Clinical significance of serum HBV RNA measurement in chronic hepatitis B patients
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摘要: 在强效核苷及核苷酸类药物(NAs)抗病毒治疗时代,绝大部分慢性乙型肝炎(CHB)患者血清HBV DNA水平低于检测下限,但血清HBV DNA消失仅提示病毒的逆转录过程被有效抑制,并不能真实反映肝细胞内共价闭合环状DNA(ccc DNA)的转录活性状态。另一方面,部分经过长期治疗的患者肝组织ccc DNA接近耗竭或残余静默,但因HBV DNA片段的整合,血清HBs Ag仍持续阳性。如何真实地评判肝细胞内ccc DNA的存在和转录活性,仍是一个亟待解决的问题。血清HBV RNA为来自肝组织内ccc DNA转录体,因未能有效地转换成rc DNA,转而以HBV RNA病毒样颗粒的方式释放进入血液循环。因此在NAs治疗下,血清HBV RNA能够定性反映肝组织内的ccc DNA是否有转录活性。目前多数专家认为,在现有治疗手段下很难达到CHB的"完全治愈"。对此,笔者提出了从"部分治愈"、"准临床治愈"、再到"临床治愈"(或"功能性治愈")的阶梯性提升模式,建议以ccc DNA消失或静默为基础、以HBV RNA持续阴性为依据的"部分治愈"预测NAs停药后复发或病毒学反弹风险,并在此基础上的以血清HB...Abstract: In the era of antiviral therapy with potent nucleos ( t) ide analogues ( NAs) , serum HBV DNA is reduced to a level below the lower limit of detection in most chronic hepatitis B ( CHB) patients, but the loss of serum HBV DNA only indicates that reverse transcription of virus is effectively inhibited and cannot truly reflect the transcriptional activity of covalently closed circular DNA ( ccc DNA) in hepatocytes.In addition, some patients, although with almost depleted or residual, silent ccc DNA in liver tissue, were still positive for serum HBs Ag after long-term treatment due to the integration of HBV DNA fragments. How to truly evaluate the presence and transcriptional activity of ccc DNA in hepatocytes is still a problem that needs to be solved urgently. Serum HBV RNA comes from ccc DNA transcript in liver tissue and is released into blood circulation as virus-like HBV RNA particles, since it is not effectively transformed to rc DNA. Therefore, in patients receiving the treatment with NAs, serum HBV RNA can qualitatively reflect the transcriptional activity of ccc DNA in liver tissue. At present, most scholars think it is hard to achieve " complete cure" of CHB with current therapies. Therefore, we put forward a ladder-like improvement pattern from " partial cure" to " para-functional cure" and " clinical cure" ( or " functional cure") . " Partial cure" based on the elimination or silence of ccc DNA and persistently negative HBV RNA should be used to predict the risk of recurrence or virological rebound after drug withdrawal, and a low serum level of HBs Ag combined with these two criteria should be used as the criteria for " quasi-clinical cure".The clinical significance of serum HBV RNA measurement needs to be addressed in multi-cohort clinical trails and/or improved in the real world studies.
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Key words:
- hepatitis B, chronic /
- hepatitis B virus /
- RNA /
- DNA, circular /
- nucleosides /
- nucleotides
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