Paradoxical HBsAg and anti-HBs coexistence among Chronic HBV Infections: Causes and Consequences

Abstract

Hepatitis B surface antigen (HBsAg) and Hepatitis B surface antibody (anti-HBs) were reported simultaneously among Hepatitis B virus (HBV) infections. HBsAg is a specific indicator of acute or chronic HBV infections, while anti-HBs is a protective antibody reflecting the recovery and immunity of hosts. HBsAg and anti-HBs coexist during seroconversion and then form immune complex, which is rare detected in clinical cases. However, with the promotion of vaccination and the application of various antiviral drugs, along with the rapid development of medical technology, the coexistence of HBsAg and anti-HBs has become more prevalent. Mutations in the viral genomes, immune status and genetic factors of hosts may contribute to the coexistence. Novel HBsAg assays, with higher sensitivity and ability to detect mutations or immune complexes, can also yield HBsAg/anti-HBs coexistence. The discovery of coexistence has shattered the idea of traditional serological patterns and raised questions about the effectiveness of vaccines. Worth noting is that HBsAg/anti-HBs double positivity is strongly associated with progressive liver diseases, especially hepatocellular carcinoma. In conclusion, viral mutations, host factors, and methodology impacts can all lead to the coexistence of HBsAg and anti-HBs. This coexistence is not an indicator of improvement, as an increased risk of adverse clinical outcomes still exists.

Mutations in the HBV PreS/S gene related to hepatocellular carcinoma in Vietnamese chronic HBV-infected patients

“…These differences in rates among studies could not only be explained by the distribution of genotype and by the varieties of subgroups in the study populations (such as the co-existence of HBsAg-AntiHBs status, nucleot(s)ide or immunoglobulin treatment, liver cirrhosis and HCC). Moreover, among our study population, antiHBs that had been tested on 186 cases with clinical symptoms were tested antiHBs and had detected 37 cases (19.9%) with HBsAg-AntiHBs co-exsistence, higher than the rates of 3–5% in other investigation [ 32 , 33 ]. Therefore, it was presumed that CHB patients with varieties of presentations had been included in our study and contributed to the difference in rates of point-mutations compared to other studies.…”

Making safe sense of an anti-sense!

“…Reductions in HBsAg, however, were detected in both HBeAg positive and negative groups, thus the target sequence for this ASO may be present even if HBsAg is derived from integrated HBV DNA/genome, thus having the potential for limiting HCC risk. 4 Interestingly, there was an observed transient appearance of anti-HBs antibody in patients with HBsAg loss, consistent with the potential synthesis of antigen-antibody complex formations; the reduction in HBsAg may lead to free HBs-antibody presence, but this requires further work to decipher the mechanisms underlying this process. 4 Overall sustained reductions in HBV DNA levels (<20 IU/mL) were noted in all participants as NA-treatment was administered following bepirovirsen therapy.…”

“…4 Interestingly, there was an observed transient appearance of anti-HBs antibody in patients with HBsAg loss, consistent with the potential synthesis of antigen-antibody complex formations; the reduction in HBsAg may lead to free HBs-antibody presence, but this requires further work to decipher the mechanisms underlying this process. 4 Overall sustained reductions in HBV DNA levels (<20 IU/mL) were noted in all participants as NA-treatment was administered following bepirovirsen therapy. Interestingly, overall absolute reductions in HBV DNA and HBsAg along with HBcrAg and HBV RNA were greater in HBeAg negative patients, suggesting higher baseline antigenic load may be a poor prognostic indicator, thus, reducing HBV DNA loads may be an important pre-requisite for HBV cure.…”

Oxidative Stress in Chronic Hepatitis B—An Update

“…The pre-S1 mRNA and the pre-S2/S mRNA encode the three proteins of HBsAg, which form the viral envelope [ 62 , 64 ]. PreS1 and preS2 deletions in ground-glass hepatocytes are associated with abnormal retention of mutant large and middle surface proteins in the ER [ 65 ]. Moreover, some naturally occurring mutants of the small HBsAg show a reduced ability to be secreted and accumulate in the ER [ 30 ].…”