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HBs Ag低水平作为"准临床治愈"标准。需要特别强调的是,血清HBV RNA检测的临床意义需要大规模的临床研究进行验证,更需要在未来可能的真实世界的应用中不断完善。
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 （cccDNA） in hepatocytes.In addition,some patients,although with almost depleted or residual,silent cccDNA in liver tissue,were still positive for serum HBsAg after long-term treatment due to the integration of HBV DNA fragments.How to truly evaluate the presence and transcriptional activity of cccD-NA in hepatocytes is still a problem that needs to be solved urgently.Serum HBV RNA comes from cccDNA transcript in liver tissue and is released into blood circulation as virus-like HBV RNA particles,since it is not effectively transformed to rcDNA.Therefore,in patients receiving the treatment with NAs,serum HBV RNA can qualitatively reflect the transcriptional activity of cccDNA 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 cccDNA 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 HBsAg 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.
作者
鲁凤民
窦晓光
张文宏
王福生
LU Fengmin;DOU Xiaoguang;ZHANG Wenhong(Department of Microbiology,School of Basic Medical Sciences,Peking University Health Science Center,Beijing 100191,China)
出处
《临床肝胆病杂志》
CAS
北大核心
2018年第5期934-938,共5页
Journal of Clinical Hepatology
