慢性乙型肝炎患者联合应用核苷(酸)类似物与干扰素治疗对肝脏组织学改善的Meta分析

肝脏 ›› 2025, Vol. 30 ›› Issue (5): 638-644.

慢性乙型肝炎患者联合应用核苷(酸)类似物与干扰素治疗对肝脏组织学改善的Meta分析

史立臣, 李舜, 孟彤彤, 黄澄, 王皓, 徐小倩, 贾继东, 孔媛媛

100050 首都医科大学附属北京友谊医院/北京市临床医学研究所临床流行病学与循证医学研究室(史立臣,李舜,黄澄,王皓,徐小倩,孔媛媛);首都医科大学附属北京友谊医院肝病中心(孟彤彤,贾继东);首都医科大学临床流行病学与临床试验学系(史立臣,黄澄,贾继东,孔媛媛)

收稿日期:2025-02-10 出版日期:2025-05-31 发布日期:2025-07-04
通讯作者: 孔媛媛,Email: kongyy@ccmu.edu.cn;贾继东,Email: Jia_jd@ccmu.edu.cn
作者简介:共同第一作者:李舜
基金资助:
国家重点研发计划(2023YFC2306902,2023YFC2306900);北京市卫生健康委高层次公共卫生技术人才建设项目(学科骨干-010-018);首都医科大学附属北京友谊医院“友谊种子计划”(YYZZ202254)

Histological improvement in chronic hepatitis B patients treated with nucleos(t)ide analogues combined with (pegylated-) interferon: a systematic review and Meta-analysis

SHI Li-chen^1,3, LI Shun¹, MENG Tong-tong², HUANG Cheng^1,3, WANG Hao¹, XU Xiao-qian¹, JIA Ji-dong^2,3, KONG Yuan-yuan^1,3

1. Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Research Institute, Beijing 100050, China;
2. Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing 100050, China;
3. Department of Clinical Epidemiology and Clinical Trial, Capital Medical University, Beijing 100050, China

Received:2025-02-10 Online:2025-05-31 Published:2025-07-04
Contact: KONG Yuan-yuan, Email: kongyy@ccmu.edu.cn; JIA Ji-dong, Email: Jia_jd@ccmu.edu.cn

摘要/Abstract

摘要： 目的评价核苷(酸)类似物(NAs)与干扰素(IFN)联合治疗慢性乙型肝炎(CHB)患者的肝脏组织学改善效果。方法检索PubMed、Embase和Cochrane数据库,收集NAs和IFN联合与单药治疗CHB患者的随机对照试验和非随机干预性研究(检索截至2024年5月31日)。结果共纳入14项研究(13项随机对照试验和1项非随机干预性研究),包括1411例患者。联合治疗与NAs单药治疗相比,肝组织炎症坏死改善率(RR=1.07, 95%CI 0.82～1.40)和肝纤维化改善率(RR=1.00, 95%CI 0.71～1.40)差异均无统计学意义。与IFN单药治疗相比,肝组织炎症坏死改善率(RR=1.88, 95%CI 0.91～3.90)差异无统计学意义。在第75百分位年龄≥45岁的研究中,相比IFN单药治疗,联合治疗显著提高了肝组织炎症坏死改善率(RR=3.02, 95%CI 1.49～6.16)。在基线HBV DNA平均水平≥7 log₁₀ U/mL的研究中,相比NAs单药治疗,联合治疗显著提高了肝组织炎症坏死改善率(RR=1.41, 95%CI 1.07～1.87)和肝纤维化改善率(RR=1.55, 95%CI 1.08～2.22)。结论 NAs联合IFN治疗在肝组织炎症坏死和纤维化改善方面疗效与单药治疗相似,但在纳入年龄较高或基线HBV DNA水平较高的研究中,联合治疗较单药治疗的肝组织学改善更显著。

关键词: 慢性乙型肝炎, 核苷(酸)类似物, 干扰素, 肝组织炎症坏死, 肝纤维化, Meta分析

Abstract: Objective To evaluate the efficacy of nucleos(t)ide analogs (NAs) and (pegylated-) interferon (IFN) combination therapy in histological improvement in chronic hepatitis B (CHB) patients. Methods For comparing combination therapy with NAs and IFN versus either NAs or IFN monotherapy for CHB treatment, we searched randomized controlled trials (RCTs) and nonrandomized studies of interventions (NRSIs) in PubMed, Embase, and the Cochrane Library up to May 31, 2024. Results A total of 14 studies (13RCTs and 1 NRSI) involving 1411 patients were included. There were no statistically significant differences in the improvement of liver necroinflammation rate (RR=1.07, 95% CI: 0.82-1.40) or liver fibrosis rate (RR=1.00, 95% CI: 0.71-1.40) between NAs-IFN combination therapy and NAs monotherapy. Similarly, there were no statistically significant difference in the improvement of liver necroinflammation rate (RR=1.88, 95% CI: 0.91-3.90) between NAs-IFN combination therapy and IFN monotherapy. However, in studies recruiting patients with 75th percentile of age ≥45 years old, combination therapy significantly improved liver necroinflammation rate than IFN monotherapy (RR=3.02, 95% CI: 1.49-6.16). In studies with a baseline mean HBV DNA level of ≥7 log₁₀ IU/mL, combination therapy significantly improved the liver necroinflammation rate (RR=1.41, 95% CI: 1.07-1.87) and liver fibrosis rate (RR=1.55, 95% CI: 1.08-2.22) than NAs monotherapy. Conclusion The combination therapy of NAs and IFN shows similar efficacy to monotherapy in improving liver necroinflammation and fibrosis. However, in studies involving older patients or those with higher baseline HBV DNA levels, the combination therapy demonstrates a significant advantage in histological improvement compared to NAs monotherapy.

Key words: Chronic hepatitis B, Nucleostide analogs, Interferon, Liver necroinflammation, Liver fibrosis, Meta-analysis

史立臣, 李舜, 孟彤彤, 黄澄, 王皓, 徐小倩, 贾继东, 孔媛媛. 慢性乙型肝炎患者联合应用核苷(酸)类似物与干扰素治疗对肝脏组织学改善的Meta分析[J]. 肝脏, 2025, 30(5): 638-644.

SHI Li-chen, LI Shun, MENG Tong-tong, HUANG Cheng, WANG Hao, XU Xiao-qian, JIA Ji-dong, KONG Yuan-yuan. Histological improvement in chronic hepatitis B patients treated with nucleos(t)ide analogues combined with (pegylated-) interferon: a systematic review and Meta-analysis[J]. Chinese Hepatolgy, 2025, 30(5): 638-644.

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