In the era of antiviral therapy,the main goal of treatment has shifted from the persistent inhibition of hepatitis B virus(HBV)replication to the pursuit of serological clearance of HBs surface antigen(HBsAg).Based on...In the era of antiviral therapy,the main goal of treatment has shifted from the persistent inhibition of hepatitis B virus(HBV)replication to the pursuit of serological clearance of HBs surface antigen(HBsAg).Based on the life cycle of HBV,HBsAg originates from covalently closed circular DNA(cccDNA)and integrated HBV DNA,thus reflecting their transcriptional activity.Complete HBsAg loss may mean elimination or persistent inactivity of the HBV genome including cccDNA and integrated HBV DNA.HBsAg loss improves the recovery of abnormal immune function,which in turn,may further promote the clearance of residual viruses.Combined with functional cure and the great improvement of clinical outcomes,the continuous seroclearance of high-sensitivity quantitative HBsAg may represent the complete cure of chronic hepatitis B(CHB).For many other risk factors besides HBV itself,patients with HBsAg loss still need regular monitoring.In this review,we summarized the evolution of CHB treatment,the origin of serum HBsAg,the pattern of HBsAg seroclearance,and the effect of HBsAg loss on immune function and disease outcomes.In addition,we discuss the significance of high-sensitivity HBsAg detection and its possibility as a surrogate of complete cure.展开更多
Chronic hepatitis B virus(HBV)infection remains a global health burden.Timely and effective antiviral therapy is beneficial for patients with HBV infection.With existing antiviral drugs,including nucleos(t)ide analogs...Chronic hepatitis B virus(HBV)infection remains a global health burden.Timely and effective antiviral therapy is beneficial for patients with HBV infection.With existing antiviral drugs,including nucleos(t)ide analogs and interferon-alfa,patients can achieve viral suppression with improved prognosis.However,the rate of hepatitis B surface antigen loss is low.To achieve a functional cure and even complete cure in chronic hepatitis B patients,new antivirals need to be developed.In this review,we summarized the advantages and disadvantages of existing antiviral drugs and focused on new antivirals including direct-acting antiviral drugs and immunotherapeutic approaches.展开更多
Chronic hepatitis B virus(HBV)infection is a global public health concern.Existing antiviral drugs,including nucleos(t)ide analogs and interferon-α,can suppress HBV replication and improve the prognosis.However,the p...Chronic hepatitis B virus(HBV)infection is a global public health concern.Existing antiviral drugs,including nucleos(t)ide analogs and interferon-α,can suppress HBV replication and improve the prognosis.However,the persistence of covalently closed circular DNA(cccDNA),the integration of HBV-DNA into the host genome,and compromised immune responses impede the successful treatment of hepatitis B.While achieving a functional cure of HBV remains elusive with the current treatment methods,this is the goal of new therapeutic approaches.Therefore,developing novel antiviral drugs is necessary for achieving a functional or complete cure for chronic hepatitis B.In recent years,substantial progress has been made in drug discovery and development for HBV infection.Direct-acting antiviral agents such as entry inhibitors,capsid assembly modulators,subviral particle release inhibitors,cccDNA silencers,and RNA interference molecules have entered clinical trials.In addition,several immunomodulatory agents,including toll-like receptor agonists,therapeutic vaccines,checkpoint inhibitors,and monoclonal antibodies,are also making their way toward clinical use.In this review,we summarize the recent progress and limitations of chronic hepatitis B treatment and discuss perspectives on approaches to achieving functional cure.Although it will take some time for these new antiviral drugs to be widely used in clinical practice,combination therapy may become a preferable treatment option in the future.展开更多
基金supported in part by a grant from the National Major Project for Infectious Diseases Prevention and Treatment (No.2017ZX10302201-004-001,2017ZX10203202-003-003).
文摘In the era of antiviral therapy,the main goal of treatment has shifted from the persistent inhibition of hepatitis B virus(HBV)replication to the pursuit of serological clearance of HBs surface antigen(HBsAg).Based on the life cycle of HBV,HBsAg originates from covalently closed circular DNA(cccDNA)and integrated HBV DNA,thus reflecting their transcriptional activity.Complete HBsAg loss may mean elimination or persistent inactivity of the HBV genome including cccDNA and integrated HBV DNA.HBsAg loss improves the recovery of abnormal immune function,which in turn,may further promote the clearance of residual viruses.Combined with functional cure and the great improvement of clinical outcomes,the continuous seroclearance of high-sensitivity quantitative HBsAg may represent the complete cure of chronic hepatitis B(CHB).For many other risk factors besides HBV itself,patients with HBsAg loss still need regular monitoring.In this review,we summarized the evolution of CHB treatment,the origin of serum HBsAg,the pattern of HBsAg seroclearance,and the effect of HBsAg loss on immune function and disease outcomes.In addition,we discuss the significance of high-sensitivity HBsAg detection and its possibility as a surrogate of complete cure.
基金National Natural Science Foundation of China(Nos.81871668,82070614,and 82100637)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(No.2017BT01S131)。
文摘Chronic hepatitis B virus(HBV)infection remains a global health burden.Timely and effective antiviral therapy is beneficial for patients with HBV infection.With existing antiviral drugs,including nucleos(t)ide analogs and interferon-alfa,patients can achieve viral suppression with improved prognosis.However,the rate of hepatitis B surface antigen loss is low.To achieve a functional cure and even complete cure in chronic hepatitis B patients,new antivirals need to be developed.In this review,we summarized the advantages and disadvantages of existing antiviral drugs and focused on new antivirals including direct-acting antiviral drugs and immunotherapeutic approaches.
基金supported by the National Natural Science Foundation of China Grants 82070641the Clinical Research Award of the First Affiliated Hospital of Xi’an Jiaotong University,China(Nos.XJTU1AF2021CRF-006 and 2022-XKCRC-04)The funding sources were not involved in the study design,writing the manuscript,or decision to submit it for publication.
文摘Chronic hepatitis B virus(HBV)infection is a global public health concern.Existing antiviral drugs,including nucleos(t)ide analogs and interferon-α,can suppress HBV replication and improve the prognosis.However,the persistence of covalently closed circular DNA(cccDNA),the integration of HBV-DNA into the host genome,and compromised immune responses impede the successful treatment of hepatitis B.While achieving a functional cure of HBV remains elusive with the current treatment methods,this is the goal of new therapeutic approaches.Therefore,developing novel antiviral drugs is necessary for achieving a functional or complete cure for chronic hepatitis B.In recent years,substantial progress has been made in drug discovery and development for HBV infection.Direct-acting antiviral agents such as entry inhibitors,capsid assembly modulators,subviral particle release inhibitors,cccDNA silencers,and RNA interference molecules have entered clinical trials.In addition,several immunomodulatory agents,including toll-like receptor agonists,therapeutic vaccines,checkpoint inhibitors,and monoclonal antibodies,are also making their way toward clinical use.In this review,we summarize the recent progress and limitations of chronic hepatitis B treatment and discuss perspectives on approaches to achieving functional cure.Although it will take some time for these new antiviral drugs to be widely used in clinical practice,combination therapy may become a preferable treatment option in the future.
