Hepatitis B surface antigen(HBsAg)loss is an ideal treatment endpoint for patients with chronic hepatitis B(CHB).We investigated the predictive value of on-treatment HBsAg levels for HBsAg loss in hepatitis B e antige...Hepatitis B surface antigen(HBsAg)loss is an ideal treatment endpoint for patients with chronic hepatitis B(CHB).We investigated the predictive value of on-treatment HBsAg levels for HBsAg loss in hepatitis B e antigen(HBe Ag)-negative CHB patients who received 120-week PEG-IFNα-2a treatment.Serum HBV DNA,HBsAg,and anti-HBs levels were assayed at baseline and every 3 months during the treatment.Of 81 patients,12 achieved HBsAg loss,20 achieved HBsAg\100 IU/mL,and 49 maintained HBs Ag C 100 IU/mL.HBsAg loss rate was only 3.7%at 48 weeks,while it reached to 11.1%and 14.8%after treatment of 96 weeks and 120 weeks.The cutoff HBs Ag levels at 12 weeks predicting HBsAg loss at 96 weeks and 120 weeks of treatment were 400 IU/mL and 750 IU/mL,with AUC 0.725 and 0.722,positive predictive value(PPV)29.41%and 30.56%,and negative predictive value(NPV)93.75%and 97.78%,respectively.The cutoff HBsAg levels at 24 weeks predicting HBsAg loss at 96 weeks and 120 weeks of treatment were 174 IU/m L and 236 IU/mL respectively,with AUC 0.925 and 0.922,PPV 40.0%and 46.15%,and both NPV 100%.The predictive ability of the cutoff HBsAg levels at 24 weeks was better than that at 12 weeks for HBs Ag loss at either 96 or 120 weeks(χ~2=3.880,P=0.049 andχ~2=4.412,P=0.036).These results indicate that extended therapy is critical to HBsAg loss in HBe Ag-negative CHB patients during PEG-IFN treatment,and the HBsAg level at 24 weeks can be used to predict HBsAg loss during tailoring PEG-IFN therapy.展开更多
Background and Aims:Monocyte/macrophage-associat-ed CD163 is an indicator of the severity of liver inflam-mation and cirrhosis,but the difference of soluble CD163(sCD163)levels in chronic hepatitis B(CHB)patients and ...Background and Aims:Monocyte/macrophage-associat-ed CD163 is an indicator of the severity of liver inflam-mation and cirrhosis,but the difference of soluble CD163(sCD163)levels in chronic hepatitis B(CHB)patients and hepatitis B surface antigen(HBsAg)-loss patients is un-clear.Herein,we aimed to compare the sCD163 levels in CHB patients and HBsAg-loss patients with or without an-tiviral treatment.Methods:sCD163 and CD163 expres-sion on monocytes were compared among four groups,healthy subjects,treatment-naïve CHB patients,sponta-neous HBsAg-loss patients,and treatment-related HBsAg-loss patients.The correlation between sCD163 levels and clinical parameters in CHB patients was analyzed.A group of 80 patients with hepatitis B virus(HBV)infection and liver biopsy were recruited.Results:sCD163 levels were higher in the CHB group than in the other three groups.sCD163 levels were higher in treatment-related HBsAg-loss patients than in spontaneous HBsAg-loss patients.sCD163 levels were negatively correlated with hepatitis B e-antigen(HBeAg)and HBsAg levels in HBeAg-positive patients.Liv-er biopsy results further demonstrated that sCD163 levels were elevated in CHB patients with substantial inflamma-tion(A≥2)or fibrosis(F≥2).The sCD163 model was more sensitive in predicting inflammation than other noninvasive models.Its levels were higher in patients with normal ala-nine aminotransferase levels and significant inflammation(A≥2)than in patients with no or mild inflammation.Con-clusions:sCD163 and CD163 expression on monocytes were associated with CHB inflammation and HBsAg loss,and may be used as markers to predict HBV-specific im-mune activation.展开更多
Hepatitis B virus(HBV)reactivation induced by administration of direct-acting antiviral agents(DAAs)to treat hepatitis C virus(HCV)infection has been reported in previous studies,the subsequent clinical outcomes varie...Hepatitis B virus(HBV)reactivation induced by administration of direct-acting antiviral agents(DAAs)to treat hepatitis C virus(HCV)infection has been reported in previous studies,the subsequent clinical outcomes varied from no symptom to liver failure or death,however,the timing of anti-HBV treatment is controversial.We report the clinical HBV reactivation in a 51 years old female fibrotic patient with chronic HBV-HCV infection during the paritaprevir/ritonavir/ombitasvir and dasabuvir(PrOD)therapy.Her baseline HCV RNA,HBV DNA,alanine aminotransferase(ALT),and liver stiffness measurement levels were 5,560,000IU/mL,<15IU/mL,48U/L,and 11.8 kPa,respectively.At 8weeks of PrOD treatment,her HCV RNA,HBV DNA,and ALT levels were<15IU/mL,2,880,000 IU/mL,and 837U/L,respectively,and clinical reactivation was diagnosed.Meanwhile,tenofovir was immediately used for anti-HBV treatment.Fortunately,HBV DNA and ALT were undetectable and normalized after 16weeks of anti-HBV therapy,and unexpectedly,hepatitis B surface antigen loss occurred at 80weeks of anti-HBV treatment.This study may extend our understanding of the timing of anti-HBV therapy to prevent potential HBV reactivation during DAAs treatment in HBVHCV coinfected patients,and proper initiation timing may lead to functional cure of chronic HBV infection.展开更多
Background and aims:The primary goal of chronic hepatitis B(CHB)treatment is to reduce hepatitis B surface antigen(HBsAg).T helper 17(Th17)and regulatory T(Treg)cells are essential for the development of CHB.However,h...Background and aims:The primary goal of chronic hepatitis B(CHB)treatment is to reduce hepatitis B surface antigen(HBsAg).T helper 17(Th17)and regulatory T(Treg)cells are essential for the development of CHB.However,how Th17 and Treg cells contribute to HBsAg loss is still unknown.Therefore,this study aimed to search for the predictive value of Th17 and Treg cells for HBsAg loss in CHB patients with low HBsAg quantification.Methods:The study included 99 hepatitis B e antigen(HBeAg)-negative CHB patients who had completed a year of nucleos(t)ide analogue(NA)monotherapy and had received both NA and pegylated interferon(PEG-IFN)treatment for less than 96 weeks(96 wk).In the cured group,48 patients lost HBsAg within 48 wk,while 51 patients did not(uncured group).Blood samples and clinical data were collected for research.Results:During PEG-IFN and NA combination therapy,the proportion of Th17 cells in the cured group increased significantly,while the proportion of Treg cells in the uncured group increased.From 0 to 24 wk,the proportion of Th17 cells in the cured group was significantly higher than in the uncured group,while the opposite was true for Treg cells.Patients with alanine aminotransferase(ALT)2.5 upper limit of normal(ULN)at 12 wk had a higher proportion of Th17 cells and a lower proportion of Treg cells than those with ALT<2.5 ULN at 12 wk.Additionally,the proportion of Th17 cells is inversely associated with the level of HBsAg,whereas the level of Treg cells is positively related to HBsAg quantification.The clinical cure index,including age,HBsAg quantification,and the proportions of Th17 and Treg cells,had a higher area under the curve(0.957)for predicting HBsAg loss when compared to the proportions of Th17 and Treg cells and HBsAg quantification alone.Conclusions:Combined with quantification of HBsAg,the proportions of Th17 cells and Treg cells at baseline can be used as good predictors of HBsAg loss in patients with low HBsAg quantification treated with NA and PEG-IFN.展开更多
Hepatitis B surface antigen(HBsAg)clearance is considered as functional cure in patients with chronic hepatitis B(CHB).This study aimed to assess the durability of HBsAg clearance achieved by interferon-based therapie...Hepatitis B surface antigen(HBsAg)clearance is considered as functional cure in patients with chronic hepatitis B(CHB).This study aimed to assess the durability of HBsAg clearance achieved by interferon-based therapies in patients with CHB who were originally positive for hepatitis B envelope antigen(HBeAg).In this prospective study,HBeAg-positive CHB patients with confirmed HBsAg loss under interferon-based therapies were enrolled within 12 weeks from end of treatment and followed up for 48 weeks.Virological markers,biochemical indicators,and liver imaging examinations were observed every 3–6 months.Sustained functional cure was analysed as primary outcome.Factor associated with sustained HBsAg loss or reversion was also investigated.The rate of HBsAg loss sustainability was 91.8%(212/231).Patients receiving consolidation treatment for 12–24weeks or≥24 weeks had higher rates of sustained HBsAg negativity than those receiving consolidation treatment for<12 weeks(98.3%and 91.2%vs.86.7%,P=0.068),and the former groups had significantly higher anti-HBs levels than the later(P<0.05).The cumulative incidence of HBsAg reversion and HBV DNA reversion was 8.2%and 3.9%,respectively.Consolidation treatment of≥12 weeks[odd ratio(OR)3.318,95%confidence interval(CI)1.077–10.224,P=0.037)was a predictor of sustained functional cure,and HBeAg-positivity at cessation of treatment(OR 12.271,95%CI 1.076–139.919,P=0.043)was a predictor of HBsAg reversion.Interferon-alpha induced functional cure was durable and a consolidation treatment of≥12–24 weeks was needed after HBsAg loss in HBeAg-positive CHB patients.展开更多
Background and Aims:A functional cure,or hepatitis B virus(HBV)surface antigen(HBsAg)loss,is difficult to achieve in patients with hepatitis B virus e antigen(HBeAg)-positive chronic hepatitis B.The HBV vaccine and gr...Background and Aims:A functional cure,or hepatitis B virus(HBV)surface antigen(HBsAg)loss,is difficult to achieve in patients with hepatitis B virus e antigen(HBeAg)-positive chronic hepatitis B.The HBV vaccine and granulocyte-macrophage colony-stimulating factor(GM-CSF)have been reported to help reduce HBsAg levels and promote HBsAg loss.In this prospective randomized trial,we evaluated HBsAg loss in patients receiving pegylated interferon α2b(PEGIFN-α2b)and tenofovir disoproxil fumarate(TDF),with and without GM-CSF and HBV vaccination.Methods:A total of 287 patients with HBeAg positive chronic hepati-tis B and seroconversion after nucleot(s)ide analog treat-ment were assigned randomly to three treatment groups for 48 weeks,TDF alone(control),PEGIFN-α2b+TDF,and PEGIFN-α2b+TDF+GM-CSF+HBV vaccine.The prima-ry endpoints were the proportions of patients with HBsAg loss and seroconversion at 48 and 72 weeks.Resu/ts:The cumulative HBsAg loss rates in the control,PEGIFN-α2b+TDF,and PEGIFN-α2b+TDF+GM-CSF+HBV vaccine groups at week 48 were 0.0%,28.3%,and 41.1%,respec-tively.The cumulative HBsAg seroconversion rates in these groups at week 48 were 0.0%,21.7%,and 33.9%,respec-tively.Multivariate regression analysis showed that GM-CSF use plus HBV vaccination was significantly associated with HBsAg loss(p=0.017)and seroconversion(p=0.030).Con-clusions:In patients with HBeAg-positive chronic hepatitis B and seroconversion after nucleot(s)ide analog treatment,immunomodulatory/antiviral treatment regimens effective-ly improved HBsAg loss,and the regimen including GM-CSF and HBV vaccination was most effective.展开更多
基金funded in part by the Beijing Hospitals Authority of Hospitals Clinical Medicine Development of Special Funding Support(XMLX 201706)the National Science and Technology Major Project of China(2017ZX10203202-003,2017ZX10201201-001-006,and 2017ZX10201201-002-006)+1 种基金Beijing Science and Technology Commission(D161100002716002)the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority(XXZ0302 and XXT28)。
文摘Hepatitis B surface antigen(HBsAg)loss is an ideal treatment endpoint for patients with chronic hepatitis B(CHB).We investigated the predictive value of on-treatment HBsAg levels for HBsAg loss in hepatitis B e antigen(HBe Ag)-negative CHB patients who received 120-week PEG-IFNα-2a treatment.Serum HBV DNA,HBsAg,and anti-HBs levels were assayed at baseline and every 3 months during the treatment.Of 81 patients,12 achieved HBsAg loss,20 achieved HBsAg\100 IU/mL,and 49 maintained HBs Ag C 100 IU/mL.HBsAg loss rate was only 3.7%at 48 weeks,while it reached to 11.1%and 14.8%after treatment of 96 weeks and 120 weeks.The cutoff HBs Ag levels at 12 weeks predicting HBsAg loss at 96 weeks and 120 weeks of treatment were 400 IU/mL and 750 IU/mL,with AUC 0.725 and 0.722,positive predictive value(PPV)29.41%and 30.56%,and negative predictive value(NPV)93.75%and 97.78%,respectively.The cutoff HBsAg levels at 24 weeks predicting HBsAg loss at 96 weeks and 120 weeks of treatment were 174 IU/m L and 236 IU/mL respectively,with AUC 0.925 and 0.922,PPV 40.0%and 46.15%,and both NPV 100%.The predictive ability of the cutoff HBsAg levels at 24 weeks was better than that at 12 weeks for HBs Ag loss at either 96 or 120 weeks(χ~2=3.880,P=0.049 andχ~2=4.412,P=0.036).These results indicate that extended therapy is critical to HBsAg loss in HBe Ag-negative CHB patients during PEG-IFN treatment,and the HBsAg level at 24 weeks can be used to predict HBsAg loss during tailoring PEG-IFN therapy.
基金the Transgene SA,International Cooperation,a grant from the Shanghai Scientific and Technology Committee(16410711900)National Nature Science grants(81672069 and 81974301).
文摘Background and Aims:Monocyte/macrophage-associat-ed CD163 is an indicator of the severity of liver inflam-mation and cirrhosis,but the difference of soluble CD163(sCD163)levels in chronic hepatitis B(CHB)patients and hepatitis B surface antigen(HBsAg)-loss patients is un-clear.Herein,we aimed to compare the sCD163 levels in CHB patients and HBsAg-loss patients with or without an-tiviral treatment.Methods:sCD163 and CD163 expres-sion on monocytes were compared among four groups,healthy subjects,treatment-naïve CHB patients,sponta-neous HBsAg-loss patients,and treatment-related HBsAg-loss patients.The correlation between sCD163 levels and clinical parameters in CHB patients was analyzed.A group of 80 patients with hepatitis B virus(HBV)infection and liver biopsy were recruited.Results:sCD163 levels were higher in the CHB group than in the other three groups.sCD163 levels were higher in treatment-related HBsAg-loss patients than in spontaneous HBsAg-loss patients.sCD163 levels were negatively correlated with hepatitis B e-antigen(HBeAg)and HBsAg levels in HBeAg-positive patients.Liv-er biopsy results further demonstrated that sCD163 levels were elevated in CHB patients with substantial inflamma-tion(A≥2)or fibrosis(F≥2).The sCD163 model was more sensitive in predicting inflammation than other noninvasive models.Its levels were higher in patients with normal ala-nine aminotransferase levels and significant inflammation(A≥2)than in patients with no or mild inflammation.Con-clusions:sCD163 and CD163 expression on monocytes were associated with CHB inflammation and HBsAg loss,and may be used as markers to predict HBV-specific im-mune activation.
基金This study was supported by The National Natural Science Foundation of China(No.81970517)Talents Project of Health Science and Technology Innovation for Young and Middle-aged Investigators in Henan Province,China(No.2020-OY-04)The Key Scientific Research Project of Henan Higher Education Institutions of China(No.20B320028).
文摘Hepatitis B virus(HBV)reactivation induced by administration of direct-acting antiviral agents(DAAs)to treat hepatitis C virus(HCV)infection has been reported in previous studies,the subsequent clinical outcomes varied from no symptom to liver failure or death,however,the timing of anti-HBV treatment is controversial.We report the clinical HBV reactivation in a 51 years old female fibrotic patient with chronic HBV-HCV infection during the paritaprevir/ritonavir/ombitasvir and dasabuvir(PrOD)therapy.Her baseline HCV RNA,HBV DNA,alanine aminotransferase(ALT),and liver stiffness measurement levels were 5,560,000IU/mL,<15IU/mL,48U/L,and 11.8 kPa,respectively.At 8weeks of PrOD treatment,her HCV RNA,HBV DNA,and ALT levels were<15IU/mL,2,880,000 IU/mL,and 837U/L,respectively,and clinical reactivation was diagnosed.Meanwhile,tenofovir was immediately used for anti-HBV treatment.Fortunately,HBV DNA and ALT were undetectable and normalized after 16weeks of anti-HBV therapy,and unexpectedly,hepatitis B surface antigen loss occurred at 80weeks of anti-HBV treatment.This study may extend our understanding of the timing of anti-HBV therapy to prevent potential HBV reactivation during DAAs treatment in HBVHCV coinfected patients,and proper initiation timing may lead to functional cure of chronic HBV infection.
基金This study was supported by grants from the National Natural Science Foundation of China(82170612,82170364,81901942,81971481)the Medical Science and Technology Foundation of Guangdong Province(A2020264)the Research and Development Planned Project in Key Areas of Guangdong Province(2019B110233002)。
文摘Background and aims:The primary goal of chronic hepatitis B(CHB)treatment is to reduce hepatitis B surface antigen(HBsAg).T helper 17(Th17)and regulatory T(Treg)cells are essential for the development of CHB.However,how Th17 and Treg cells contribute to HBsAg loss is still unknown.Therefore,this study aimed to search for the predictive value of Th17 and Treg cells for HBsAg loss in CHB patients with low HBsAg quantification.Methods:The study included 99 hepatitis B e antigen(HBeAg)-negative CHB patients who had completed a year of nucleos(t)ide analogue(NA)monotherapy and had received both NA and pegylated interferon(PEG-IFN)treatment for less than 96 weeks(96 wk).In the cured group,48 patients lost HBsAg within 48 wk,while 51 patients did not(uncured group).Blood samples and clinical data were collected for research.Results:During PEG-IFN and NA combination therapy,the proportion of Th17 cells in the cured group increased significantly,while the proportion of Treg cells in the uncured group increased.From 0 to 24 wk,the proportion of Th17 cells in the cured group was significantly higher than in the uncured group,while the opposite was true for Treg cells.Patients with alanine aminotransferase(ALT)2.5 upper limit of normal(ULN)at 12 wk had a higher proportion of Th17 cells and a lower proportion of Treg cells than those with ALT<2.5 ULN at 12 wk.Additionally,the proportion of Th17 cells is inversely associated with the level of HBsAg,whereas the level of Treg cells is positively related to HBsAg quantification.The clinical cure index,including age,HBsAg quantification,and the proportions of Th17 and Treg cells,had a higher area under the curve(0.957)for predicting HBsAg loss when compared to the proportions of Th17 and Treg cells and HBsAg quantification alone.Conclusions:Combined with quantification of HBsAg,the proportions of Th17 cells and Treg cells at baseline can be used as good predictors of HBsAg loss in patients with low HBsAg quantification treated with NA and PEG-IFN.
基金funded in part by the Beijing Municipal Science and Technology Commission(No.Z151100004015122)Beijing Municipal Administration of Hospitals’Clinical Medicine Development of special funding support(No.XMLX 201706 and XMLX202127)+3 种基金National Science and Technology Major Project of China(2017ZX10203202-003,2017ZX10201201-001-006,and 2017ZX10201201-002-006)Beijing Science and Technology Commission(No.D161100002716002)Digestive Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals(No.XXZ0302 and XXT28)Special public health project of Capital health development(2021-1G-4061 and 2022-1-2172)。
文摘Hepatitis B surface antigen(HBsAg)clearance is considered as functional cure in patients with chronic hepatitis B(CHB).This study aimed to assess the durability of HBsAg clearance achieved by interferon-based therapies in patients with CHB who were originally positive for hepatitis B envelope antigen(HBeAg).In this prospective study,HBeAg-positive CHB patients with confirmed HBsAg loss under interferon-based therapies were enrolled within 12 weeks from end of treatment and followed up for 48 weeks.Virological markers,biochemical indicators,and liver imaging examinations were observed every 3–6 months.Sustained functional cure was analysed as primary outcome.Factor associated with sustained HBsAg loss or reversion was also investigated.The rate of HBsAg loss sustainability was 91.8%(212/231).Patients receiving consolidation treatment for 12–24weeks or≥24 weeks had higher rates of sustained HBsAg negativity than those receiving consolidation treatment for<12 weeks(98.3%and 91.2%vs.86.7%,P=0.068),and the former groups had significantly higher anti-HBs levels than the later(P<0.05).The cumulative incidence of HBsAg reversion and HBV DNA reversion was 8.2%and 3.9%,respectively.Consolidation treatment of≥12 weeks[odd ratio(OR)3.318,95%confidence interval(CI)1.077–10.224,P=0.037)was a predictor of sustained functional cure,and HBeAg-positivity at cessation of treatment(OR 12.271,95%CI 1.076–139.919,P=0.043)was a predictor of HBsAg reversion.Interferon-alpha induced functional cure was durable and a consolidation treatment of≥12–24 weeks was needed after HBsAg loss in HBeAg-positive CHB patients.
基金Ministry of science and technology of China(2017ZX10202202)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-045)National Key R&D Program of China(2022YFC2304500).
文摘Background and Aims:A functional cure,or hepatitis B virus(HBV)surface antigen(HBsAg)loss,is difficult to achieve in patients with hepatitis B virus e antigen(HBeAg)-positive chronic hepatitis B.The HBV vaccine and granulocyte-macrophage colony-stimulating factor(GM-CSF)have been reported to help reduce HBsAg levels and promote HBsAg loss.In this prospective randomized trial,we evaluated HBsAg loss in patients receiving pegylated interferon α2b(PEGIFN-α2b)and tenofovir disoproxil fumarate(TDF),with and without GM-CSF and HBV vaccination.Methods:A total of 287 patients with HBeAg positive chronic hepati-tis B and seroconversion after nucleot(s)ide analog treat-ment were assigned randomly to three treatment groups for 48 weeks,TDF alone(control),PEGIFN-α2b+TDF,and PEGIFN-α2b+TDF+GM-CSF+HBV vaccine.The prima-ry endpoints were the proportions of patients with HBsAg loss and seroconversion at 48 and 72 weeks.Resu/ts:The cumulative HBsAg loss rates in the control,PEGIFN-α2b+TDF,and PEGIFN-α2b+TDF+GM-CSF+HBV vaccine groups at week 48 were 0.0%,28.3%,and 41.1%,respec-tively.The cumulative HBsAg seroconversion rates in these groups at week 48 were 0.0%,21.7%,and 33.9%,respec-tively.Multivariate regression analysis showed that GM-CSF use plus HBV vaccination was significantly associated with HBsAg loss(p=0.017)and seroconversion(p=0.030).Con-clusions:In patients with HBeAg-positive chronic hepatitis B and seroconversion after nucleot(s)ide analog treatment,immunomodulatory/antiviral treatment regimens effective-ly improved HBsAg loss,and the regimen including GM-CSF and HBV vaccination was most effective.
