Quantitative HBsAg and HBV RNA as markers of latent viral activity in HBeAg-negative patients: a cohort study in Uzbekistan

Chronic hepatitis B (CHB) remains a global health challenge with over 296 million virus carriers and high mortality from complications. In Uzbekistan, HBsAg prevalence reaches 3.7%, highlighting the need for improved diagnostic approaches. Traditional markers (HBV DNA, HBeAg) have limitations, particularly in cases of viral persistence through covalently closed circular DNA (cccDNA) and integrated DNA (iDNA). The study aimed to investigate the relationship between HBV DNA, HBV RNA, and quantitative HBsAg (qH-BsAg) in treatment-naive patients, with emphasis on paradoxical marker dissociation. Methods. This prospective study included 116 adult patients with chronic HBV infection without prior antiviral therapy. Exclusion criteria comprised cirrhosis, hepatocellular carcinoma, and autoimmune diseases. HBV DNA was determined by PCR, HBV RNA by RT-PCR, and qHBsAg by enzyme immunoassay (EIA). Patients were stratified into three groups: DNA+/RNA+ (48 patients – 41.4%), DNA-/ RNA+ (24 patients – 20.7%), and DNA-/RNA- (44 patients – 37.9%). Results. The median qHBsAg levels in DNA+/RNA+ and DNA-/RNA- groups were comparable (4,300 vs 1,840 IU/ mL, p=0.12), but significantly higher in the DNA-/RNA+ group (8,300 IU/mL, p<0.003). In HBeAg-positive patients, a correlation was observed between HBV RNA and qHB-sAg (r=0.592, p<0.001), while no association was found in HBeAg-negative patients. The DNA-/RNA+ group was characterized by elevated ALT levels (34.8 vs 27.8 U/L, p=0.01) and lymphocytosis, indicating immune activation. Conclusion. The paradoxical dissociation of HBV markers in treatment-naive patients demonstrates that the DNA-/ RNA+ phenotype is associated with active cccDNA transcription without DNA replication, accompanied by elevated qHBsAg levels and subclinical hepatitis. Integration of HBV RNA and qHBsAg analysis into clinical practice will improve patient stratification, particularly in regions where HBeAgnegative forms predominate. These findings underscore the necessity for revising diagnostic algorithms to optimize chronic HBV management.