HBV pgRNA状态预​​测的治疗反应和长期预后

StephenW

January 2, 2020
Treatment Response and Long-Term Prognosis Predicted by HBV pgRNA Status
Infectious Disease Advisor Contributing Writer
Hepatitis B virus (HBV) DNA replication was suppressed and liver inflammation improved in patients with chronic HBV who were treated with long-term nucleos (t) ide analogue (NA) therapy: After 1 year of NA treatment, patients who were HBV pregenomic RNA (pgRNA) -positive required more time to achieve an undetectable HBV DNA load and hepatitis B e antigen (HBeAg) clearance than patients who were HBV pgRNA-negative, according to a study published in the Journal of Viral Hepatitis.

Researchers of this cohort study investigated dynamic changes in HBV DNA and HBeAg status in patients with chronic HBV during NA treatment. The 103 participants who were treatment-naive were categorized according to whether they were HBV pgRNA-negative or HBV pgRNA-positive after NA treatment for 48 weeks. Participants received routine biochemical tests twice a year for 7 years. Over the course of the 7-year study, 21 patients discontinued therapy for various reasons, primarily unwillingness to commit to long-term treatment.


After 48 weeks of treatment, 28 of 58 (48.28%) of HBV DNA undetectable participants were still HBV pgRNA positive, and 5 of 40 (12.5%) HBV DNA detectable participants became HBV pgRNA undetectable. Participants were then divided into HBV pgRNA-negative or HBV pgRNA-positive groups, with 5 patients excluded because of serum sample defects. Of the 98 participants remaining, 63 (64.29%) had detectable HBV pgRNA, and in 35 patients (35.71%), HBV pgRNA was undetectable. More participants in the HBV pgRNA-positive group had also been HBeAg-positive before treatment, and their baseline HBV DNA loads were significantly higher compared with the other group (8.08 ± 1.08 vs 6.64 ± 1.66). Significantly more participants who were HBV pgRNA-negative exhibited HBeAg clearance than those who were HBV pgRNA-positive (19/35 vs 19/63).

After treatment, HBV pgRNA status was significantly different between participants who did achieve HBeAg clearance compared with those who did not (χ² = 78), and the logistic regression model showed an association between HBV pgRNA positivity and an increased risk of not clearing HBeAg (hazard ratio, 6.69; 95% CI, 1.88-23.84). Participants who were categorized as being HBV pgRNA-positive experienced a significantly longer median time to HBeAg clearance than those in the HBV pgRNA-negative group (152 weeks; 95% CI, 93.34 -210 vs 72 weeks; 95% CI, 34.91-109). Participants who were categorized as being HBV pgRNA-positive also required more time to reach undetectable HBV DNA loads (124 weeks; 95% CI, 103.33-144-67 vs 48 weeks; 95% CI, 34.80-61.20).

Study investigators stated, "In conclusion, HBV DNA replication was suppressed, and liver inflammation was improved in CHB patients during oral antiviral therapy. Patients who were HBV pgRNA-positive after NA treatment were less likely to achieve HBeAg clearance and needed more time to achieve HBeAg clearance and an undetectable HBV DNA load than those who were HBV pgRNA-negative after 1 year of NA treatment. "

Reference

Luo H, Tan N, Kang Q, et al. Hepatitis B virus pregenomic RNA status can reveal the long-term prognoses of chronic hepatitis B patients treated with nucleos (t) ide analogues [published online October 31, 2019]. J Viral Hepat . doi: 10.1111 / jvh.13227

StephenW

2020年1月2日
HBV pgRNA状态预​​测的治疗反应和长期预后
传染病顾问撰稿人
经长期核苷酸（t）ide类似物（NA）治疗的慢性HBV患者，乙肝病毒（HBV）DNA复制受到抑制，肝脏炎症得到改善：NA治疗1年后，HBV前基因组RNA患者根据发表在《病毒性肝炎杂志》上的一项研究，与HBV pgRNA阴性的患者相比，（pgRNA）阳性需要更多的时间来实现无法检测到的HBV DNA负荷和乙型肝炎e抗原（HBeAg）清除。

这项队列研究的研究人员调查了NA治疗期间慢性HBV患者的HBV DNA和HBeAg状态的动态变化。根据NA治疗48周后是否为HBV pgRNA阴性或HBV pgRNA阳性，对未接受治疗的103位参与者进行分类。参加者连续7年每年两次接受常规生化测试。在为期7年的研究过程中，有21位患者由于各种原因（主要是不愿接受长期治疗）而终止治疗。


治疗48周后，在58位未检测到的HBV DNA参与者中，有28位（48.28％）仍然是HBV pgRNA阳性，在40位（12.5％）的HBV DNA可检测到的参与者中有5位变为HBV pgRNA不可检测。然后将参与者分为HBV pgRNA阴性或HBV pgRNA阳性，由于血清样品缺陷将5例患者排除在外。在剩余的98位参与者中，有63位（64.29％）具有可检测到的HBV pgRNA，而在35位患者（35.71％）中，HBV pgRNA未被检测到。 HBV pgRNA阳性组中有更多的参与者在治疗前也呈HBeAg阳性，他们的基线HBV DNA载量明显高于另一组（8.08±1.08对6.64±1.66）。与HBV pgRNA阳性的参与者相比，HBV pgRNA阴性的参与者表现出的HBeAg清除率更高（19/35对19/63）。

治疗后，达到HBeAg清除率的参与者与未达到HBeAg清除率的参与者之间的HBV pgRNA状态存在显着差异（χ2 = 78），逻辑回归模型显示HBV pgRNA阳性与不清除HBeAg的风险增加之间存在关联（危险比率为6.69； 95％CI为1.88-23.84）。与HBV pgRNA阴性组相比，被归类为HBV pgRNA阳性的参与者经历的HBeAg清除中值时间明显更长（152周； 95％CI，93.34 -210 vs 72周； 95％CI，34.91-109 ）。被归类为HBV pgRNA阳性的参与者还需要更多时间才能达到无法检测到的HBV DNA负荷（124周； 95％CI，103.33-144-67 vs 48周； 95％CI，34.80-61.20）。

研究人员指出：“结论是，口服抗病毒治疗期间，CHB患者的HBV DNA复制受到抑制，肝脏炎症得到改善。NA治疗后HBV pgRNA阳性的患者获得HBeAg清除的可能性较小，需要更多时间才能达到NA治疗1年后，HBeAg清除率和HBV DNA载量均比HBV pgRNA阴性者高。

参考

罗H，谭N，康Q等。乙型肝炎病毒的基因组RNA状态可以揭示接受核苷酸（t）ide类似物治疗的慢性乙型肝炎患者的长期预后[在线发表于2019年10月31日]。 J病毒性肝炎。 doi：10.1111 / jvh.13227