Serum Hepatitis B Virus RNA Levels as an Early Predictor of Hepatitis B Envelope Antigen Seroconversion During Treatment With Polymerase Inhibitors
Serum Hepatitis B Virus RNA Levels as an Early Predictor of Hepatitis B Envelope Antigen Seroconversion During Treatment With Polymerase Inhibitors
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DOI：
10.1002/hep.27381
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发表时间：
2015-01-01
期刊：
影响因子：
13.5
通讯作者：
Edelmann, Anke
中科院分区：
文献类型：
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作者：
van Boemmel, Florian;Bartens, Anne;Edelmann, Anke
B型肝炎包膜抗原（HBeAg）血清转换代表慢性B型肝炎病毒（HBV）感染的治疗终点。我们研究了聚合酶抑制剂治疗期间血清HBV RNA水平是否有助于预测HBeAg血清转换。对62例慢性HBV感染者（50例HBeAg阳性）的血清标本进行了HBV RNA检测。患者接受抗病毒治疗的平均持续时间为30 ± 15（范围，4-64）个月。建立了一种新的基于互补DNA末端的实时聚合酶链反应（PCR）快速扩增方法，用于多聚腺苷酸化全长（fl）和截短（tr）HBV RNA的定量分析。在基线、3个月、6个月和随后的时间点测量HBV RNA、HBV DNA和B型肝炎表面抗原（HBsAg）水平以及HBeAg和B型肝炎包膜抗体的存在。15名患者在平均持续时间19 +/- 14后实现HBeAg血清转换（范围，3-56）个月的抗病毒治疗显示平均HBV flRNA和trRNA水平从基线到第3个月的1.0 +/- 1.4显著下降（范围，-1.6-3.4）和2.1 +/- 1.4（范围，0-3.9），至第6个月为1.8 +/- 1.4（范围，0-4.6）和3.1 +/- 1.7（范围，0-5.1）log（10）拷贝/mL，与35例HBeAg阳性但无血清转换的患者相比（第3个月和第6个月P < 0.001）。在HBeAg阴性患者中也观察到类似的HBV RNA水平下降。与HBV DNA、HBsAg、丙氨酸氨基转移酶、HBV基因型、年龄和性别相比，治疗3个月和6个月时HBV RNA水平的下降是HBeAg血清转换的最强预测因子。结论：血清HBV RNA水平可作为预测HBeAg阳性患者聚合酶抑制剂治疗期间血清学应答的新工具。（肝病学2015;61：66-76）
Hepatitis B envelope antigen (HBeAg) seroconversion represents an endpoint of treatment of chronic hepatitis B virus (HBV) infections. We have studied whether levels of serum HBV RNA during polymerase inhibitor treatment might be helpful for predicting HBeAg seroconversion. HBV RNA levels were determined in serial serum samples from 62 patients with chronic HBV infection (50 HBeAg positive). Patients received antiviral treatment for a mean duration of 30 +/- 15 (range, 4-64) months. A new rapid amplification of complimentary DNA-ends-based real-time polymerase chain reaction was established for quantitative analysis of polyadenylated full-length (fl) and truncated (tr) HBV RNA. HBV RNA, HBV DNA, and hepatitis B surface antigen (HBsAg) levels as well as presence of HBeAg and hepatitis B envelope antibody were measured at baseline, month 3, month 6, and subsequent time points. Fifteen patients who achieved HBeAg seroconversion after a mean duration of 19 +/- 14 (range, 3-56) months of antiviral treatment showed a significantly stronger decline in mean HBV flRNA and trRNA levels from baseline to month 3 of 1.0 +/- 1.4 (range, -1.6-3.4) and 2.1 +/- 1.4 (range, 0-3.9) and to month 6 of 1.8 +/- 1.4 (range, 0-4.6) and 3.1 +/- 1.7 (range, 0-5.1) log(10) copies/mL, respectively, in comparison to 35 HBeAg-positive patients without HBeAg seroconversion (P < 0.001 for months 3 and 6). A similar decline in HBV RNA levels was observed in HBeAg-negative patients. The decline of HBV RNA levels at months 3 and 6 of treatment was to be the strongest predictor of HBeAg seroconversion, when compared to levels of HBV DNA, HBsAg, alanine aminotransferase, and HBV genotype, age, and sex. Conclusion: Serum HBV RNA levels may serve as a novel tool for prediction of serological response during polymerase inhibitor treatment in HBeAg-positive patients. (Hepatology 2015;61:66-76)