HBV pregenomic RNA as a predictor of spontaneous HBeAg seroconversion in HBeAg-positive chronic hepatitis B patients BMC Gastroenterology

According to the inclusion criteria, all patients with chronic hepatitis B included in this study were HBeAg positive and in the immune active phase, with HBV DNA levels exceeding 1 × 105 IU/ml and ALT levels were 2 to 10 times the upper limit of normal, and the patient was followed for approximately one and a half years (76 weeks) without antiviral therapy. At the end of follow-up, 18 patients achieved spontaneous HBeAg seroconversion (group A), and 36 patients were randomly selected from other patients without spontaneous HBeAg seroconversion as controls (group B). Serum HBV pgRNA levels significantly decreased in patients with spontaneous HBeAg seroconversion, while no significant decrease was observed in patients in group B, indicating that serum HBV pgRNA may be a new predictor of spontaneous HBeAg seroconversion in HBeAg-positive chronic hepatitis B patients.

As the transcriptional template for all HBV transcripts, intrahepatic covalently closed circular DNA (cccDNA) can generate progeny virion DNA and influence viral protein synthesis. CccDNA is the molecular basis of HBV persistence and is maintained in the nucleus as a stable mini-chromosome (19, 20). Eradication of cccDNA is considered the gold standard for elimination of HBV (21). Therefore, comprehensive monitoring of cccDNA transcriptional activity is of great significance for assessing the efficacy of antiviral treatment and the risk of disease progression (22). However, quantifying cccDNA is impractical in real-life clinical practice due to the invasive nature of liver biopsy, insufficient sample size, subjectivity among different observers, lack of standardized quantification methods, and potential complications of liver biopsy. 21, 23). Therefore, it is of great clinical significance to explore non-invasive, convenient and indirect serum markers that reflect intrahepatic cccDNA levels.

Unlike HBsAg, which is derived not only from cccDNA but also from the integrated HBV genome (24), and HBV DNA can be inhibited by nucleos

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