基于Meta分析的兩種方案抗乙肝肝纖維化臨床療效的研究
發(fā)布時(shí)間：2018-09-06 11:53
【摘要】：目的:慢性乙型病毒性肝炎常規(guī)的抗病毒方案包括核苷/核苷酸類似物及干擾素α,在抗病毒過程中,是否會(huì)對纖維化有影響,不同的文獻(xiàn)報(bào)道不一。因此,我們用Meta分析的方法探討兩種方案(干擾素α方案以及扶正化瘀膠囊聯(lián)合核苷酸類藥物方案)抗乙肝肝纖維化的臨床療效。方法:用計(jì)算機(jī)檢索相關(guān)期刊論文(CNKI)、中國生物醫(yī)學(xué)數(shù)據(jù)庫(CBM)、萬方學(xué)術(shù)期刊全文數(shù)據(jù)庫(Wan Fang)、重慶維普(CQVIP)、PubMed、Embase等數(shù)據(jù)庫以及手工檢索的方法,取得干擾素α治療慢性乙型病毒性肝炎、乙型肝炎肝纖維化、乙型肝炎肝硬化的臨床隨機(jī)對照試驗(yàn)文獻(xiàn)、半隨機(jī)對照試驗(yàn)文獻(xiàn)以及扶正化瘀膠囊聯(lián)合核苷酸類治療慢性乙型病毒性肝炎、乙型肝炎肝纖維化、乙型肝炎肝硬化的臨床隨機(jī)對照試驗(yàn)文獻(xiàn),所有檢索時(shí)間均為自建庫-2016年11月30日。采用Jadad評分法進(jìn)行文獻(xiàn)質(zhì)量評價(jià),提取、篩選并最終納入文獻(xiàn)后,運(yùn)用RevMan5.0軟件進(jìn)行Meta分析。計(jì)數(shù)資料用比值比(OR),計(jì)量資料用均數(shù)差(MD)或標(biāo)準(zhǔn)均數(shù)差(SMD),計(jì)算95%可信區(qū)間(CI)。納入文獻(xiàn)異質(zhì)性檢驗(yàn)結(jié)果P0.05,I250%采用固定效應(yīng)模型作Meta分析;異質(zhì)性檢驗(yàn)結(jié)果P≤0.05,I2≥50%,則采用隨機(jī)效應(yīng)模型。采用漏斗圖評價(jià)納入研究是否存在發(fā)表偏倚。結(jié)果:(1)共納入干擾素α治療慢性乙型肝炎、慢性乙型肝炎后肝纖維化、慢性乙型肝炎后肝硬化臨床隨機(jī)對照試驗(yàn)812例,其中試驗(yàn)組425例,對照組387例,Meta分析結(jié)果顯示,在改善透明質(zhì)酸(HA)、層黏連蛋白(LN)、Ⅲ型前膠原(PC-Ⅲ)、IV型膠原(IV-C)方面干擾素α治療組優(yōu)于無干擾素α治療的對照組[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,干擾素α治療組與無干擾素α治療的對照組無明顯差異[Z=1.59,P=0.10,MD=-5.59,95%CI(-12.32,1.15)];HBeAg陰轉(zhuǎn)率方面,干擾素α治療組優(yōu)于無干擾素α治療的對照組[Z=7.54,P0.00001,OR=6.76,95%CI(4.12,11.12)];HBV-DNA陰轉(zhuǎn)率方面,干擾素α治療組優(yōu)于無干擾素α治療的對照組[Z=6.43,P0.00001,OR=8.64,95%CI(4.48,16.68)]。(2)納入扶正化瘀膠囊聯(lián)合核苷酸類治療慢性乙型病毒性肝炎、乙型肝炎肝纖維化、乙型肝炎肝硬化臨床隨機(jī)對照試驗(yàn)10項(xiàng),共896名患者,其中扶正化瘀膠囊聯(lián)合核苷酸類試驗(yàn)組472例,對照組424例。Meta分析結(jié)果顯示:在改善透明質(zhì)酸(HA)水平方面扶正化瘀膠囊聯(lián)合核苷酸類治療組優(yōu)于單用核苷酸對照組[Z=5.24,P0.00001,SMD=-0.78,95%CI(-1.07,-0.49)];改善層黏連蛋白(LN)方面扶正化瘀膠囊聯(lián)合核苷酸類治療組優(yōu)于單用核苷酸對照組[Z=4.09,P0.0001,SMD=-0.76,95%CI(-1.12,-0.39)];Ⅲ型前膠原(PC-Ⅲ)改善方面扶正化瘀膠囊聯(lián)合核苷酸類治療組優(yōu)于單用核苷酸對照組[Z=8.46,P0.00001,SMD=-0.65,95%CI(-0.80,-0.50)];IV型膠原(IV-C)改善方面扶正化瘀膠囊聯(lián)合核苷酸類治療組優(yōu)于單用核苷酸對照組[Z=10.83,P0.00001,SMD=-0.84,95%CI(-1.00,-0.69)];門靜脈內(nèi)徑改善方面扶正化瘀膠囊聯(lián)合核苷酸類治療組優(yōu)于單用核苷酸對照組[Z=2.66,P=0.008,SMD=-1.56,95%CI(-0.97,-0.15)];脾臟厚度改善方面扶正化瘀膠囊聯(lián)合核苷酸類治療組優(yōu)于單用核苷酸對照組[Z=3.93,P0.0001,SMD=-1.08,95%CI(-1.62,-0.54)];Fibroscan測得肝臟硬度值的改善方面扶正化瘀膠囊聯(lián)合核苷酸類治療組與單用核苷酸對照組比較無統(tǒng)計(jì)學(xué)意義[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膠囊聯(lián)合核苷酸類治療組優(yōu)于單用核苷酸對照組[Z=2.36,P=0.02,SMD=-6.98,95%CI(-12.78,-1.19)];HBeAg陰轉(zhuǎn)率方面扶正化瘀膠囊聯(lián)合核苷酸類治療組與單用核苷酸對照組比較無明顯差異[Z=1.91,P=0.06,OR=1.58,95%CI(0.99,2.53)];HBV-DNA陰轉(zhuǎn)率方面扶正化瘀膠囊聯(lián)合核苷酸類治療組優(yōu)于單用核苷酸對照組[Z=2.51,P=0.01,OR=1.63,95%CI(1.11,2.39)]。結(jié)論:Meta分析結(jié)果表明,干擾素α具有抗乙肝肝纖維化的臨床療效;扶正化瘀膠囊聯(lián)合核苷酸類在治療乙型肝炎肝纖維化的療效優(yōu)于單純使用核苷酸類,均值得進(jìn)一步推廣。由于受文獻(xiàn)質(zhì)量和數(shù)量的影響,目前相關(guān)臨床隨機(jī)對照試驗(yàn)相對較少,還需組織多中心、大樣本、高質(zhì)量和以肝組織穿刺活檢作為最終療效判定標(biāo)準(zhǔn)的臨床隨機(jī)對照試驗(yàn)進(jìn)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.
【學(xué)位授予單位】：廣西中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R512.62;R575.2
[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.
【學(xué)位授予單位】：廣西中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R512.62;R575.2
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