400038 重庆,陆军军医大学(第三军医大学)第一附属医院全军感染病研究所,感染病研究重庆市重点实验室
Received:27 September 2021,
Revised:2021-10-09,
Published:30 January 2022
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Zhongwei LIU, Ming LIU, Hongmei GONG, et al. Predictive significance of serum pgRNA in HBeAg clearance for chronic hepatitis B patients with low HBeAg level after pegylated interferon treatment[J]. Journal of Army Medical University, 2022, 44(2): 155-161.
Zhongwei LIU, Ming LIU, Hongmei GONG, et al. Predictive significance of serum pgRNA in HBeAg clearance for chronic hepatitis B patients with low HBeAg level after pegylated interferon treatment[J]. Journal of Army Medical University, 2022, 44(2): 155-161. DOI: 10.16016/j.2097-0927.202109201.
目的
2
评价血清前基因组RNA(pgRNA)对聚乙二醇干扰素-α(polyethylene glycol interferon-alfa
PEG-IFN-α)治疗慢性乙型肝炎(chronic hepatitis B
CHB)患者HBeAg转阴的预测效果。
方法
2
选取2015年11月至2019年7月在本科门诊就诊的25例HBeAg阳性且定量<50 S/CO的CHB患者进行前瞻性研究,采用PEG-IFN-α单药或在原治疗基础上加用PEG-IFN-α进行治疗,计划疗程48~96周。治疗后对患者进行门诊随访,以治疗或随访过程中HBeAg是否转阴将患者分为HBeAg转阴组(HBeAg定量<1.00 COI)和HBeAg未转阴组(HBeAg≥1.00 COI)。分析患者基线特征及治疗过程中各病毒学指标的动态变化规律,应用二元Logistic回归分析及受试者工作特征曲线(ROC)评估各病毒学标志物对HBeAg转阴的预测能力。
结果
2
达治疗终点时共有13例(13/25,52.00%)患者实现HBeAg转阴,基线时两组患者血清pgRNA、HBcrAg水平差异具有统计学意义(
P
<
0.05);基线pgRNA与HBcrAg(
r
=0.575,
P
=0.003)、HBeAg(
r
=0.496,
P
=0.012)具有显著相关性;基线HBcrAg与HBeAg(
r
=0.888,
P
<
0.001)及HBsAg(
r
=0.423,
P
=0.035)具有显著相关性;PEG-IFN-α治疗过程中,25例患者HBeAg整体水平较之基线水平呈下降趋势,不同时间点转阴组HBeAg水平下降幅度均高于未转阴组(
P
<
0.05),基线至12周,pgRNA、HBsAg水平下降明显,其中转
阴组pgRNA下降幅度高于未转阴组(
P
<
0.05),在整个治疗过程中,HBcrAg水平呈现缓慢下降趋势,仅在12~24周时转阴组表现出较大幅度的下降(
P
<
0.05),其他时间点均未见明显变化;ROC曲线分析显示基线pgRNA、HBcrAg是预测HBeAg清除的较好指标,多因素二元Logistic回归分析显示基线pgRNA水平是治疗后HBeAg清除的独立预测因素(
P
<
0.05),AUC为0.763,cut off值为2.42 log
10
copies/mL,灵敏度为69.23%,特异度为53.85%。
结论
2
治疗前血清pgRNA在PEG-IFN-α治疗低HBeAg阳性CHB患者中具有较好的疗效预测价值。
Objective
2
To evaluate the predictive efficacy of serum pregenomic RNA (pgRNA) level in HBeAg clearance for chronic hepatitis B (CHB) patients treated with polyethylene glycol interferon alfa (PEG-IFN-α).
Methods
2
Twenty-five CHB patients with HBeAg positive and quantitative < 50 S/CO treated in our outpatient department from November 2015 to July 2019 were recruited in this prospective study. They were treated with PEG-IFN-α alone or combined with nucleoside and nucleotide analogs (NAs) for 48 to 96 weeks. After treatment
the patients were followed up in the clinic. According to whether HBeAg was cleared during treatment or follow-up
the patients were divided into HBeAg clearance group (HBeAg quantitative < 1.00 COI) and HBeAg non-clearance group (HBeAg ≥1.00 COI). The baseline characteristics and dynamic changes of virological indexes were analyzed for every patient during treatment. The predictive value of virological markers to HBeAg clearance was evaluated by binary logistic regression analysis and receiver operating characteristic (ROC) curve.
Results
2
At the end of treatment
13 patients (13/25
52.00%) achieved HBeAg clearance. There were significant differences in the levels of serum pgRNA and HBcrAg between the 2 groups at baseline (
P
<
0.05); Baseline pgRNA was significantly correlated with HBcrAg (
r
=0.575
P
=0.003) and HBeAg (
r
=0.496
P
=0.012)
and baseline HBcrAg was significantly correlated with HBeAg (
r
=0.888
P
<
0.001) and HBsAg (
r
=0.423
P
=0.035). During the treatment
the overall level of HBeAg in 25 patients showed a downward trend when compared with the baseline level
and the decline of HBeAg level was greater in the HBeAg clearance group than the HBeAg non-clearance group at different time points (
P
<
0.05). From baseline to 12 weeks
the levels of pgRNA and HBsAg were decreased significantly
and its decline of pgRNA was more significant in the HBeAg clearance group than the non-clearance group (
P
<
0.05). During the whole treatment process
the level of HBcrAg was in a slow downward trend
and a significant decrease was observed only at 12 to 24 week in the HBeAg clearance group (
P
<
0.05)
not at other time points. ROC curve analysis showed that baseline pgRNA and HBcrAg were good indicators to predict HBeAg clearance. Multivariate binary logistic regression analysis indicated that baseline pgRNA level was an independent predictor of HBeAg clearance after treatment (
P
<
0.05)
with an AUC of 0.763
cutoff value of 2.42 log
10
copies/mL
a sensitivity of 69.23% and a specificity of 53.85%.
Conclusion
2
Pretreatment serum level of pgRNA shows good predictive value for the efficacy of PEG-IFN-α in CHB patients with low HBeAg level.
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