Unraveling the Complexity of Atypical Serological Profiles in Chronic Hepatitis B: Insights Into Disease Dynamics and Clinical Implications

Introduction Chronic hepatitis B (CHB) continues to be a significant global public health problem. Conventional serological markers play a pivotal role in diagnosing and prognosticating CHB, but atypical serological profiles deviating from established norms pose challenges. Methods A cohort of 35 CHB patients who did not receive an antiviral treatment with atypical serological markers was followed for five years (2017-2022). Demographics, serological parameters, and changes were documented. Serological parameters and serum viral loads (hepatitis B virus (HBV)-deoxyribonucleic acid (DNA) levels) were assayed at the central laboratory during their routine follow-ups. Three groups of atypical serological markers are defined: hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) positivity; hepatitis B e antigen (HBeAg) and anti-hepatitis B e-antigen (anti-HBe) positivity; and isolated core (anti-hepatitis B core (anti-HBc) immunoglobulin G (IgG)) positivity. Patients with concomitant HBsAg and anti-HBs were also stratified into seroreversion groups. Changes in serological markers and HBV-DNA levels across the study period were documented and evaluated at the end of the study period. Statistical analysis was conducted using the Kruskal-Wallis test and IBM SPSS Statistics software for Windows, Version 23.0 (IBM Corp., Armonk, NY, USA). Results In a cohort of 35 patients with atypical hepatitis B serology, demographic analysis revealed that 51.4% (n=18) were female and 48.6% (n=17) were male, with a mean age of 45.7 years. Educational distribution showed that 45.7% (n=16) completed primary education, 22.8% (n=8) had a high school education, and 31.5% (n=11) held university degrees. Among these patients, 10 displayed the concurrent presence of HBsAg and anti-HBs, with 60% (n=6) being female. Serum HBV-DNA was detectable in all cases. After five years, 60% (n=6) exhibited seroconversion from HBsAg to anti-HBs, particularly notable in females (66.7%). These patients showed lower HBsAg titers and serum HBV-DNA levels (p = 0.048, p = 0.036). A subset of 15 patients demonstrated simultaneous HBeAg and anti-HBe positivity. The HBeAg seropositivity waned over time, with 40% (n=6) and 26.7% (n=4) females and males, respectively, retaining positivity by the fifth year. During this period, serum HBV-DNA levels decreased. The remaining five patients sustained HBeAg and anti-HBe positivity. Among 10 patients solely positive for anti-HBc IgG, three had concurrent HBV-DNA positivity. Strikingly, three patients with negative HBV-DNA developed anti-HBs positivity after five years. Conclusion The complexity of CHB infection demands a comprehensive understanding. Atypical serological profiles suggest distinct disease stages, immune response variations, and viral mutations. This study enhances comprehension of viral replication, immune responses, and disease progression, potentially guiding tailored therapeutic strategies.