Department of Gastroenterology, Sunshine Union Hospital, Weifang, China.
Medicine (Baltimore). 2022 Aug 12;101(32):e30020. doi: 10.1097/MD.0000000000030020.
The compound Biejia-Ruangan tablet (CBRT), as an adjunctive therapy to entecavir, is a potential treatment for hepatic fibrosis (HF) in patients with chronic hepatitis B (HBV). However, the present study yielded inconsistent results. In this systematic review and meta-analysis, we comprehensively investigated the efficacy and safety of CBRT as an adjunctive modality to entecavir for the treatment of HBV infection complicated with HF.
We searched the Cochrane Library, PubMed, Embase, CNKI, VIP, CBM, and Wangfang databases through April 1, 2022, for randomized controlled trials (RCTs) assessing the effect and safety of CBRT as an adjunctive modality to entecavir for HBV complicated with HF. The primary outcomes were biochemical parameters of serum hyaluronic acid, laminin (LN), pretype-III collagen (PC-III), and type IV collagen (IV-C). The secondary outcomes were liver function indices of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBiL) levels, total effect rate, and occurrence rate of adverse events. Two researchers independently conducted study selection, data extraction, and quality assessment. Statistical analysis was performed using the RevMan 5.3 software.
Eight RCTs involving 747 patients were included. Compared with entecavir monotherapy, CBRT as an adjunctive therapy to entecavir exerted more encouraging effect in serum levels of hyaluronic acid (mean difference [MD] = -28.15; 95% confidence interval [CI]: -43.82 to -12.47; P < .001), LN (MD = -29.46; 95% CI: -50.69 to -8.23; P < .001), PC-III (MD = -11.83; 95% CI: -19.43 to -4.23; P < .001), and IV-C (MD = -19.62; 95% CI: -29.76 to -9.49; P < .001); levels of serum ALT (MD = -16.83; 95% CI: -26.30 to -7.36; P < .001), AST (MD = -20.52; 95% CI: -33.11 to -7.93; P < .001), and TBiL (MD = -7.54; 95% CI: -11.58 to -3.49; P < .001); and total effect rate (odds ratio = 3.53; 95% CI: 1.71-7.29; P < .001). Meta-analysis results also showed that CBRT as an adjunctive therapy to entecavir had a lower occurrence rate of adverse events (odds ratio = 0.54; 95% CI: 0.22-1.34; P < .001) than entecavir alone.
The results of this study showed that CBRT as an adjunctive modality to entecavir may benefit HBV patients complicated with HF. High-quality RCTs are needed to confirm the current findings in the future.
复方鳖甲软肝片（CBRT）作为恩替卡韦的辅助治疗药物，可能是治疗慢性乙型肝炎（HBV）患者肝纤维化（HF）的一种潜在方法。然而，目前的研究结果并不一致。在这项系统评价和荟萃分析中，我们全面研究了 CBRT 作为恩替卡韦辅助治疗药物治疗 HBV 合并 HF 的疗效和安全性。
我们检索了 Cochrane 图书馆、PubMed、Embase、CNKI、VIP、CBM 和万方数据库，截至 2022 年 4 月 1 日，以评估 CBRT 作为恩替卡韦辅助治疗药物治疗 HBV 合并 HF 的效果和安全性的随机对照试验（RCT）。主要结局指标为血清透明质酸、层粘连蛋白（LN）、前 III 型胶原（PC-III）和 IV 型胶原（IV-C）的生化参数。次要结局指标为血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和总胆红素（TBiL）水平的肝功能指标、总有效率和不良事件发生率。两名研究人员独立进行了研究选择、数据提取和质量评估。使用 RevMan 5.3 软件进行统计分析。
共纳入 8 项 RCT，涉及 747 名患者。与恩替卡韦单药治疗相比，CBRT 作为恩替卡韦的辅助治疗在血清透明质酸水平（MD=-28.15；95%CI：-43.82 至-12.47；P<.001）、LN（MD=-29.46；95%CI：-50.69 至-8.23；P<.001）、PC-III（MD=-11.83；95%CI：-19.43 至-4.23；P<.001）和 IV-C（MD=-19.62；95%CI：-29.76 至-9.49；P<.001）方面的疗效更为显著；血清 ALT（MD=-16.83；95%CI：-26.30 至-7.36；P<.001）、AST（MD=-20.52；95%CI：-33.11 至-7.93；P<.001）和 TBiL（MD=-7.54；95%CI：-11.58 至-3.49；P<.001）水平也有所降低；总有效率（OR=3.53；95%CI：1.71-7.29；P<.001）也更高。荟萃分析结果还表明，CBRT 作为恩替卡韦的辅助治疗药物，不良事件的发生率（OR=0.54；95%CI：0.22-1.34；P<.001）低于恩替卡韦单药治疗。
本研究结果表明，CBRT 作为恩替卡韦的辅助治疗方法可能有益于 HBV 合并 HF 的患者。未来需要高质量的 RCT 来证实目前的研究结果。
