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.
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http://dx.doi.org/10.14218/JCTH.2022.00289 | DOI Listing |
J Chin Med Assoc
December 2024
Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Hepatitis B virus (HBV) infection is regarded as a major health concern worldwide. In patients with chronic HBV infection, exhausted virus-specific CD8+ T cells, resulting from the activation of the programmed cell death protein 1 and programmed death ligand 1 axis, play a key role in the chronicity of infection. Functional cure for HBV, defined as the seroclearance of hepatitis B surface antigen (HBsAg), is viewed as the optimal goal of chronic HBV infection treatment because HBsAg loss is associated with a low risk of hepatocellular carcinoma and a relatively favorable prognosis.
View Article and Find Full Text PDFFront Med (Lausanne)
December 2024
Department of Hepatology, The Third People's Hospital of Taiyuan, Taiyuan, Shanxi Province, China.
Background: Pegylated interferon- (PEG-IFN-α) therapy could decrease hepatitis B surface antigen (HBsAg) and improve long-term prognosis of hepatitis B virus (HBV) infection. However, studies on safety and efficacy of PEG-IFN- for patients with HBV-related cirrhosis are limited.
Methods: This was a single-center study.
Open Forum Infect Dis
December 2024
Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
Background: The kinetics of serum hepatitis B surface antigen (HBsAg) levels during long-term nucleos(t)ide analogue (NA) therapy remains unclear. We delineated the kinetics of HBsAg and analyzed its association with long-term treatment outcomes.
Methods: We enrolled 912 treatment-naïve patients with chronic hepatitis B (CHB) who had received NA therapy for >12 months and analyzed the kinetic patterns through group-based trajectory models (GBTMs).
J Viral Hepat
January 2025
Inserm U1193, Assistance Publique-Hôpitaux de Paris, Hôpital Paul Brousse, Service de Virologie, Université Paris-Saclay, Villejuif, France.
Prognostic factors for the long-term evolution of chronic hepatitis B e antigen (HBeAg)-negative hepatitis B virus (HBV) infection may vary depending on local epidemiology. We aimed to identify these factors in France, where the epidemiology is influenced by diverse immigration. Hepatitis B surface antigen (HBsAg)-positive, HBeAg-negative adults with normal transaminase levels and viral loads < 20,000 IU/mL for 1 year, without viral co-infection or advanced liver disease, were enrolled for a 5-year follow-up.
View Article and Find Full Text PDFGut
December 2024
D-SOLVE consortium, an EU Horizon Europe funded project (No 101057917), Hannover, Germany.
Chronic hepatitis D (CHD) is the most severe form of viral hepatitis, carrying a greater risk of developing cirrhosis and its complications. For decades, pegylated interferon alpha (PegIFN-α) has represented the only therapeutic option, with limited virological response rates and poor tolerability. In 2020, the European Medicines Agency approved bulevirtide (BLV) at 2 mg/day, an entry inhibitor of hepatitis B virus (HBV)/hepatitis delta virus (HDV), which proved to be safe and effective as a monotherapy for up to 144 weeks in clinical trials and real-life studies, including patients with cirrhosis.
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