循证医学作业 (1)

循证医学作业 (1) 循证医学作业 班级:2010级3班 姓名:梁云宇 学号:201050321 一:疾病案例 乙型 慢性 中度”，患者，男性，33岁，已婚。1年前诊断为“病毒性肝炎 当时肝功能ALT135U/L,AST126U/L,乙肝三系表面抗原、E抗原、核心抗体三项阳性，HBV DNA2.63x10e6拷贝/毫升。服用拉米夫定片100mg qd抗乙肝病毒治疗。定期复肝功能、乙肝三系、HBV DNA 等，近一年来肝功能ALT58-130U/L、AST40-60U/L, HBV DNA1.34 x10e4-2.68 x10e5拷贝/毫升。昨日查肝功能ALT126U/L, AST60U/L,乙肝三系表面抗原、E抗原、核心抗体三项阳性.B超:肝光点细密，胆囊壁毛糙，甲肝丙肝丁肝戊肝等病毒抗体全阴性。自觉乏力，纳差。体格检查:巩膜未见黄染，颈部见2颗蜘蛛痣，腹部平软，无压痛及反跳痛，肝脏脾脏未触及，墨菲征阴性，移动性浊音阴性。否认服用拉米夫定以外的药物。不饮酒，不吸烟。无其他不良嗜好。母亲为慢性乙肝患者。 初步诊断:病毒性肝炎 乙型 慢性 中度 诊断评估: ，现肝功能异常，HBV DNA阳性，辅助患者原有乙肝家族史，慢性乙肝病史1年 检查排除了脂肪肝和其他常见的病毒性肝炎，从病史排除药物性肝炎等情况。故初步诊断病毒性肝炎 乙型 慢性 中度。 提出问题: 二:PICO与 P 肝功能反复异常 HBV DNA持续阳性 I 拉米夫定 C 无 O 治疗结果好转 患者服用拉米夫定治疗，病情一直未完全稳定。肝功能反复异常，HBV DNA持续阳性。拉米夫定抗病毒治疗效果差。下一步如何治疗, 三:证据检索与评价 文献检索资源:PubMed; Cochrane library 检索词(chronic hepatitis B)and (Lamivudine) and (refractory) 检索结果 找到2关系最为密切的文献 第一篇 [A clinical study of adefovir dipivoxil in treating lamivudine refractory HBeAg-positive chronic hepatitis B] Zhao H, Zhang YX, Chen XY, Wang L, Tang XP, Si CW Year: 2007 Record The Cochrane Central Register of Controlled Trials (CENTRAL) 2009 Issue 1 Copyright ? 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Title [A clinical study of adefovir dipivoxil in treating lamivudine refractory HBeAg-positive chronic hepatitis B] Links Export Central Citation Author(s) Zhao H, Zhang YX, Chen XY, Wang L, Tang XP, Si CW Source Zhonghua nei ke za zhi [Chinese journal of internal medicine] Date of Publication 2007 Apr Volume 46 Issue 4 Pages 294-7 Abstract OBJECTIVE: To evaluate the efficacy and safety of adefovir dipivoxil (ADV) in treating patients with lamivudine (LAM) refractory HBeAg-positive chronic hepatitis B. METHODS: It is a randomized, double-blind, placebo-controlled, multicenter study. 226 eligible patients with HBeAg-positive chronic hepatitis B were randomized (randomization ratio was 2:1) into two groups. One group received ADV 10 mg/d and LAM 100 mg/d for 12 weeks and followed by ADV 10 mg/d for 36 weeks (ADV + LAM-->ADV group); the other received placebo and LAM 100 mg/d for 12 weeks and followed by ADV 10 mg/d for 36 weeks (placebo + LAM-->ADV group). The primary efficacy measure was virological response. The secondary efficacy measure was serological response (HBeAg loss rate and HBeAg seroconversion rate) and ALT normalization rate. RESULTS: After 12 weeks of therapy, mean reduction of HBV DNA level, the percentage of patients with HBV DNA lower than 5 l g copies/ml and the percentage of patients with HBV DNA level decrease of more than 2 l g copies/ml in patients of ADV + LAM-->ADV group were significantly higher than those in patients of placebo + LAM-->ADV group (2.69 lg copies/ml vs. 1.06 lg copies/ml, 92.7% vs. 33.3%, 78.1% vs. 27.8%), all the P values were 0.00. HBV DNA undetectable (<3l g copies/ml) rate and serological response (HBeAg loss rate and HBeAg seroconversion rate) in patients of ADV + LAM-->ADV group was slightly higher than those in patients of placebo + LAM-->ADV group (12.2% vs 5.6%, 5.1% vs 0, 4.9% vs 0), but did not reach statistical significance. Much more patients in both treatment arms achieved virological response, serological response and ALT normalization after another 36 weeks of therapy. The overall safety profile of ADV was similar to that of placebo. rtN236T and rtA181V mutation was not found in this 48-week study. CONCLUSION: ADV is an effective and well-tolerated treatment option for patients with LAM refractory HBeAg-positive chronic hepatitis B. Medical Subject Adenine [*analogs & derivatives; therapeutic use]; Adolescent; Headings (MeSH) Antiviral Agents [therapeutic use]; DNA, Viral [blood]; Drug Resistance, Viral; Hepatitis B, Chronic [*drug therapy]; Hepatitis B e Antigens [blood]; Hepatitis B virus [*drug effects; genetics; immunology]; Lamivudine [therapeutic use]; Phosphonic Acids [*therapeutic use]; Reverse Transcriptase Inhibitors [therapeutic use]; Treatment Outcome MeSH check words Adult; Aged; Female; Humans; Male; Middle Aged Correspondence Address Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China. Accession Number PUBMED 17637268 Language Chi Publication Type English Abstract; Journal Article; Multicenter Study; Randomized Controlled Trial ID CN-00636872 第二篇 Entecavir for treatment of lamivudine-refractory, HBeAg-positive chronic hepatitis B. Sherman M, Yurdaydin C, Sollano J, Silva M, Liaw YF, Cianciara J, Boron-Kaczmarska A, Martin P, Goodman Z, Colonno R, Cross A, Denisky G, Kreter B, Hindes R; AI463026 BEHoLD Study Group. Gastroenterology. 2006 Jun;130(7):2039-49. PMID: 16762627 [PubMed - indexed for MEDLINE] Related Articles Entecavir for treatment of lamivudine-refractory, HBeAg-positive chronic hepatitis B. Sherman M, Yurdaydin C, Sollano J, Silva M, Liaw YF, Cianciara J, Boron-Kaczmarska A, Martin P, Goodman Z, Colonno R, Cross A, Denisky G, Kreter B, Hindes R; AI463026 BEHoLD Study Group. Department of Medicine, Toronto General Hospital, Toronto, Ontario, Canada. Dr.Morris.sherman@uhn.on.ca BACKGROUND & AIMS: Lamivudine treatment is associated with frequent development of resistant hepatitis B virus (HBV) and loss of treatment benefit. In preclinical and phase II studies, entecavir demonstrated potent antiviral activity against lamivudine-resistant HBV. METHODS: In this phase III, double-blind trial, hepatitis B e antigen-positive patients who were refractory to lamivudine therapy (persistent viremia or documented YMDD mutations while receiving lamivudine) were randomized to switch to entecavir 1 mg daily (n = 141) or continue lamivudine 100 mg daily (n = 145) for a minimum of 52 weeks. Two coprimary end points were assessed at 48 weeks: histologic improvement and a composite end point (HBV branched DNA <0.7 MEq/mL and alanine aminotransferase [ALT] <1.25 times the upper limit of normal). RESULTS: Histologic improvement occurred in 55% (68/124) of entecavir-treated vs 28% (32/116) of lamivudine-treated patients (P < .0001). More patients on entecavir than lamivudine achieved the composite end point: 55% (77/141) vs 4% (6/145), respectively (P < .0001). Mean change from baseline in HBV DNA was -5.11 log(10) copies/mL for entecavir-treated patients and -0.48 log(10) copies/mL for lamivudine-treated patients (P < .0001). Virologic rebound because of entecavir resistance substitutions occurred in 2 of 141 of entecavir-treated patients, and genotypic evidence of resistance was detected in 10 patients. The safety profile of entecavir was comparable to lamivudine with fewer ALT flares on treatment. CONCLUSIONS: In patients with lamivudine-refractory chronic hepatitis B, switching to entecavir provides superior histologic improvement, viral load reduction, and ALT normalization compared with continuing lamivudine, with a comparable adverse event profile. PMID: 16762627 [PubMed - indexed for MEDLINE] 证据级别:A级(研究为RCT试验) 回答问题 治疗有两种选择:1，在拉米夫定片100mg qd治疗基础上加用阿德福韦酯 10mg qd 2,停用拉米夫定片，改用恩替卡韦片1.0mg qd治疗。 结合病人情况，治疗方案如下 患者经济条件一般，难以承担恩替卡韦片每日76元的费用，最后选用在拉米夫 定片100mg qd治疗基础上加用阿德福韦酯10mg qd的方案。并嘱患者定期门诊 复诊。 五，小结: 收获:(1) 对于本门课程有了较深刻的了解，并掌握一些相关知识， 认识到了通过循证实践能获得最佳的研究证据用于决策 患者的研究治疗方案，有利于医疗卫生质量的改善和提 高。 (2) 通过检索，较好的掌握了检索的过程及步骤，。以及如 何评价文献。为以后的工作积累了部分经验同时奠定了 基础。 (3) 通过本次检索，激起了我对循证医学的浓厚兴趣，加深 了我对相关知识的理解与掌握。