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
Hepatitis B virus(HBV)infection plays an important role in the occurrence and development of hepatocellular carcinoma(HCC),and the rate of HBV infection in liver cancer patients in China is as high as 92.05%.Due to lo...Hepatitis B virus(HBV)infection plays an important role in the occurrence and development of hepatocellular carcinoma(HCC),and the rate of HBV infection in liver cancer patients in China is as high as 92.05%.Due to long-term exposure to chronic antigens from the gut,the liver needs to maintain a certain level of immune tolerance,both to avoid severe inflammation caused by non-pathogenic antigens and to maintain the possibility of rapid and violent responses to infection and tumors.Therefore,HBV infection interacts with the tumor microenvironment(TME)through a highly complex and intertwined signaling pathway,which results in a special TME in HCC.Due to changes in the TME,tumor cells can evade immune surveillance by inhibiting tumor-specific T cell function through cytotoxic T-lymphocy-associated protein-4(CTLA-4)and programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1).Interferons,as a class of immune factors with strong biological activity,can improve the TME of HBV-HCC through various pathways.In recent years,the systematic treatment of HCC has gradually come out of the dilemma.In addition to the continuous emergence of new multi-target anti-vascular tyrosine kinase inhibitor drugs,immune checkpoint inhibitors have opened up a new avenue for the systematic treatment of HCC.At present,immunotherapy based on PD-1/L1 inhibitors has gradually become a new direction of systematic treatment for HCC,and the disease charac-teristics of patients included in global clinical studies are different from those of Chinese patients.Therefore,whether a group of HCC patients with HBV background and poor prognosis in China can also benefit from immunotherapy is an issue of wide concern.This review aims to elucidate the advances of immuno-therapy for HBV related HCC patients with regard to:(1)Immunotherapy based on interferons;(2)Immunotherapy based on PD-1/L1 inhibitors;(3)Immunotherapy based on CTLA4 inhibitors;(4)Adoptive cell transfer;(5)Combination immunotherapy strategy;and(6)Shortcomings of immunotherapy.展开更多
目的鞘脂参与乙型肝炎病毒(HBV)的生命周期并影响干扰素的抗病毒作用。本研究拟通过分析核苷(酸)类似物(NAs)经治慢性乙型肝炎(CHB)患者加用聚乙二醇干扰素α(peg-IFNα)治疗48周血清鞘脂的变化情况,以期筛选出可预测联合治疗48周HBsAg...目的鞘脂参与乙型肝炎病毒(HBV)的生命周期并影响干扰素的抗病毒作用。本研究拟通过分析核苷(酸)类似物(NAs)经治慢性乙型肝炎(CHB)患者加用聚乙二醇干扰素α(peg-IFNα)治疗48周血清鞘脂的变化情况,以期筛选出可预测联合治疗48周HBsAg阴转的鞘脂标志物。方法该单中心、前瞻性队列研究入组了接受核苷(酸)类似物抗病毒治疗1年以上,HBV-DNA检测不到且HBsAg<1500 IU/mL的HBeAg阴性或已发生HBeAg阴转的CHB患者。入组患者加用peg-IFNα-2a或peg-IFNα-2b抗病毒治疗48周。应用超高效液相色谱-串联质谱方法检测基线、12周、24周血清鞘脂水平。主要研究终点是血清鞘脂对48周HBsAg阴转的预测价值。结果53例CHB患者中有48例完成了48周peg-IFNα联合NAs治疗,其中29.2%(14/48)患者实现了HBsAg阴转。基线、12周、24周血清Cerd18:2/22:0、SMd18:2/26:1在HBsAg阴转组及未阴转组之间存在明显差异(P<0.05)。基线HBsAg低水平(OR(95%CI)=0.993(0.987-0.999),P=0.030)、12周血清SMd18:2/26:1高水平(OR(95%CI)=30.366(1.119-823.914),P=0.043)及24周HBsAg定量下降程度(OR(95%CI)=4.696(1.218-18.062),P=0.025)分别是HBsAg阴转的独立预测因素。基线、12周时血清Cerd18:2/22:0分别联合HBsAg定量较之单独相应随访点HBsAg定量对联合治疗48周时HBsAg阴转的预测价值更高(基线AUC:0.895 vs 0.828;12周AUC:0.893 vs 0.861)。结论血清Cerd18:2/22:0联合HBsAg定量可能是早期预测NAs经治CHB患者加用peg-IFNα治疗48周时HBsAg阴转的良好指标。展开更多
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Supported by The National Key Research and Development Program,No.2022YFC2603500 and No.2022YFC2603505Beijing Municipal Health Commission High-Level Public Health Technical Personnel Construction Project,No.Discipline leader-03-26+2 种基金The Digestive Medical Coordinated Development Center of Beijing Hospitals Authority,No.XXZ0302The Capital Health Research and Development of Special Public Health Project,No.2022-1-2172and Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support,No.XMLX 202127.
文摘Hepatitis B virus(HBV)infection plays an important role in the occurrence and development of hepatocellular carcinoma(HCC),and the rate of HBV infection in liver cancer patients in China is as high as 92.05%.Due to long-term exposure to chronic antigens from the gut,the liver needs to maintain a certain level of immune tolerance,both to avoid severe inflammation caused by non-pathogenic antigens and to maintain the possibility of rapid and violent responses to infection and tumors.Therefore,HBV infection interacts with the tumor microenvironment(TME)through a highly complex and intertwined signaling pathway,which results in a special TME in HCC.Due to changes in the TME,tumor cells can evade immune surveillance by inhibiting tumor-specific T cell function through cytotoxic T-lymphocy-associated protein-4(CTLA-4)and programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1).Interferons,as a class of immune factors with strong biological activity,can improve the TME of HBV-HCC through various pathways.In recent years,the systematic treatment of HCC has gradually come out of the dilemma.In addition to the continuous emergence of new multi-target anti-vascular tyrosine kinase inhibitor drugs,immune checkpoint inhibitors have opened up a new avenue for the systematic treatment of HCC.At present,immunotherapy based on PD-1/L1 inhibitors has gradually become a new direction of systematic treatment for HCC,and the disease charac-teristics of patients included in global clinical studies are different from those of Chinese patients.Therefore,whether a group of HCC patients with HBV background and poor prognosis in China can also benefit from immunotherapy is an issue of wide concern.This review aims to elucidate the advances of immuno-therapy for HBV related HCC patients with regard to:(1)Immunotherapy based on interferons;(2)Immunotherapy based on PD-1/L1 inhibitors;(3)Immunotherapy based on CTLA4 inhibitors;(4)Adoptive cell transfer;(5)Combination immunotherapy strategy;and(6)Shortcomings of immunotherapy.
文摘目的鞘脂参与乙型肝炎病毒(HBV)的生命周期并影响干扰素的抗病毒作用。本研究拟通过分析核苷(酸)类似物(NAs)经治慢性乙型肝炎(CHB)患者加用聚乙二醇干扰素α(peg-IFNα)治疗48周血清鞘脂的变化情况,以期筛选出可预测联合治疗48周HBsAg阴转的鞘脂标志物。方法该单中心、前瞻性队列研究入组了接受核苷(酸)类似物抗病毒治疗1年以上,HBV-DNA检测不到且HBsAg<1500 IU/mL的HBeAg阴性或已发生HBeAg阴转的CHB患者。入组患者加用peg-IFNα-2a或peg-IFNα-2b抗病毒治疗48周。应用超高效液相色谱-串联质谱方法检测基线、12周、24周血清鞘脂水平。主要研究终点是血清鞘脂对48周HBsAg阴转的预测价值。结果53例CHB患者中有48例完成了48周peg-IFNα联合NAs治疗,其中29.2%(14/48)患者实现了HBsAg阴转。基线、12周、24周血清Cerd18:2/22:0、SMd18:2/26:1在HBsAg阴转组及未阴转组之间存在明显差异(P<0.05)。基线HBsAg低水平(OR(95%CI)=0.993(0.987-0.999),P=0.030)、12周血清SMd18:2/26:1高水平(OR(95%CI)=30.366(1.119-823.914),P=0.043)及24周HBsAg定量下降程度(OR(95%CI)=4.696(1.218-18.062),P=0.025)分别是HBsAg阴转的独立预测因素。基线、12周时血清Cerd18:2/22:0分别联合HBsAg定量较之单独相应随访点HBsAg定量对联合治疗48周时HBsAg阴转的预测价值更高(基线AUC:0.895 vs 0.828;12周AUC:0.893 vs 0.861)。结论血清Cerd18:2/22:0联合HBsAg定量可能是早期预测NAs经治CHB患者加用peg-IFNα治疗48周时HBsAg阴转的良好指标。
