核苷（酸）类似物（NAs）可有效阻断HBV复制的逆转录和松散环状DNA（rcDNA）合成，进而阻断cccDNA池的补充。近期研究揭示HBV cccDNA的半衰期较短，理论上长期用药应能通过耗竭cccDNA实现慢性乙型肝炎（CHB）的临床治愈。然而，接受NAs治疗的CHB治愈率极低。HBV被公认为DNA病毒，但本室和其他实验室均证实患者血清中存在HBV RNA。我们进而发现，存在于血清中的HBV RNA可能为前基因组RNA（pgRNA），并存在于HBV病毒样颗粒中。我们推测，除丹氏颗粒外，HBV还存在基因组为pgRNA的病毒样颗粒，该病毒样颗粒可能带有与丹氏颗粒一样的包膜蛋白，因此具有潜在感染性。由于NAs类药物不能抑制pgRNA病毒样颗粒的产生及再感染，导致NAs药物难以临床治愈CHB。本课题将进一步探索血清HBV RNA的存在形式、产生机制，并通过临床队列研究揭示其潜在的临床意义。

Nucleot(s)ide analogues (NAs) can block the process of reverse transcription during hepatitis B virus (HBV) replication, and inhibit the formation of HBV rcDNA. Recently, it has been proved that the half-life of HBV covalently closed circular DNA (cccDNA) is not as long as previously described. Since the supplement of cccDNA pool can be blocked by NAs, theoretically, HBV cccDNA can be exhausted and chronic hepatitis B (CHB) could be clinically cured after the prolonged NAs treatment. However, the rate of clinical cure for CHB is extremely low. It has been confirmed the presence of HBV RNA in the serum of HBV infected patients by others and our lab. Our recent data further showed that serum HBV RNA could be HBV pregenomic RNA (pgRNA), which was nucleocapsidated and present in HBV virions. Thus, we speculated that HBV may be consist of both Dane’s particle and HBV pgRNA virions which may have the same potential infectious ability as Dane’s particle. Since NAs only can block the process of reverse transcription, it will not be able to inhibit the production of HBV pgRNA virions. Therefore, we suggest this might be one of the factors contributed to the difficulty in eradicating HBV by NAs treatment. This study will explore the natural characteristics, origin and the potential clinical significance of HBV RNA in serum.