慢性乙型肝炎患者的抗病毒监测进展和状态：从HBsAg到HBV RNA

StephenW

World J Hepatol. 2018 Sep 27;10(9):603-611. doi: 10.4254/wjh.v10.i9.603.
Progression and status of antiviral monitoring in patients with chronic hepatitis B: From HBsAg to HBV RNA.
Liu YY1, Liang XS2.
Author information

1
    Department of Infectious Diseases, Changhai Hospital of Second Military Medical University, Shanghai 200433, China.
2
    Department of Infectious Diseases, Changhai Hospital of Second Military Medical University, Shanghai 200433, China. [email protected].

Abstract

As alternative indexes of hepatitis B virus (HBV), covalently closed circular DNA (cccDNA) transcriptional activity, hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg), and peripheral blood RNA known as pgRNA, have been advocated as novel serum markers for prediction of prognosis and treatment response in chronic hepatitis B (CHB). Since the availability of commercial quantitative assays of HBsAg in 2011, HBsAg has been widely used for predicting treatment response of patients with CHB. Patients who received interferon therapy have shown a sharper reduction of HBsAg level than those who received nucleoside drug (NAs) therapy. Upon peginterferon treatment, sustained responders have presented a larger reduction of HBsAg level than the non-responders. An absence of HBsAg decline, together with < 2log reduction in HBV DNA at week 12, can serve as a stopping rule in HBsAg-negative patients infected with genotype D HBV. A sharp reduction of HBsAg titer in the NAs therapy is a predictor of HBsAg clearance in long-term treatment. HBcrAg, which consists of three species of related proteins sharing an identical 149 amino acid sequence, including HbcAg, hepatitis B e antigen (HBeAg), and a truncated 22-kDa precore protein, is still detectable in situations where serum HBV DNA levels become undetectable or HBsAg loss is achieved. Therefore, HBcrAg remains a measurable serum marker to correlate with cccDNA in this situation. The decline in HBcrAg has been observed with NAs therapy and the pattern of decline might provide prognostic information on the risk of HBV post-treatment reactivation. Peripheral blood RNA, which is known as pgRNA, directly derives from cccDNA and reflects intrahepatic cccDNA level. Quantitative pgRNA has been suggested to be helpful in CHB management. However, commercial quantitative assays are lacking. Additionally, the use of simultaneous and continuous clearance of HBV RNA and HBV DNA in serum has been suggested to be a safe stopping rule of NAs therapy for patients with CHB. However, clinical studies of large sample sizes are needed to prove the feasibility and significance of using serum HBV RNA as the assessment standard of antiviral therapy in CHB and the safety of the stopping rule in clinics.
KEYWORDS:

Chronic hepatitis B; Hepatitis B core-related antigen; Hepatitis B surface antigen; Interferon; Nucleos(t)ide analogs; Progenome RNA; Response prediction

PMID:
    30310538
PMCID:
    PMC6177569
DOI:
    10.4254/wjh.v10.i9.603

StephenW

世界J Hepatol。 2018年9月27日; 10（9）：603-611。 doi：10.4254 / wjh.v10.i9.603。
慢性乙型肝炎患者的抗病毒监测进展和状态：从HBsAg到HBV RNA。
刘YY1，梁XS2。
作者信息

1
    第二军医大学长海医院感染科，上海200433
2
    第二军医大学长海医院感染科，上海200433 [email protected]。

抽象

作为乙型肝炎病毒（HBV）的替代指标，已提倡共价闭合环状DNA（cccDNA）转录活性，乙型肝炎表面抗原（HBsAg），乙型肝炎核心相关抗原（HBcrAg）和称为pgRNA的外周血RNA。作为预测慢性乙型肝炎（CHB）预后和治疗反应的新型血清标志物。自2011年HBsAg商业化定量分析可用以来，HBsAg已被广泛用于预测CHB患者的治疗反应。接受干扰素治疗的患者HBsAg水平明显低于接受核苷类药物治疗的患者。聚乙二醇干扰素治疗后，持续应答者的HBsAg水平降低幅度大于无应答者。缺乏HBsAg下降，加上第12周HBV DNA <2log减少，可以作为感染基因型D HBV的HBsAg阴性患者的停止规则。 NAs治疗中HBsAg滴度的急剧下降是长期治疗中HBsAg清除率的预测因子。 HBcrAg由三种相关蛋白组成，共有相同的149个氨基酸序列，包括HbcAg，乙型肝炎e抗原（HBeAg）和截短的22-kDa前核心蛋白，在血清HBV DNA水平变得无法检测的情况下仍可检测到或达到HBsAg损失。因此，在这种情况下，HBcrAg仍然是可测量的血清标志物，与cccDNA相关。在NAs治疗中观察到HBcrAg的下降，并且下降的模式可能提供关于HBV治疗后再激活风险的预后信息。外周血RNA，称为pgRNA，直接来源于cccDNA并反映肝内cccDNA水平。已经提出定量pgRNA有助于CHB管理。然而，缺乏商业定量测定。此外，已经建议在血清中同时和连续清除HBV RNA和HBV DNA是CHB患者的NAs治疗的安全停止规则。然而，需要大样本量的临床研究来证明使用血清HBV RNA作为CHB抗病毒治疗评估标准的可行性和重要性以及临床停止治疗的安全性。
关键词：

慢性乙型肝炎;乙型肝炎核心相关抗原;乙型肝炎表面抗原;干扰素;核苷酸（t）ide类似物;前基因组RNA;响应预测

结论：
    30310538
PMCID：
    PMC6177569
DOI：
    10.4254 / wjh.v10.i9.603