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恩替卡韦抗病毒治疗对乙型肝炎相关肝细胞癌肝动脉化疗栓塞术预后的影响
DOI: 10.3969/j.issn.1001-5256.2021.03.019
利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突，特此声明。
作者贡献声明：何伟猛、何雅婧负责课题设计，资料分析，撰写论文；张植明参与收集数据，修改论文；何伟猛、侯金林负责拟定写作思路，指导撰写文章并最后定稿。
Effect of entecavir antiviral therapy on the prognosis of patients with hepatitis B virus-related hepatocellular carcinoma after transcatheter arterial chemoembolization
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摘要:
目的 探讨恩替卡韦抗病毒治疗对乙型肝炎相关肝细胞癌肝动脉化疗栓塞术(TACE)预后的影响。 方法 选取2011年1月—2018年3月在南方医院肝肿瘤中心首次接受TACE治疗的HCC患者170例，包括恩替卡韦治疗组114例，对照组(未抗病毒治疗)56例。记录治疗前基线的人口学资料，ALT、AST、TBil、Alb、PLT和Child-Pugh分级，HBeAg和HBV DNA水平，AFP、BCLC分期，以及治疗后4~8周的HBV DNA水平，ALT、AST、TBil、Alb和Child-Pugh分级变化和治疗后长期的生存状况。观察患者的短期和长期临床获益(总生存期)。计量资料两组间比较采用t检验或Mann-Whitney U检验；计数资料两组间比较采用χ2检验。对治疗前临床相关指标进行多因素logistic分析，以发现与乙型肝炎再活动的相关危险因素。Kaplan-Meier法分析总生存期的生存曲线，log-rank检验生存曲线间差异性。 结果 恩替卡韦治疗组患者乙型肝炎再活动的发生率与对照组比较无差异(15.79% vs 16.07%，χ2=0.002, P=0.962)。PLT水平在乙型肝炎再活动组与无乙型肝炎再活动组间差异有统计学意义(Z=-2.183, P=0.029)。多因素分析结果显示，HBV DNA水平是乙型肝炎再活动的独立危险因素(HR=1.000，P=0.015)。恩替卡韦组的1、3和5年生存率分别是56.20%、30.30%和13.20%，对照组的1、3和5年生存率分别是60.60%、27.20%和16.30%，两组在总体生存率上差异无统计学意义(χ2= 0.049，P=0.755)。 结论 抗病毒治疗可以抑制乙型肝炎相关HCC患者TACE术后HBV复制，从而减少TACE治疗的肝毒性。 Abstract:Objective To investigate the effect of entecavir (ETV) antiviral therapy on the prognosis of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) receiving transcatheter arterial chemoembolization (TACE). Methods A total of 170 HCC patients who received TACE for the first time in Liver Cancer Center of Nanfang Hospital from January 2011 to March 2018 were enrolled, among whom 114 patients were treated with ETV (ETV treatment group) and 56 patients did not receive antiviral therapy (control group). Baseline demographic data, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), albumin (Alb), platelet count (PLT), Child-Pugh class, HBeAg and HBV DNA levels, alpha-fetoprotein, and BCLC stage were recorded before treatment, and the changes in HBV DNA level, ALT, AST, TBil, Alb, and Child-Pugh class were observed at weeks 4-8 after treatment; long-term survival was also observed after treatment. Short- and long-term clinical benefits (overall survival) were observed for all patients. The t-test or the Mann-Whithey U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. Multivariate logistic regression analyses were performed for related clinical indices before treatment to identify the risk factors for HBV reactivation. The Kaplan-Meier method was used to analyze the survival curves of overall survival, and the log-rank test was used for comparison of survival curves. Results There was no significant difference in the incidence rate of HBV reactivation between the ETV treatment group and the control group (15.79% vs 16.07%, χ2=0.002, P=0.962). The univariate analysis showed that PLT was a risk factor for HBV reactivation (Z=-2.183, P=0.029), and the multivariate analysis showed that HBV DNA level was an independent risk factor for HBV reactivation (hazard ratio =1.000, P=0.015). The 1-, 3-, and 5-year survival rates were 56.20%, 30.30%, and 13.20%, respectively, in the ETV treatment group and 60.60%, 27.20%, and 16.30%, respectively, in the control group. There was no significant difference in overall survival rate between the two groups (χ2=0.049, P=0.755). Conclusion Antiviral therapy can inhibit HBV replication after TACE in patients with HBV-related HCC, thereby reducing the hepatotoxicity of TACE. -
Key words:
- Liver Neoplasms /
- Chemoembolization, Therapeutic /
- Entecavir /
- Prognosis
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表 1 恩替卡韦组和对照组的基线特征比较
指标 恩替卡韦组(n=114) 对照组(n=56) 统计值 P值 男/女(例) 102/12 49/7 χ2=0.147 0.701 年龄(岁) 50.93±10.95 50.45±12.50 t=-0.247 0.806 ALT(U/L) 47.00(30.75~64.93) 41.00(26.25~56.00) Z=-1.658 0.097 AST(U/L) 58.70(40.80~94.08) 50.50(31.25~72.25) Z=-1.933 0.053 TBil(μmol/L) 16.25(11.80~21.80) 15.15(10.08~21.40) Z=-0.922 0.357 Alb(g/L) 36.41±5.58 36.86±5.20 t=0.522 0.603 PT(s) 13.68±1.78 13.46±1.53 t=-0.835 0.405 PLT(×109/L) 153.50(112.75~164.00) 158.50(103.25~217.50) Z=-0.090 0.929 AFP(＜400 ng/ml/≥400 ng/ml, 例) 64/50 36/20 χ2=1.029 0.310 肿瘤直径(cm) 5.50(2.73~9.45) 6.50(3.20~10.45) Z=-1.078 0.281 肿瘤数目(1/2/≥3, 例) 57/7/50 20/5/31 χ2=3.147 0.207 HBV DNA(＜105拷贝/ml/≥105拷贝/ml, 例) 52/62 36/20 χ2=5.243 0.022 HBeAg(阴性/阳性, 例) 87/27 39/17 χ2=0.872 0.350 Child-Pugh分级(A/B, 例) 85/29 40/16 χ2=0.189 0.663 有无门脉癌栓(有/无, 例) 69/45 42/14 χ2=3.472 0.062 BCLC分期(0/A/B/C/D, 例) 9/35/24/33/13 5/17/17/9/8 χ2=4.171 0.383 
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表 2 乙型肝炎再活动的单因素分析
指标 乙型肝炎再活动(n=27) 无乙型肝炎再活动(n=143) 统计值 P值 男/女(例) 23/4 128/15 χ2=0.428 0.513 年龄(岁) 49.19±10.35 51.07±11.65 t=0.784 0.434 ALT(U/L) 45.00(30.50~60.80) 44.00(28.00~61.10) Z=-0.303 0.762 AST(U/L) 60.00(43.00~115.00) 53.00(37.00~86.50) Z=-0.981 0.327 TBil(μmol/L) 17.80(12.20~24.50) 15.10(11.35~21.40) Z=-1.328 0.184 Alb(g/L) 36.15±5.36 36.64±5.48 t=0.422 0.674 PT(s) 13.73±1.65 13.58±1.72 t=-0.428 0.670 PLT(×109/L) 155.00(118.50~210.50) 155.00(106.00~222.00) Z=-2.183 0.029 AFP(＜400/≥400 ng/ml, 例) 16/11 85/58 χ2=0.000 0.986 肿瘤直径(cm) 6.80(2.90~11.50) 5.90(3.00~9.45) Z=-1.759 0.079 肿瘤数目(1/2/≥3，个) 11/0/16 66/12/65 χ2=3.321 0.190 HBV DNA(＜105拷贝/ml/≥105拷贝/ml，例) 14/13 74/69 χ2=0.000 0.992 HBeAg(阴性/阳性, 例) 19/8 107/36 χ2=0.235 0.628 Child-Pugh(A/B，例) 19/8 106/37 χ2=0.165 0.685 有无门脉癌栓(有/无，例) 11/16 51/92 χ2=0.253 0.615 BCLC分期(0/A/B/C/D，例) 1/6/10/6/4 8/46/33/37/19 χ2=2.797 0.592 抗病毒治疗(是/否, 例) 18/9 96/47 χ2=0.002 0.962
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表 3 乙型肝炎再活动的多因素分析
指标 B值 SE Wald HR 95%CI P值 PLT 0.002 0.003 0.812 0.998 0.993~1.003 0.368 肿瘤直径 0.077 0.009 2.431 1.080 0.980~1.189 0.119 抗病毒治疗 0.305 0.455 0.449 1.356 0.556~3.308 0.503 HBV DNA 0.000 0.000 5.915 1.000 1.000~1.000 0.015 HBeAg 0.866 0.480 3.255 0.421 0.164~1.078 0.071
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[1] BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424. DOI: 10.3322/caac.21492 [2] VILLANUEVA A. Hepatocellular carcinoma[J]. N Engl J Med, 2019, 380(15): 1450-1462. DOI: 10.1056/NEJMra1713263 [3] VERSLYPE C, ROSMORDUC O, ROUGIER P, et al. Hepatocellular carcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up[J]. Ann Oncol, 2012, 23(Suppl 7): vii41-48. http://www.biomedcentral.com/pubmed/22997452 [4] OMATA M, CHENG AL, KOKUDO N, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: A 2017 update[J]. Hepatol Int, 2017, 11(4): 317-370. DOI: 10.1007/s12072-017-9799-9 [5] WANG K, JIANG G, JIA Z, et al. Effects of transarterial chemoembolization combined with antiviral therapy on HBV reactivation and liver function in HBV-related hepatocellular carcinoma patients with HBV-DNA negative[J]. Medicine (Baltimore), 2018, 97(22): e10940. DOI: 10.1097/MD.0000000000010940 [6] LIN XJ, LAO XM, SHI M, et al. Changes of HBV DNA after chemoembolization for hepatocellular carcinoma and the efficacy of antiviral treatment[J]. Dig Dis Sci, 2016, 61(9): 2465-2476. DOI: 10.1007/s10620-016-4167-5 [7] PIETRO L, KOSH A THOMAS B, et al. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection[J]. J Hepatol, 2017, 67(2): 370-398. DOI: 10.1016/j.jhep.2017.03.021 [8] Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B (version 2019)[J]. J Clin Hepatol, 2019, 35(12): 2648-2669. (in Chinese) DOI: 10.3969/j.issn.1001-5256.2019.12.007中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007 [9] LIU WP, XIAO XB, XUE M, et al. Prophylactic use of entecavir for lymphoma patients with past hepatitis B virus infection: A randomized controlled trial[J]. Clin Lymphoma Myeloma Leuk, 2019, 19(2): 103-108. DOI: 10.1016/j.clml.2018.11.008 [10] National Comprehensive Cancer Network.NCCN clinical practice guidelines in oncology: Hepatobiliary cancers (2012)[EB/OL].https://www.nccn.org/. [11] YEO W, JOHNSON PJ. Diagnosis, prevention and management of hepatitis B virus reactivation during anticancer therapy[J]. Hepatology, 2006, 43(2): 209-220. DOI: 10.1002/hep.21051/full [12] LAO XM, LUO G, YE LT, et al. Effects of antiviral therapy on hepatitis B virus reactivation and liver function after resection or chemoembolization for hepatocellular carcinoma[J]. Liver Int, 2013, 33(4): 595-604. DOI: 10.1111/liv.12112 [13] YU LH, LI N, SHI J, et al. Does anti-HBV therapy benefit the prognosis of HBV-related hepatocellular carcinoma following hepatectomy?[J]. Ann Surg Oncol, 2014, 21(3): 1010-1015. DOI: 10.1245/s10434-013-3320-z [14] KUSUMOTO S, ARCAINI L, HONG X, et al. Risk of HBV reactivation in patients with B-cell lymphomas receiving obinutuzumab or rituximab immunochemotherapy[J]. Blood, 2019, 133(2): 137-146. DOI: 10.1182/blood-2018-04-848044 [15] PARK JW, PARK KW, CHO SH, et al. Risk of hepatitis B exacerbation is low after transcatheter arterial chemoembolization therapy for patients with HBV-related hepatocellular carcinoma: Report of a prospective study[J]. Am J Gastroenterol, 2005, 100(10): 2194-2200. DOI: 10.1111/j.1572-0241.2005.00232.x [16] LIAO Y, WANG B, HUANG ZL, et al. Increased circulating Th17 cells after transarterial chemoembolization correlate with improved survival in stage Ⅲ hepatocellular carcinoma: A prospective study[J]. PLoS One, 2013, 8(4): e60444. DOI: 10.1371/journal.pone.0060444 [17] LAO XM, LUO G, YE LT, et al. Effects of antiviral therapy on hepatitis B virus reactivation and liver function after resection or chemoembolization for hepatocellular carcinoma[J]. Liver Int, 2013, 33(4): 595-604. DOI: 10.1111/liv.12112 [18] JIANG E, SHANGGUAN AJ, CHEN S, et al. The progress and prospects of routine prophylactic antiviral treatment in hepatitis B-related hepatocellular carcinoma[J]. Cancer Lett, 2016, 379(2): 262-267. DOI: 10.1016/j.canlet.2015.07.016 [19] HEIMBACH JK, KULIK LM, FINN RS, et al, AASLD guidelines for the treatment of hepatocellular carcinoma[J]. Hepatology, 2018, 67(1): 358-380. DOI: 10.1002/hep.29086 -
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