慢性HBV感染的核苷类药物联合抗病毒治疗及相关研究

发布时间：2018-03-31 22:11

本文选题：慢性HBV感染　切入点：抗病毒治疗　出处：《兰州大学》2014年硕士论文

【摘要】：背景：慢性乙型肝炎病毒(hepatitis B virus, HBV)感染呈世界性流行,且我国为乙肝大国。目前抗病毒治疗是慢性HBV感染的关键治疗和最有效治疗,可抑制病毒复制、促进肝脏病变恢复、减少或延缓并发症的发生及提高患者生活质量。目前最常用抗病毒药物为核苷类药物。由于核苷类药物抗病毒治疗时间长、社会负担重,优化其治疗方案是临床亟待解决的课题。近年来,采用联合治疗及个体化治疗的策略已逐渐成为国际共识。慢性HBV感染可导致肝硬化、肝细胞癌(hepatocellular carcinoma, HCC)等严重并发症,严重威胁人类健康,而肝纤维化是慢性HBV感染走向肝硬化的必经途径,对其进行监测、早期诊治可以有效阻止肝硬化等并发症的发生,近几年无创诊断肝纤维化成为研究热点。我国90%以上的HCC是由HBV感染引起,其起病隐匿、进展迅速、发现时多已失去手术机会及预后差,HBV致HCC发病机理、抗病毒阻止肝癌发生的疗效等仍在探讨中。目的：系统评价替比夫定联合阿德福韦酯治疗慢性乙型肝炎(chronic hepatitis B, CHB)的疗效及安全性,为临床实践与研究提供参考；了解在慢性HBV感染病程中监测肝纤维化的意义及瞬时弹性成像诊断肝纤维化的最新研究进展；探讨慢性HBV感染致HCC的主要发病机理和临床诊治,及慢性HBV感染抗病毒治疗阻止肝癌发生的疗效与影响因素,为HCC的预防、早期发现及诊疗等作出一定贡献。方法：应用系统评价方法,计算机检索Cochrane Library、PubMed、EMBASE、 Web of Science、CBM、CNKI、WANFANG八大数据库,同时辅以其他检索,收集所有相关的随机对照试验(randomized controlled trial, RCT);由两位评价员按照研究计划书进行文献筛选和资料提取,并对纳入文献进行质量评价后,使用RevMan5.1软件进行Meta分析。采用综述方法研究慢性HBV感染相关性肝纤维化的监测意义及肝纤维化、肝癌的有关诊治进展。回顾性分析兰州大学第一医院东岗院区肝病中心在2012年10月-2013年6月收治的6例慢性HBV感染者在规范抗病毒治疗期间出现HCC的相关临床资料。结果：系统评价共纳入11篇RCT,包括1010例患者。试验组采用替比夫定联合阿德福韦酯治疗,对照组采用单药替比夫定或单药阿德福韦酯治疗。Meta分析结果显示：除试验组对比单药替比夫定组的48周ALT复常率外,在12周、24周和48周的HBV DNA阴转率、HBeAg阴转率以及ALT复常率等各项指标方面,试验组均优于单药替比夫定组或单药阿德福韦酯组(P0.05)；定性分析结果显示试验组的耐药发生率最低,且试验组并不增加药物不良反应。对慢性HBV感染者进行肝纤维化监测、评估并及时给予干预措施使其逆转可有效阻止肝硬化等并发症的发生；瞬时弹性成像是诊断肝纤维化的一种新型、快速方便、无创、经济、可重复的诊断技术。HBV致HCC的发病机理非常复杂,目前尚未完全阐明,主要包括直接作用机制及间接作用机制；临床确诊HCC主要采用血清学和影像学方法；HBV相关性HCC的抗病毒治疗是最基本的病因治疗。回顾性分析结果示：纳入6例慢性HBV感染者,其中慢性肝炎2例,肝硬化4例；HBeAg阴性5例；3例合并糖尿病;经抗病毒治疗后病毒载量均处于低度复制或不可测状态。结论：核苷类药物联合疗法治疗CHB能提高患者治疗的有效性,且安全性较好；受限于纳入研究的数量和质量,上述结论尚需今后开展更多大样本、高质量的RCT加以验证。在慢性HBV感染病程中监测肝纤维化具有重要意义,而瞬时弹性成像是目前诊断肝纤维化的主要无创诊断方法。明确HBV相关性HCC发病机理、熟练掌握HCC的临床诊断方法对其预防、早期发现及诊疗具有重要意义。经抗病毒治疗不能完全消除HCC发生的风险,病毒载量、HBeAg阴性、糖尿病、肝硬化等可能是HCC发生的危险因素。
[Abstract]:Background : Chronic hepatitis B virus ( HBV ) infection is a worldwide epidemic , and our country is a major hepatitis B . At present , antiviral therapy is the key treatment and most effective treatment of chronic HBV infection . It can inhibit the replication of virus , promote the recovery of liver disease , reduce or delay the occurrence of complications and improve the quality of life of patients . In recent years , the most commonly used antiviral drugs are nucleoside medicaments . In recent years , the treatment of chronic HBV can lead to serious complications such as liver cirrhosis and hepatocellular carcinoma ( HCC ) .

Objective : To evaluate the efficacy and safety of tebivudine combined with adefovir in the treatment of chronic hepatitis B ( chronic hepatitis B ) , and provide a reference for clinical practice and research .
To investigate the significance of monitoring hepatic fibrosis in the course of chronic HBV infection and the latest development of transient elastography in the diagnosis of hepatic fibrosis ;
To investigate the main pathogenesis and clinical diagnosis and treatment of HCC caused by chronic HBV infection , and the therapeutic effect and influencing factors of chronic HBV infection in the prevention and treatment of HCC , and to make a certain contribution to prevention , early detection and diagnosis and treatment of HCC .

Methods : A systematic evaluation method was used to search for all relevant randomized controlled trials ( RCTs ) by computer . All the relevant randomized controlled trials ( RCTs ) were collected by computer . All the relevant randomized controlled trials ( RCTs ) were collected by two reviewers according to the study plan . After the quality evaluation of the literatures , the clinical data of 6 cases of chronic HBV infection related to liver fibrosis were analyzed retrospectively .

Results : 11 RCTs were included in the system evaluation , including 1010 patients . The test group was treated with tebivudine and adefovir divecuride . The results of Meta - analysis showed that the test group was superior to the single - dose tibivudine group or the single - agent adefovir difester group ( P0.05 ) .
The results of qualitative analysis showed that the drug resistance of the test group was the lowest , and the trial group did not increase the adverse drug reactions .

To monitor the liver fibrosis in patients with chronic HBV infection , assess and timely give the intervention measures to prevent the occurrence of complications such as liver cirrhosis effectively ;
Transient elastography is a new , rapid , non - invasive , economical and reproducible diagnostic technique for the diagnosis of liver fibrosis . The pathogenesis of HBV - induced HCC is very complex and is not yet fully elucidated , including the direct acting mechanism and the indirect action mechanism .
The clinical diagnosis of HCC mainly adopts serological and imaging methods .
The antiviral therapy of HBV - related HCC is the most basic cause of treatment .

The results of the retrospective analysis showed that 6 cases of chronic HBV infection were included , including 2 cases of chronic hepatitis and 4 cases of cirrhosis ;
HBeAg negative in 5 cases ;
3 cases with diabetes mellitus ; viral load after anti - viral treatment was in low - degree or non - measurable state .

Conclusion : The combination therapy of nucleoside drugs can improve the effectiveness and safety of the patients .
It is important to monitor liver fibrosis in the course of chronic HBV infection , and transient elastography is the main noninvasive method for diagnosis of liver fibrosis .

【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.62

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