六味五灵片联合核苷(酸)类药物治疗慢性乙型肝炎肝纤维化的系统评价

Systematic evaluation of Liuweiwuling Tablets for treatment of liver fibrosis resulting from chronic hepatitis B

系统评价六味五灵片联合核苷(酸)类药物治疗慢性乙型肝炎肝纤维化有效性及安全性。计算机检索Pubmed、Embase、Cochrane Library(2015年第9期)、中国生物医学数据库(CBM)、中国期刊全文数据库(CNKI)、中文科技期刊全文数据库(VIP)、万方数据在线知识服务平台,全面收集有关六味五灵片联合核苷(酸)类药物治疗慢性乙型肝炎肝纤维化的随机对照试验(RCT),检索时限均从建库至2015年10月29日。由2位评价员按照纳入与排除标准独立筛选文献、提取资料和评价纳入研究的方法学质量后,采用Rev Man5.3软件进行Meta分析。最终纳入7个RCTs,共1 021例慢性乙型肝炎肝纤维化患者,其中治疗组529例,对照组492例。分析结果显示:与单用核苷(酸)类药物相比,六味五灵片联合核苷(酸)类药物不仅可降低慢性乙型肝炎肝纤维化患者血清肝纤维化指标:HA[SMD=-1.26,95%CI(-1.92,-0.59),P=0.000 2]、LN[SMD=-1.55,95%CI(-2.27,-0.83),P<0.000 1]、PC-III[SMD=-1.39,95%CI(-2.21,-0.58),P=0.000 8]、IV-C[SMD=-1.49,95%CI(-2.25,-0.72),P=0.000 1];还可以改善肝功能生化指标:ALT[SMD=-1.17,95%CI(-1.41,-0.94),P<0.000 01]、AST[SMD=-1.25,95%CI(-1.54,-0.96),P<0.000 01]、TBIL[SMD=-0.87,95%CI(-1.21,-0.53),P<0.000 01];提高临床总有效率[OR=4.59,95%CI(2.05,10.25),P=0.000 2];但并不能提高HBV DNA转阴率[OR=1.51,95%CI(0.96,2.39),P=0.08];且无明显不良反应报道。六味五灵片联合核苷(酸)类药物可明显改善患者肝功能,抑制肝纤维化,提高临床总有效率,且不良反应少、耐受性较好;虽然近年来RCTs研究的数量和质量有逐年上升的趋势,但仍需从临床设计的科学性、报告的规范性等诸多环节来提高研究水平。

Objective To systematicly evaluate the efficacy and safety of Liuweiwuling Tablets combined with nucleotide drugs for the treatment of liver fibrosis resulting from chronic hepatitis B. Methods Major databases（such as Pubmed, Embase, Cochrane Library（Issue 9, 2015）, Chinese Biomedical Database（CBM）, China National Knowledge Infrastructure（CNKI）, VIP, and Wan Fang Data were searched from their inception to September 9, 2015 to collect comprehensively randomized controlled trials（RCT） of Liuweiwuling Tablets combined with nucleotide drugs on the treatment of liver fibrosis resulting from chronic hepatitis B. After two reviewers separately screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of the included studies, data were analyzed with Rev Man 5.3 software. Results The total seven RCTs were included. Among all 1 021 patients involved, 529 cases were in the treatment group, while the other 492 cases were in the control group. The findings showed that compared with using nucleotide drugs alone for antiviral treatment, Liuweiwuling Tablets combined with nucleotide drugs were more efficiently in downregulating serum liver fibrosis index HA [SMD =-1.26, 95% CI（-1.92,-0.59）, P = 0.000 2], LN [SMD =-1.55, 95% CI（-2.27,-0.83）, P 〈 0.000 1], PC-III [SMD =-1.39, 95% CI（-2.21,-0.58）, P = 0.000 8], IV-C [SMD =-1.49, 95% CI（-2.25,-0.72）, P = 0.0001]; improved the liver function ALT [SMD =-1.17, 95% CI（-1.41,-0.94）, P 〈 0.000 01], AST [SMD =-1.25, 95% CI（-1.54,-0.96）, P 〈 0.000 01], TBIL [SMD =-0.87, 95% CI（-1.21,-0.53）, P 〈 0.000 01]; increased total clinical effective rate [OR = 4.59, 95% CI（2.05, 10.25）, P = 0.000 2]. While no advantage was found in reducing the incidences of HBV DNA overcast [OR = 1.51, 95% CI（0.96, 2.39）, P = 0.08]; No significant adverse reactions were reported. Conclusion Liuweiwuling Tablets combined with nucleotide drugs could be effective in improving liver function, controlling liver fibrosis, and increasing total clinical effective rate while its antiviral efficacy approximate with using the nucleotide drugs alone, less adverse reaction, and better tolerability; Although in recent years, the quantity and quality of RCTs research have a rising trend year by year, but still need to be from the clinical design of scientific, the standardization of the report, and many other links to improve research level.