Ali Syed H, Shah Muhammad H, Roy Sakshi, Bharadwaj Hareesha R, Tan Joecelyn K, Rao Medha S, Fuad Muhtasim, Ahluwalia Arjun, Gaur Aditya, Dalal Priyal, Dhali Arkadeep, Gopakumar Harishankar
Faculty of Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan.
School of Medicine, Queen's University Belfast, Belfast, United Kingdom.
J Clin Exp Hepatol. 2025 Jul-Aug;15(4):102541. doi: 10.1016/j.jceh.2025.102541. Epub 2025 Mar 19.
Chronic hepatitis B virus remains a significant cause of liver disease in the developing world, leading to sequelae such as hepatocellular carcinoma. While entecavir (ETV) serves as a first-line treatment, its growing resistance rates underscore the need to explore viable alternatives. Tenofovir disoproxil fumarate (TDF) monotherapy and entecavir plus tenofovir (TDF + ETV) combination therapy are both employed as treatments, but one's efficacy over another is in question. This meta-analysis aims to investigate any primacy of either treatment.
We conducted a comprehensive literature search across PubMed/Medline, Embase, Cochrane Central, Web of Science, and China National Knowledge Infrastructure from inception till 7th October 2024. Studies comparing the safety and efficacy of TDF monotherapy versus TDF + ETV combination therapy in patients resistant to entecavir were considered. Data about the virologic response (VR), virologic breakthrough, HbeAg seroconversion, HbeAg/HbsAg seroclearance, and alanine aminotransferase normalization were extracted. Relative risks (RRs) and their corresponding 95% confidence intervals (CIs) were calculated, pooled, and analyzed in a random-effects model. -value <0.05 was regarded as significant for all analyses.
Nine studies, comprising 335 patients undergoing monotherapy and 352 patients undergoing combination therapy, satisfied the criteria. TDF + ETV combination therapy was found slightly advantageous to TDF monotherapy, stimulating a VR at 48 weeks (RR 1.081 95% CI: [1.001-1.167] = 0.046, I2 = 0%), along with the HbeAg seroconversion rate (RR 1.711 95% CI: [1.005-2.913] = 0.048, I2 = 0%). There were no significant adverse events in individual studies to warrant a meta-analysis.
TDF + ETV shows slightly better efficacy to TDF monotherapy over a 48-week treatment regimen, with minimal safety concerns. However, further high-quality studies like randomized controlled trials are needed to further solidify conclusions, with this meta-analysis only achieving borderline significances.
This review is registered on the PROSPERO database (ID: CRD42024581443).
慢性乙型肝炎病毒仍是发展中世界肝脏疾病的一个重要病因，可导致肝细胞癌等后遗症。虽然恩替卡韦（ETV）是一线治疗药物，但其耐药率不断上升凸显了探索可行替代方案的必要性。替诺福韦酯（TDF）单药治疗和恩替卡韦联合替诺福韦（TDF + ETV）联合治疗均被用作治疗方法，但哪种疗法的疗效更佳尚存在疑问。本荟萃分析旨在研究两种治疗方法中是否存在任何一种具有优势。
我们对PubMed/Medline、Embase、Cochrane Central、Web of Science和中国知网进行了全面的文献检索，检索时间跨度从数据库建立至2024年10月7日。纳入比较TDF单药治疗与TDF + ETV联合治疗对恩替卡韦耐药患者安全性和疗效的研究。提取有关病毒学应答（VR）、病毒学突破、HbeAg血清学转换、HbeAg/HbsAg血清清除以及丙氨酸氨基转移酶恢复正常的数据。计算相对风险（RRs）及其相应的95%置信区间（CIs），并在随机效应模型中进行合并和分析。所有分析中，P值<0.05被视为具有统计学意义。
9项研究符合标准，其中335例患者接受单药治疗，352例患者接受联合治疗。结果发现，TDF + ETV联合治疗比TDF单药治疗略具优势，在48周时能促进病毒学应答（RR 1.081，95% CI：[1.001 - 1.167]，P = 0.046，I2 = 0%），同时HbeAg血清学转换率也更高（RR 1.711，95% CI：[1.005 - 2.913]，P = 0.048，I2 = 0%）。各研究中均未出现需要进行荟萃分析的显著不良事件。
在48周的治疗方案中，TDF + ETV的疗效略优于TDF单药治疗，且安全性问题极小。然而，由于本荟萃分析仅达到临界显著性，因此需要进一步开展高质量研究，如随机对照试验，以进一步巩固结论。
本综述已在PROSPERO数据库注册（ID：CRD42024581443）。
