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Discovery and Clinical Application of Serum HBV RNA-like Viral Particles

Dane particles are intact, infectious HBV viral particles carrying a viral genome consisting of relaxed circular DNA (rcDNA) with gaps. It was previously believed that HBV viral particles contained only DNA nucleic acid. In 1996, German scholars discovered the presence of HBV RNA in the serum of chronic HBV-infected individuals, but its source and clinical significance were unclear. Through dedicated research, Professor Lu Fengmin discovered that these RNAs were partially reverse-transcribed or untranscribed pregenomic RNAs (pgRNA) and their splicing variants. Like rcDNA, they could also exist inside the nucleocapsid of mature virus particles. Based on this, these viral particles were named "HBV RNA-like viral particles." Subsequent clinical cohort studies found that the level of serum HBV pgRNA can reflect the quantity and transcriptional activity of covalently closed circular DNA (cccDNA) within hepatocytes of patients with chronic hepatitis B, especially in patients receiving nucleos(t)ide analogue therapy. The continuous disappearance of serum HBV RNA reflects the depletion or transcriptional silence of cccDNA within hepatocytes, termed "functional cure." Combined quantification of HBV RNA and serum HBsAg can greatly predict the risk of drug withdrawal.