聚乙二醇干扰素α-2b治疗慢性乙型肝炎患者血清HBsAg清除率的效果分析

李宽; 宁会彬; 靳慧鸣; 彭真; 尚佳

doi:10.3969/j.issn.1001-5256.2023.08.009

聚乙二醇干扰素α-2b治疗慢性乙型肝炎患者血清HBsAg清除率的效果分析

DOI: 10.3969/j.issn.1001-5256.2023.08.009

河南省人民医院感染科，郑州 450003

基金项目:

中国降低乙肝患者肝癌发生率研究(绿洲)工程项目 (LZGC2022-03)

利益冲突声明：本文不存在任何利益冲突。

作者贡献说明：李宽负责撰稿和收集数据；靳慧明负责分析数据；宁会彬、彭真负责收集数据；尚佳负责指导写作和最终定稿。

详细信息

通信作者:
尚佳，shangjia666@126.com (ORCID：0000-0001-9197-8773)

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出版历程
- 收稿日期: 2022-11-29
- 录用日期: 2023-02-01
- 出版日期: 2023-08-20

Effect of pegylated interferon α-2b on serum HBsAg clearance rate in treatment of patients with chronic hepatitis B

Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou 450003, China

Research funding:

China Research on Reducing the Incidence of Liver Cancer in Hepatitis B Patients (Oasis) Project (LZGC2022-03)

More Information

Corresponding author: SHANG Jia, shangjia666@126.com (ORCID: 0000-0001-9197-8773)

摘要

摘要: 目的真实世界中评价聚乙二醇干扰素α-2b(PEG-IFNα-2b)在治疗慢性乙型肝炎(CHB)中清除HBsAg的效果。方法回顾性纳入2017年6月—2021年1月就诊于河南省人民医院感染科的411例CHB患者，所有患者均应用PEG-IFNα-2b治疗。收集患者性别、年龄、抗病毒治疗方案、基线HBsAg水平、治疗后HBsAg水平，观察分析24、48及96周HBsAg清除率。在不同HBsAg基线水平(＜500 IU/mL、500~1 500 IU/mL、1 501~5 000 IU/mL)及不同既往治疗情况和治疗方案后应用PEG-IFNα-2b，比较各随访节点的HBsAg清除率。计量资料两组间比较采用成组t检验，计数资料组间比较采用χ²检验和趋势性χ²检验。结果完成24周治疗患者HBsAg清除率9.9%(26/263)。完成48周治疗患者HBsAg清除率19.7%(25/127)。完成96周治疗患者HBsAg清除率41.7%(30/72)。不同基线HBsAg水平患者治疗24、48及96周时HBsAg清除率比较差异均有统计学意义(χ²值分别为52.265、32.764、30.918，P值均＜0.01)，随着治疗时间延长，HBsAg清除率逐渐升高，并且这种趋势有统计学意义(趋势χ²值分别为44.517、29.147、22.260，P值均＜0.01)。随访24、48及96周时，HBsAg 500~1 500 IU/mL组和1 501~5000 IU/mL组的HBsAg清除率较HBsAg＜500 IU/mL组均明显下降(P值均＜0.001)。在治疗24、48及96周时，治疗情况(初治或经治)及治疗方案(单用或联合)患者相比较，仅初治与经治组在男女比例上存在差异(χ²=5.029，P=0.025)；初治或经治组间、单用或联合治疗组间HBsAg清除率比较差异均无统计学意义(P值均＞0.05)。结论 PEG-IFNα-2b在治疗CHB中对清除HBsAg有良好的效果，并且基线HBsAg水平越低，HBsAg清除率越高，随着治疗时间的延长，HBsAg清除率呈上升趋势。基线HBsAg 500 IU/mL可作为优势人群的分界点。
- 聚乙二醇干扰素α-2b /
- 乙型肝炎, 慢性 /
- 乙型肝炎表面抗原
Abstract: Objective To investigate the effect of pegylated interferon α-2b (PEG-IFNα-2b) on HBsAg clearance in the treatment of chronic hepatitis B (CHB) in a real-world setting. Methods A retrospective analysis was performed for 411 CHB patients who attended Department of Infectious Diseases, Henan Provincial People's Hospital, from June 2017 to January 2021, and all these patients were treated with PEG-IFNα-2b. Related clinical data were collected, including sex, age, antiviral treatment regimen, baseline HBsAg level, and post-treatment HBsAg level, and HBsAg clearance rate was observed at 24, 48, and 96 weeks. HBsAg clearance rate at different time points of follow-up was compared between the patients with different baseline HBsAg levels (< 500 IU/mL, 500-1 500 IU/mL, and 1 501-5 000 IU/mL) or with the use of PEG-IFNα-2b after different previous treatment conditions and regimens. The independent-samples t test was used for comparison of continuous data between two groups, and the chi-square test and the trend chi-square test were used for comparison of categorical data between groups. Results The HBsAg clearance rate was 9.9% (26/263) in the patients who completed 24 weeks of treatment, 19.7% (25/127) in the patients who completed 48 weeks of treatment, and 41.7% (30/72) in the patients who completed 96 weeks of treatment. There was a significant difference in HBsAg clearance rate between the patients with different baseline HBsAg levels at 24, 48, and 96 weeks of treatment (χ²=52.265, 32.764, and 30.918, all P < 0.01), and HBsAg clearance rate gradually increased over the time of treatment (χ_trend²=44.517, 29.147, and 22.260, all P < 0.01). Compared with the HBsAg < 500 IU/mL group, the 500-1 500 IU/mL group and the 1 501-5 000 IU/mL group had a significant reduction in HBsAg clearance rate at 24, 48, and 96 weeks of follow-up (all P < 0.001). As for the comparison of the patients with different treatment conditions (previously untreated or treatment-experienced) and treatment regimens (monotherapy or combined therapy) at 24, 48, and 96 weeks of treatment, there was a significant difference in fame/female ration between the previously untreated group and the treatment-experienced group (χ²=5.029, P=0.025), and there was no significant difference in HBsAg clearance rate between the previously untreated group and the treatment-experienced group and between the monotherapy group and the combined therapy group (all P > 0.05). Conclusion PEG-IFNα-2b has a marked effect on HBsAg clearance in the treatment of CHB, and patients with a lower baseline HBsAg level tend to have a higher HBsAg clearance rate. HBsAg clearance rate tends to increase over the time of treatment. A baseline HBsAg level of 500 IU/mL can be used as the cut-off point to identify the dominant population.
- Pegylated Interferon α-2b /
- Hepatitis B, Chronic /
- Hepatitis B Surface Antigens

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表 1 不同基线HBsAg水平患者HBsAg清除率比较

Table 1. Comparison of HBsAg clearance rate in patients with different baseline HBsAg levels

组别	24周清除率(%)	48周清除率(%)	96周清除率(%)
基线HBsAg＜500 IU/mL组	31.1(23/74)	46.7(21/45)	82.1(23/28)
基线HBsAg 500~1 500 IU/mL组	3.5(2/57)¹⁾	9.4(3/32)¹⁾	14.8(4/27)¹⁾
基线HBsAg 1 501~5 000 IU/mL组	0.8(1/132)¹⁾	2.0(1/50)¹⁾	17.6(3/17)¹⁾
χ²值	52.265	32.764	30.918
P值	＜0.010	＜0.010	＜0.010
注：与基线HBsAg＜500 IU/mL组比较，P＜0.001。

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表 2 不同既往治疗情况及治疗方案患者HBsAg清除率比较

Table 2. Comparison of HBsAg clearance rate in patients with different previous treatment conditions and treatment regimens

组别	年龄(岁)	男/女(例)	基线HBeAg水平(PEI U/mL)	24周清除率(%)	48周清除率(%)	96周清除率(%)
治疗情况
初治组	33.8±9.3	43/30	3.0±0.9	4.0(1/25)	12.5(1/8)	20.0(1/5)
经治组	35.7±8.7	244/94	2.8±1.0	10.5(25/238)	20.2(24/119)	43.3(29/67)
统计值	t=1.671	χ²=5.029	t=1.576	χ²=1.074	χ²=0.279	χ²=1.038
P值	0.101	0.025	0.115	0.300	0.597	0.308
治疗方案
IFN单用组	34.8±10.5	70/36	2.6±1.2	11.9(7/59)	28.1(9/32)	52.6(10/19)
IFN联用组	36.5±8.3	217/88	2.8±0.9	9.3(19/204)	16.8(16/95)	37.7(20/53)
统计值	t=1.691	χ²=0.975	t=1.799	χ²=0.334	χ²=1.927	χ²=1.277
P值	0.092	0.323	0.073	0.563	0.165	0.258
注：基线抗原水平取lg值后统计。

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