitored every 4-12 weeks post-treatment for hepatitis B virus(HBV)markers,HBV DNA,and liver function.The primary outcome was HBV recurrence,defined as the reemergence of HBsAg,HBV DNA,or both,at least twice within 4-8 weeks of follow-up.RESULTS In total,121 patients who achieved HBsAg seroclearance were enrolled.After a median follow-up of 84.0(48.0,132.0)weeks,four subjects were lost to follow-up.HBsAg recurrence was detected in 16 patients.The cumulative HBsAg recurrence rate in the intention-to-treat population was 15.2%.Multivariate logistic regression analysis demonstrated that consolidation time<12 weeks[odds ratio(OR)=28.044,95%CI:4.525-173.791]and hepatitis B surface antibody disappearance during follow-up(OR=46.445,95%CI:2.571-838.957)were strong predictors of HBsAg recurrence.HBV DNA positivity and decompensation of liver cirrhosis and hepatocellular carcinoma were not observed.CONCLUSION HBsAg seroclearance following peg-IFN-αtreatment was durable over 84 weeks of follow-up with a cumulative recurrence rate of 15.2%.
基金This study was supported by a grant from the Scientific and Technology Bureau of Hubei Province Foundation(No.2005AA301C26).
文摘BACKGROUND: Much evidence demonstrates that the genotypes of hepatitis B virus (HBV) present differences in pathogenicity and outcomes owing to differences in genetic structure. This study aimed to investigate the influences of HBV genotypes on the anti-viral therapeutic efficacy of interferon-alpha (IFN-alpha) in chronic hepatitis B patients, and to determine the relationship between HBV genotypes and levels of viral replication or gene variations. METHODS: The chronic hepatitis B patients who were treated with IFN-alpha were selected randomly. Anti-viral therapeutic efficacy was monitored in these patients. The HBV genotypes were detected by PCR microplate hybridization ELISA. The levels of serum HBV-DNA were determined by fluorescence quantitative PCR. HBV gene variation at pre-C and basic core promoter (BCP) regions were assayed by gene chip technology. RESULTS: Genotypes B and C were predominant in 94 chronic hepatitis B patients. A, E and F genotypes were not found in these patients. The HBV-DNA levels of genotype C and mixed genotypes were significantly higher than those of genotype B. The response to IFN-alpha in patients with genotype B was markedly better than in those with genotypes C and D, and the complete response to IFN-alpha was only observed in genotype B. The response to IFN-alpha in patients with mixed genotypes was the least sensitive. The negative transition of HBeAg was correlated with variations in the HBV pre-C and BCP regions in patients with partial or no response to IFN-alpha. The variation rates of HBV pre-C and BCP regions were clearly higher in genotype C than in genotype B. CONCLUSIONS: The results suggest that HBV genotype is correlated with the serum levels of HBV-DNA, HBV gene variations and therapeutic efficacy of IFN-alpha. The regular detection of HBV genotypes in the clinic will be of benefit for disease prognosis and planning of anti-viral therapeutic strategies.
基金supported by Beijing Science and Technology Commission(No.D121100003912001)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding,Support(No.ZY201402)
文摘Objective To explore the predictive value of baseline HBs Ag level and early response for HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment. Methods A total of 121 patients with HBe Ag-positive chronic hepatitis B who achieved HBs Ag loss were enrolled; all patients were treated with PEG-IFNα-2a 180 μg/week. Serum HBV DNA and serological indicators （HBs Ag, anti-HBs, HBe Ag, and anti-HBe） were determined before and every 3 months during treatment. Results The median treatment time for HBs Ag loss was 84 weeks （7-273 weeks）, and 74.38% （90 cases） of the patients needed extended treatment （〉 48 weeks）. The correlation between baseline HBs Ag levels and the treatment time of HBs Ag loss was significant （B = 14.465, t = 2.342, P = 0.021）. Baseline HBs Ag levels together with the decline range of HBs Ag at 24 weeks significantly correlated with the treatment time of HBs Ag loss （B = 29.862, t = 4.890, P = 0.000 and B = 27.993, t = 27.993, P = 0.005）. Conclusion Baseline HBs Ag levels and extended therapy are critical steps toward HBs Ag loss. Baseline HBs Ag levels together with early response determined the treatment time of HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.
