基于Meta分析的两种方案抗乙肝肝纤维化临床疗效的研究

发布时间：2018-09-06 11:53

【摘要】：目的:慢性乙型病毒性肝炎常规的抗病毒方案包括核苷/核苷酸类似物及干扰素α,在抗病毒过程中,是否会对纤维化有影响,不同的文献报道不一。因此,我们用Meta分析的方法探讨两种方案(干扰素α方案以及扶正化瘀胶囊联合核苷酸类药物方案)抗乙肝肝纤维化的临床疗效。方法:用计算机检索相关期刊论文(CNKI)、中国生物医学数据库(CBM)、万方学术期刊全文数据库(Wan Fang)、重庆维普(CQVIP)、PubMed、Embase等数据库以及手工检索的方法,取得干扰素α治疗慢性乙型病毒性肝炎、乙型肝炎肝纤维化、乙型肝炎肝硬化的临床随机对照试验文献、半随机对照试验文献以及扶正化瘀胶囊联合核苷酸类治疗慢性乙型病毒性肝炎、乙型肝炎肝纤维化、乙型肝炎肝硬化的临床随机对照试验文献,所有检索时间均为自建库-2016年11月30日。采用Jadad评分法进行文献质量评价,提取、筛选并最终纳入文献后,运用RevMan5.0软件进行Meta分析。计数资料用比值比(OR),计量资料用均数差(MD)或标准均数差(SMD),计算95%可信区间(CI)。纳入文献异质性检验结果P0.05,I250%采用固定效应模型作Meta分析;异质性检验结果P≤0.05,I2≥50%,则采用随机效应模型。采用漏斗图评价纳入研究是否存在发表偏倚。结果:(1)共纳入干扰素α治疗慢性乙型肝炎、慢性乙型肝炎后肝纤维化、慢性乙型肝炎后肝硬化临床随机对照试验812例,其中试验组425例,对照组387例,Meta分析结果显示,在改善透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前胶原(PC-Ⅲ)、IV型胶原(IV-C)方面干扰素α治疗组优于无干扰素α治疗的对照组[Z=7.39,P0.00001,SMD=-1.61,95%CI(-2.03,-1.18)]、[Z=6.59,P0.00001,SMD=-0.88,95%CI(-1.15,-0.62)]、[Z=4.54,P0.00001,SMD=-1.09,95%CI(-1.56,-0.62)]、[Z=5.67,P0.00001,SMD=-1.08,95%CI(-1.45,-0.70)];ALT水平改善方面,干扰素α治疗组与无干扰素α治疗的对照组无明显差异[Z=1.59,P=0.10,MD=-5.59,95%CI(-12.32,1.15)];HBeAg阴转率方面,干扰素α治疗组优于无干扰素α治疗的对照组[Z=7.54,P0.00001,OR=6.76,95%CI(4.12,11.12)];HBV-DNA阴转率方面,干扰素α治疗组优于无干扰素α治疗的对照组[Z=6.43,P0.00001,OR=8.64,95%CI(4.48,16.68)]。(2)纳入扶正化瘀胶囊联合核苷酸类治疗慢性乙型病毒性肝炎、乙型肝炎肝纤维化、乙型肝炎肝硬化临床随机对照试验10项,共896名患者,其中扶正化瘀胶囊联合核苷酸类试验组472例,对照组424例。Meta分析结果显示:在改善透明质酸(HA)水平方面扶正化瘀胶囊联合核苷酸类治疗组优于单用核苷酸对照组[Z=5.24,P0.00001,SMD=-0.78,95%CI(-1.07,-0.49)];改善层黏连蛋白(LN)方面扶正化瘀胶囊联合核苷酸类治疗组优于单用核苷酸对照组[Z=4.09,P0.0001,SMD=-0.76,95%CI(-1.12,-0.39)];Ⅲ型前胶原(PC-Ⅲ)改善方面扶正化瘀胶囊联合核苷酸类治疗组优于单用核苷酸对照组[Z=8.46,P0.00001,SMD=-0.65,95%CI(-0.80,-0.50)];IV型胶原(IV-C)改善方面扶正化瘀胶囊联合核苷酸类治疗组优于单用核苷酸对照组[Z=10.83,P0.00001,SMD=-0.84,95%CI(-1.00,-0.69)];门静脉内径改善方面扶正化瘀胶囊联合核苷酸类治疗组优于单用核苷酸对照组[Z=2.66,P=0.008,SMD=-1.56,95%CI(-0.97,-0.15)];脾脏厚度改善方面扶正化瘀胶囊联合核苷酸类治疗组优于单用核苷酸对照组[Z=3.93,P0.0001,SMD=-1.08,95%CI(-1.62,-0.54)];Fibroscan测得肝脏硬度值的改善方面扶正化瘀胶囊联合核苷酸类治疗组与单用核苷酸对照组比较无统计学意义[Z=1.15,P=0.25,MD=-6.51,95%CI(-17.59,4.58)];ALT水平改善方面扶正化瘀胶囊联合核苷酸类治疗组优于单用核苷酸对照组[Z=2.36,P=0.02,SMD=-6.98,95%CI(-12.78,-1.19)];HBeAg阴转率方面扶正化瘀胶囊联合核苷酸类治疗组与单用核苷酸对照组比较无明显差异[Z=1.91,P=0.06,OR=1.58,95%CI(0.99,2.53)];HBV-DNA阴转率方面扶正化瘀胶囊联合核苷酸类治疗组优于单用核苷酸对照组[Z=2.51,P=0.01,OR=1.63,95%CI(1.11,2.39)]。结论:Meta分析结果表明,干扰素α具有抗乙肝肝纤维化的临床疗效;扶正化瘀胶囊联合核苷酸类在治疗乙型肝炎肝纤维化的疗效优于单纯使用核苷酸类,均值得进一步推广。由于受文献质量和数量的影响,目前相关临床随机对照试验相对较少,还需组织多中心、大样本、高质量和以肝组织穿刺活检作为最终疗效判定标准的临床随机对照试验进一步研究。
[Abstract]:Objective: Conventional antiviral regimens for chronic viral hepatitis B include nucleoside/nucleotide analogues and interferon alpha. There are different reports on the effect of IFN alpha on fibrosis in the course of antiviral therapy. Therefore, two regimens (IFN alpha regimen and Fuzheng Huayu capsule combined with nucleotides) were studied by meta analysis. METHODS: CNKI, CBM, Wan Fang, CQVIP, PubMed, Embase and other databases were searched by computer to obtain interferon alpha in the treatment of chronic hepatitis B. Literatures on clinical randomized controlled trials of toxic hepatitis, hepatitis B liver fibrosis, hepatitis B cirrhosis, semi-randomized controlled trials, and clinical randomized controlled trials of Fuzheng Huayu capsule combined with nucleotides in the treatment of chronic hepatitis B, hepatitis B liver fibrosis and hepatitis B cirrhosis were retrieved at all times. In order to build the database-November 30, 2016, the Jadad scoring method was used to evaluate the quality of literature, extract, screen and finally incorporate into the literature. The software RevMan 5.0 was used for meta-analysis. Fixed-effect model was used for meta-analysis in 250% of the patients; heterogeneity test results P < 0.05 and I2 < 50% were used for random-effect model. Funnel plot was used to assess whether there was publication bias in the included study. Results: (1) Interferon-alpha was included in the treatment of chronic hepatitis B, hepatic fibrosis after chronic hepatitis B, and cirrhosis after chronic hepatitis B. The results of Meta-analysis showed that IFN-alpha treatment group was superior to the control group in improving hyaluronic acid (HA), laminin (LN), type III procollagen (PC-III), type IV collagen (IV-C) [Z = 7.39, P 0.00001, SMD =-1.61, 95% CI (-2.03, -1.18)], [Z = 6.59, P 0.00001, SMD = SMD = 1.18]. -0.88,95% CI (-1.88,95% CI (-1.88,95% CI (-1.15, -0.62)], [Z = 4.54, P 0.00001, SMD =-1.54, P 0.00001, SMD =-1.06, 95% CI (-1.56, -0.62)], [Z = 5.67, P 0.00001, P 0.00001, SMD =-1.08, 95% CI (-1.45, -0.70)], [Z = 5.67, P =0.10, MD =-5.56, MD =-5.59, 95% CI (-5.59, 95% CI (-59, 95% CI (-5.59, 95% CI (-59 HBeAg negative conversion rate, interferon alpha treatment group Compared with the control group without interferon alpha treatment [Z = 7.54, P 0.00001, OR = 6.76, 95% CI (4.12, 11.12)]; HBV-DNA negative conversion rate, interferon alpha treatment group was better than the control group without interferon alpha treatment [Z = 6.43, P 0.00001, OR = 8.64, 95% CI (4.48, 16.68)]. (2) Fuzheng Huayu capsule combined with nucleotides in the treatment of chronic hepatitis B, hepatitis B A total of 896 patients were enrolled in 10 randomized controlled trials of hepatic fibrosis and hepatitis B cirrhosis, including 472 cases of Fuzheng Huayu capsule combined with nucleotides test group and 424 cases of control group. SMD = - 0.78,95% CI (- 1.07, - 0.49)]; Fuzheng Huayu capsule combined with nucleotides treatment group was superior to nucleotides control group in improving laminin (LN) [Z = 4.09, P 0.0001, SMD = - 0.76, 95% CI (- 1.12, - 0.39)]; Fuzheng Huayu capsule combined with nucleotides treatment group was superior to nucleotides control group in improving type III procollagen (PC - III). [Z = 8.46, P 0.00001, SMD = - 0.65, 95% CI (- 0.80, - 0.50)]; Fuzheng Huayu capsule combined with nucleotide treatment group was superior to nucleotide control group [Z = 10.83, P 0.00001, SMD = - 0.84, 95% CI (- 1.00, - 0.69)]; portal vein diameter improvement of Fuzheng Huayu capsule combined with nucleotide treatment group was superior to nucleotide control group. Group [Z = 2.66, P = 0.008, SMD = - 1.56, 95% CI (- 0.97, - 0.15)]; the improvement of spleen thickness in the Fuzheng Huayu capsule combined with nucleotides treatment group was superior to the nucleotides control group [Z = 3.93, P 0.0001, SMD = - 1.08, 95% CI (- 1.62, - 0.54)]; the improvement of liver stiffness measured by Fibroscan in the Fuzheng Huayu capsule combined with nucleotides treatment group and nucleotides treatment group alone [Z = 3.93, P 0.0001, SMD = - 1.08, 95% CI (- There was no significant difference between the acid control group [Z = 1.15, P = 0.25, MD = - 6.51, 95% CI (- 17.59, 4.58)]; the improvement of ALT level in the Fuzheng Huayu capsule combined with nucleotides treatment group was better than that in the nucleotide control group [Z = 2.36, P = 0.02, SMD = - 6.98, 95% CI (- 12.78, - 1.19)]; the negative conversion rate of HBeAg in the Fuzheng Huayu capsule combined with nucleotides treatment group was better than that in the nucleotide control group alone [Z = 2.36, P = 0.02, SMD = - 6 There was no significant difference between the nucleotide control group [Z = 1.91, P = 0.06, OR = 1.58, 95% CI (0.99, 2.53)]; the negative conversion rate of HBV-DNA in the Fuzheng Huayu capsule combined with nucleotide group was better than that in the nucleotide control group [Z = 2.51, P = 0.01, OR = 1.63, 95% CI (1.11, 2.39)]. Fuzheng Huayu Capsule combined with nucleotides is superior to nucleotides alone in the treatment of hepatitis B hepatic fibrosis, which is worthy of further promotion. Clinical randomized controlled trials of final curative effect criteria were further studied.
【学位授予单位】：广西中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R512.62;R575.2

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