肝动脉化疗栓塞术联合抗病毒治疗乙肝相关肝癌疗效的Meta分析
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摘要
目的从近期疗效和远期疗效以及对乙肝病毒、肝功能、甲胎蛋白的作用这几方面,系统评价以恩替卡韦抗病毒治疗联合肝动脉化疗栓塞术(TACE)对乙肝相关性肝癌的疗效。方法通过计算机于多个中外数据库检索恩替卡韦联合TACE治疗乙肝相关性肝癌的RCT(中文?)文献,截止日期为2018年7月1日,通过筛选最终纳入中文文献16篇,包括TACE联合恩替卡韦抗病毒(实验组)734例和单独TACE(对照组)696例,对其进行质量评价,并使用Stata 11进行Meta分析。结果 Meta分析显示实验组在ALT下降(P=0.011)、HBV DNA定量减少(P=0.000)、AFP变化(P=0.006)、1年生存率(P=0.001)及2年生存率(P=0.004)均优于对照组(P<0.05)。即联合恩替卡韦抗病毒治疗对TACE术后乙肝病毒有抑制作用,改善肝功能、抑制甲胎蛋白水平,并提高其近期疗效、远期生存情况。结论 HBV再激活是乙肝相关性肝癌治疗后复发的重要危险因素,多次TACE治疗能引起HBV再激活,故有必要联合抗病毒治疗以预防,降低HBV再激活发生率。联合恩替卡韦抗病毒治疗乙肝相关性肝癌可提高TACE的疗效,值得在临床中推广应用。
Objective To systematically evaluate the efficacy of antivirus therapy combined with hepatic arterialchemoembolization(TACE) in hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC) by META analysis, takingentecavir as an example,from the aspects of short-term and long-term efficacy as well as the effects on hepatitis B virus, liverfunction and alpha fetoprotein. Methods Randomized controlled clinical trials(RCTs) of entecavir combined with TACE intreatment of HBV-associated HCC were selected in Chinese and foreign databases. The deadline was July 1, 2018. SixteenChinese literatures,734 cases in the experimental group and 696 cases in the control group, were finally included throughscreening and quality evaluation, and meta analyzed by Stata 11. Results The results of META analysis showed that ALTchanges(P=0.011), HBV DNA changes(P=0.000), AFP changes(P=0.006), 1-year survival rate(P=0.001) and 2-yearsurvival rate(P=0.004) were better in the experimental group than in the control group, and P<0.05. That is, combined withentecavir could inhibit the HBV after TACE, improve the liver function, inhibit the level of AFP, and improve its short-termefficacy and long-term survival. Conclusion HBV reactivation is an important risk factor for HBV-associated liver cancerrecurrence after treatment. Multiple TACE treatments can cause HBV reactivation, so it is necessary to combine with antiviraltherapy to prevent and reduce the incidence of HBV reactivation.Combined with entecavir in the treatment of hepatocellularcarcinoma associated with hepatitis B can improve the efficacy of TACE and is worthy of clinical application.
Objective To systematically evaluate the efficacy of antivirus therapy combined with hepatic arterialchemoembolization(TACE) in hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC) by META analysis, takingentecavir as an example,from the aspects of short-term and long-term efficacy as well as the effects on hepatitis B virus, liverfunction and alpha fetoprotein. Methods Randomized controlled clinical trials(RCTs) of entecavir combined with TACE intreatment of HBV-associated HCC were selected in Chinese and foreign databases. The deadline was July 1, 2018. SixteenChinese literatures,734 cases in the experimental group and 696 cases in the control group, were finally included throughscreening and quality evaluation, and meta analyzed by Stata 11. Results The results of META analysis showed that ALTchanges(P=0.011), HBV DNA changes(P=0.000), AFP changes(P=0.006), 1-year survival rate(P=0.001) and 2-yearsurvival rate(P=0.004) were better in the experimental group than in the control group, and P<0.05. That is, combined withentecavir could inhibit the HBV after TACE, improve the liver function, inhibit the level of AFP, and improve its short-termefficacy and long-term survival. Conclusion HBV reactivation is an important risk factor for HBV-associated liver cancerrecurrence after treatment. Multiple TACE treatments can cause HBV reactivation, so it is necessary to combine with antiviraltherapy to prevent and reduce the incidence of HBV reactivation.Combined with entecavir in the treatment of hepatocellularcarcinoma associated with hepatitis B can improve the efficacy of TACE and is worthy of clinical application.
引文
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[3]CHEN C J,YANG H I,SU J,et al.Risk of hepatcellularcarcinoma across a biological gradient of serum hepatitis B virus DNA level[J].JAMA,2006,295(1):65-73.
[4]国家卫生和计划生育委员会办公厅.原发性肝癌诊疗规范(2017年版)[J].中国实用外科杂志,2017,37(07):705-720.
[5]肝细胞癌抗病毒治疗专家组.HBV/HCV相关性肝细胞癌抗病毒治疗专家共识[J].临床肿瘤学杂志,2014,19(5):452-459.
[6]European Association for the Study of the Liver.EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection[J].J Hepatol,2017.
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[8]ROBOTIN M C,KANSIL M Q,PORWAL M,et al.Communitybased prevention of hepatitis-B-related liver cancer:Australian insights[J].Bill World Health Organ,2014,92:374-379.
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[11]LI X,ZHONG X,CHEN Z H,et al.Effcacy of prophylactic entecavir for hepatitis b virusrelated hepatocellular carcinoma receiving transcatheter arterial chemoembolization[J].Asian Pacifc Journal of Cancer Prevention,2015,16(18):8665-8670.
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[13]张世同,金建军,白艳丽,等.TACE术后接受恩替卡韦治疗血清HBV DNA阴性的中晚期原发性肝癌患者生存率研究[J].实用肝脏病杂志,2018,21(1):100-103.
[14]丁杰雯,泽永革,段文鑫,等.恩替卡韦联合TACE术治疗乙肝相关性肝癌的疗效观察[J].西藏医药,2018,39(2):41-43.
[15]蒋世海,李万浪,吕永昌,等.恩替卡韦联合肝动脉化疗栓塞术对肝癌合并乙肝患者的疗效及乙肝病毒再激活的影响[J].肿瘤药学,2018,8(2):2015-2018.
[16]余景志,汪建成,张威,等.TACE联合恩替卡韦治疗乙型肝炎相关的原发性肝癌的疗效分析[J].实用癌症杂志,2017,32(8):1276-1282.
[17]林福煌,林碧泉,吴宁,等.抗乙肝病毒对肝癌TACE术后复发转移的治疗效果与免疫功能影响的研究[J].中华医院感染学杂志,2017,27(14):3196-3199.
[18]胡兴龙,王胜智,康志龙,等.乙型肝炎继发肝癌患者TACE术围术期使用恩替卡韦的临床观察[J].中国药房,2017,28(2):246-249.
[19]许红华.TACE联合抗病毒治疗乙肝相关性肝癌的效果分析[J].中国民康医学,2017,29(18):47-49.
[20]吴菊意.恩替卡韦联合介入治疗乙型肝炎相关原发性肝癌临床效果观察[J].中国实用医药,2016,11(16):173-174.
[21]王忠,刘启榆,杨伟,等.介入治疗联合抗病毒治疗乙肝相关肝癌的疗效分析[J].中华肿瘤防治杂志,2016,23(S1):158-159.
[22]杨阳,杨龙,魏燕,等.抗病毒联合TACE治疗乙肝病毒阴性肝癌的临床研究[J].中华肿瘤防治杂志,2016,23(1):25-29.
[23]谢湘平.抗病毒治疗乙型肝炎相关原发性肝癌患者临床疗效观察[J].海峡药学,2016,28(8):173-174.
[24]王丽君,卜文哲,陈华,等.TACE联合恩替卡韦治疗乙型肝炎相关原发性肝癌回顾性分析[J].中华肿瘤防治杂志,2014,10,21(20):1617-1622.
[25]郭锰.恩替卡韦联合介入治疗乙型肝炎相关原发性肝癌的临床研究[J].中国普通外科杂志,2014,23(7):898-903.
[26]王满,赵立群,徐峰,等.抗病毒治疗对经肝动脉化疗栓塞乙肝相关原发性肝癌的作用[J].实用医学杂志,2014,30(22):3620-3621.
[27]轩杰,马生录,唐江燕,等.恩替卡韦联合肝动脉化疗栓塞术治疗乙型肝炎相关中晚期肝癌患者的疗效观察[J].宁夏医学杂志,2013,35(10):947-948.
[28]秦菲,朱宏英,吴晓霞,等.恩替卡韦预防HBV相关性肝癌TACE术后肝损害的疗效分析[J].医学临床研究,2011,28(7):1249-1251.
[29]YEO W,CHAN PK,ZHONG S,et al.Frequency of hepatitis B virus reactivation in cancer patients undergoing cytotoxic chemotherapy:a prospective study of 626 patients with identification of risk factors[J].J Med Virol,2000,62(3):299-307.
[30]MA ZIMMERMAN,RM GHOBRIAL,MJ TONG,et al.Antiviral Prophylaxis and Recurrence of Hepatocellular Carcinoma Following Liver Transplantation in Patients With Hepatitis B[J].Transplantation Proceedings,2007,39:3276-3280.
[31]RAHBARI NN,MEHRABI A,MOLLBERG NM,et al.Hepatocellularcarcinoma:current management and perspectives for the future[J].Ann Surg,2011,253(3):453-469.
[32]SHI M,LU LG,FANG WQ,et al.Roles played by chemolipiodolization and embolization in chemoembolization for hepatocellular carcinoma:single-blind,randomized trial[J].J Natl Cancer Inst,2013,105(1):59-68.
[33]LI M,LU C,CHENG J,et al.Combination therapy with transarterial chemoembolization and interferon-alpha compared with transarterial chemoembolization alone for hepatitis B virus related unresectable hepatocellular carcinoma[J].J GastroenterolHepatol,2009,24(8):1437-1444.
[34]王骏成,劳向明.HBV相关肝癌TACE术后HBV DNA及肝功能变化的研究进展[J].新医学,2016,5(47):290-294.
[35]HUNG H H,SU C W,WU J C,et al.Reactivation of hepatitis B virus after transarterial chemo-embolization for hepatocellular carcinoma in one patient with negative hepatitis B surface antigen[J].JHepatol,2010,52(3):463-465.
[36]JANG J W,CHOI J Y,BAE S H,et al.Transarterial chemo-lipiodolization can reactivate hepatitis B virus replication in patients with hepatocellular carcinoma[J].J Hepatol,2004,41(3):427-435.
[37]倪全法,王晓光,俞鹏飞,等.原发性肝癌肝动脉化疗栓塞治疗后乙肝病毒再活化及其相关因素研究.肿瘤学杂志,2011,17(5):360-362.
[38]韩聚强,任永强,李国安,等.原发性肝癌微创介入治疗术后HBV再激活及相关影响因素研究.中国医学前沿杂志(电子版),2014,6(3):27-30.2018-09-26
[2]NATIONAL COMPREHENSUVE CANCER NETWORK.HepatobiliaryCancers(Version 1.2018)[OL].http://www.nccn.org,February 14,2018.
[3]CHEN C J,YANG H I,SU J,et al.Risk of hepatcellularcarcinoma across a biological gradient of serum hepatitis B virus DNA level[J].JAMA,2006,295(1):65-73.
[4]国家卫生和计划生育委员会办公厅.原发性肝癌诊疗规范(2017年版)[J].中国实用外科杂志,2017,37(07):705-720.
[5]肝细胞癌抗病毒治疗专家组.HBV/HCV相关性肝细胞癌抗病毒治疗专家共识[J].临床肿瘤学杂志,2014,19(5):452-459.
[6]European Association for the Study of the Liver.EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection[J].J Hepatol,2017.
[7]SARIN S K,KUMAR M,LAU G K,et al.Asian-Pacific clinical practice guidelines on the management of hepatitis B:a 2015 update[J].Hepatol Int,2016,10(1):1-98.
[8]ROBOTIN M C,KANSIL M Q,PORWAL M,et al.Communitybased prevention of hepatitis-B-related liver cancer:Australian insights[J].Bill World Health Organ,2014,92:374-379.
[9]QIU G P,LIU J.Micro RNA gene micro rna gene polymorphisms in evaluating therapeuticefficacy after transcatheter arterial chemoembolization for primary hepatocellular carcinoma[J].Genet Test Mol Biomarkers,2016,20(10):579-586.
[10]YUEN M F.Need to improve awareness and management of hepatitis B reactivation in patients receiving immunosuppressive therapy[J].HepatolInt,2016,10(1):102-105.
[11]LI X,ZHONG X,CHEN Z H,et al.Effcacy of prophylactic entecavir for hepatitis b virusrelated hepatocellular carcinoma receiving transcatheter arterial chemoembolization[J].Asian Pacifc Journal of Cancer Prevention,2015,16(18):8665-8670.
[12]MOHER D,PHAM B,JONES A,et al.Does quality of reportsofrandomizedtrials affect estimates of intervention efficacyreported in meta-analyses[J].Lancet,1998,3(52):609-613.
[13]张世同,金建军,白艳丽,等.TACE术后接受恩替卡韦治疗血清HBV DNA阴性的中晚期原发性肝癌患者生存率研究[J].实用肝脏病杂志,2018,21(1):100-103.
[14]丁杰雯,泽永革,段文鑫,等.恩替卡韦联合TACE术治疗乙肝相关性肝癌的疗效观察[J].西藏医药,2018,39(2):41-43.
[15]蒋世海,李万浪,吕永昌,等.恩替卡韦联合肝动脉化疗栓塞术对肝癌合并乙肝患者的疗效及乙肝病毒再激活的影响[J].肿瘤药学,2018,8(2):2015-2018.
[16]余景志,汪建成,张威,等.TACE联合恩替卡韦治疗乙型肝炎相关的原发性肝癌的疗效分析[J].实用癌症杂志,2017,32(8):1276-1282.
[17]林福煌,林碧泉,吴宁,等.抗乙肝病毒对肝癌TACE术后复发转移的治疗效果与免疫功能影响的研究[J].中华医院感染学杂志,2017,27(14):3196-3199.
[18]胡兴龙,王胜智,康志龙,等.乙型肝炎继发肝癌患者TACE术围术期使用恩替卡韦的临床观察[J].中国药房,2017,28(2):246-249.
[19]许红华.TACE联合抗病毒治疗乙肝相关性肝癌的效果分析[J].中国民康医学,2017,29(18):47-49.
[20]吴菊意.恩替卡韦联合介入治疗乙型肝炎相关原发性肝癌临床效果观察[J].中国实用医药,2016,11(16):173-174.
[21]王忠,刘启榆,杨伟,等.介入治疗联合抗病毒治疗乙肝相关肝癌的疗效分析[J].中华肿瘤防治杂志,2016,23(S1):158-159.
[22]杨阳,杨龙,魏燕,等.抗病毒联合TACE治疗乙肝病毒阴性肝癌的临床研究[J].中华肿瘤防治杂志,2016,23(1):25-29.
[23]谢湘平.抗病毒治疗乙型肝炎相关原发性肝癌患者临床疗效观察[J].海峡药学,2016,28(8):173-174.
[24]王丽君,卜文哲,陈华,等.TACE联合恩替卡韦治疗乙型肝炎相关原发性肝癌回顾性分析[J].中华肿瘤防治杂志,2014,10,21(20):1617-1622.
[25]郭锰.恩替卡韦联合介入治疗乙型肝炎相关原发性肝癌的临床研究[J].中国普通外科杂志,2014,23(7):898-903.
[26]王满,赵立群,徐峰,等.抗病毒治疗对经肝动脉化疗栓塞乙肝相关原发性肝癌的作用[J].实用医学杂志,2014,30(22):3620-3621.
[27]轩杰,马生录,唐江燕,等.恩替卡韦联合肝动脉化疗栓塞术治疗乙型肝炎相关中晚期肝癌患者的疗效观察[J].宁夏医学杂志,2013,35(10):947-948.
[28]秦菲,朱宏英,吴晓霞,等.恩替卡韦预防HBV相关性肝癌TACE术后肝损害的疗效分析[J].医学临床研究,2011,28(7):1249-1251.
[29]YEO W,CHAN PK,ZHONG S,et al.Frequency of hepatitis B virus reactivation in cancer patients undergoing cytotoxic chemotherapy:a prospective study of 626 patients with identification of risk factors[J].J Med Virol,2000,62(3):299-307.
[30]MA ZIMMERMAN,RM GHOBRIAL,MJ TONG,et al.Antiviral Prophylaxis and Recurrence of Hepatocellular Carcinoma Following Liver Transplantation in Patients With Hepatitis B[J].Transplantation Proceedings,2007,39:3276-3280.
[31]RAHBARI NN,MEHRABI A,MOLLBERG NM,et al.Hepatocellularcarcinoma:current management and perspectives for the future[J].Ann Surg,2011,253(3):453-469.
[32]SHI M,LU LG,FANG WQ,et al.Roles played by chemolipiodolization and embolization in chemoembolization for hepatocellular carcinoma:single-blind,randomized trial[J].J Natl Cancer Inst,2013,105(1):59-68.
[33]LI M,LU C,CHENG J,et al.Combination therapy with transarterial chemoembolization and interferon-alpha compared with transarterial chemoembolization alone for hepatitis B virus related unresectable hepatocellular carcinoma[J].J GastroenterolHepatol,2009,24(8):1437-1444.
[34]王骏成,劳向明.HBV相关肝癌TACE术后HBV DNA及肝功能变化的研究进展[J].新医学,2016,5(47):290-294.
[35]HUNG H H,SU C W,WU J C,et al.Reactivation of hepatitis B virus after transarterial chemo-embolization for hepatocellular carcinoma in one patient with negative hepatitis B surface antigen[J].JHepatol,2010,52(3):463-465.
[36]JANG J W,CHOI J Y,BAE S H,et al.Transarterial chemo-lipiodolization can reactivate hepatitis B virus replication in patients with hepatocellular carcinoma[J].J Hepatol,2004,41(3):427-435.
[37]倪全法,王晓光,俞鹏飞,等.原发性肝癌肝动脉化疗栓塞治疗后乙肝病毒再活化及其相关因素研究.肿瘤学杂志,2011,17(5):360-362.
[38]韩聚强,任永强,李国安,等.原发性肝癌微创介入治疗术后HBV再激活及相关影响因素研究.中国医学前沿杂志(电子版),2014,6(3):27-30.2018-09-26