Hepatitis B surface antigen seroclearance: Immune mechanisms, clinical impact, importance for drug development

Abstract

HBsAg seroclearance occurs rarely in the natural history of chronic hepatitis B (CHB) infection and is associated with improved clinical outcomes. Many factors are associated with HBsAg seroconversion, including immune and viral factors. However, the immune mechanisms associated with HBsAg seroclearance are still difficult to elucidate. HBsAg seroclearance is the ideal aim of HBV treatment. Unfortunately, this goal is rarely achieved with current treatments. Understanding the mechanisms of HBsAg loss appears to be important for the development of curative HBV treatments. While studies from animal models give insights into the potential immune mechanisms and interactions occurring between the immune system and HBsAg, they do not recapitulate all features of CHB in humans and are subject to variability due to their complexity. In this article, we review recent studies on these immune factors, focusing on their influence on CHB progression and HBsAg seroconversion. These data provide new insights for the development of therapeutic approaches to partially restore the anti-HBV immune response. Targeting HBsAg will ideally relieve the immunosuppressive effects on the immune system and help to restore anti-HBV immune responses.

miRNAs as Potential Biomarkers for Viral Hepatitis B and C

“…Therefore, new non-invasive biomarkers are needed to determine, with high precision, the stage of fibrosis to improve prognosis evaluation in patients with Chronic Hepatitis B (CHB) and C (CHC). In patients with CHB, plasma HBsAg is used as a biomarker to stratify the risk of disease progression [ 10 , 11 ]. It has been shown that HBsAg titer was negatively correlated with the stage of the fibrosis in HBeAg-positive patients [ 11 ].…”

“…An HBV infectious particle, which contains HBV genome (a partly double-stranded DNA in relaxed circular form called rcDNA), interacts with the human sodium taurocholate co-transporting polypeptide receptor (hNTCP or SLC10A1), the major HBV receptor described [ 16 ]. This interaction involved the Large Hepatitis B surface antigens (L-HBsAg), one of the three HBsAg exposed at the virion surface ( Figure 1 ) [ 11 ]. Then, HBV rcDNA is release into the nucleus where it can be integrated into the human genome or repaired by different cellular mechanisms into covalently closed circular DNA (cccDNA) [ 17 , 18 ].…”

Benefit of transaminase elevations in establishing functional cure of HBV infection during nap‐based combination therapy

“…12 However, clearance of hepatocytes with integrated HBV DNA may be more dependent on a HBsAgspecific immune response as these hepatocytes appear capable of only producing HBsAg (and SVP) efficiently 27 and are a major source of SVP in HBeAg negative patients. 28,29 SVP constitutes the bulk of circulating HBsAg in chronic infection and appears to be involved in the functional exhaustion of HBV (including HBsAg)-specific B-cell and T-cell immune responses, [30][31][32][33] suggesting that immune targeting of hepatocytes containing integrated HBV DNA may be more efficient with efficient HBsAg clearance. GGT is not as liver-specific as ALT and AST, and its elevation is usually associated with damage to the biliary epithelium or alteration in hepatocyte function, especially in non-viral hepatitis.…”

Immunoglobulins in the treatment of COVID-19 infection: Proceed with caution!

“…As neutralization activity of the anti-viral antibodies was not tested, variability in antibody effectiveness may have contributed to the lack of correlation between anti-viral IgG and clinical outcomes [6]. The use of seroconversion as a biomarker of acquired anti-viral immunity requires determination of the antibody levels indicative of prior infection [7][8][9][10]. Serial antibody testing during the course of COVID-19 infection in 41 patients within this cohort revealed that 71% either seroconverted or demonstrated a four-fold increase in IgG-specific antibody titers, meeting the established criteria for serologic evidence of MERS-CoV infection [6].…”