拉米夫定治疗慢性乙型肝炎的耐药分析及处理  

Lamivudine-resistant analysis and management for chronic hepatitis B patients with initial iamivudine therapy

作　　者：徐辉[1] 陈杨[1] 何伶俐[1] 雷秉钧[1] 雷学忠[1] 

机构地区：[1]四川大学华西医院感染性疾病中心生物治疗国家重点实验室感染性疾病研究室,成都610041

出　　处：《中华肝脏病杂志》2011年第6期427-430,共4页Chinese Journal of Hepatology

摘　　要：目的探讨拉米夫定长期治疗慢性乙型肝炎（CHB）患者的耐药因素及其耐药后处理措施，为合理应用拉米夫定提供依据。方法2001年9月2010年1月应用拉米夫定初治的CHB患者383例，治疗观察满1年。其中发生病毒学突破或反弹患者129例，分为换用阿德福韦酯治疗组和加用阿德福韦酯治疗组。疗效评估包括血清HBV病毒学、血清HBV免疫学、血生物化学应答，观察时间至少1年。定性资料采用xz检验，反弹时间分布关系用生存分析曲线描述。结果383例CHB患者3个月、半年、l、2、3年以及3年后HBVDNA阴转率分别为40．7％、55．6％、59．5％、56．7％、55．9％和55．6％。HBeAg血清学转换62例，占22．6％。原发耐药12例，突破反弹129例，累计耐药率为36．8％，累计反弹率为34．8％。基线高病毒载量、基线ALT水平〈2倍正常值上限、治疗24周时的病毒学低应答，与较高的反弹率相关，x。值分别为35．716、8．728和43．534，JD值均〈0．01。病毒学突破反弹发生在1年半内112例（86．8％），2年内123例（95．3％），5年以后未再发现病毒学突破反弹患者。129例病毒学突破反弹的患者予以换用阿德福韦酯或加用阿德福韦酯继续治疗，换药和加药后的再次阴转率分别为22．7％（15／66）和58．7％（37／63），病毒学应答率分别为59．1％（39／66）和87．3％（55／63），X^2值分别为17．364和12．975，JD值均〈0．叭，差异有统计学意义。结论拉米夫定初始治疗的CHB患者，耐药反弹主要发生在2年以内，对于拉米夫定耐药的CHB患者，拉米夫定联合阿德福韦酯比单用阿德福韦酯治疗可取得更好的疗效。Objective To study the factors influencing the long-term usage of lamivudine （LAM） in chronic hepatitis B （CHB） patients and the management after drug^resistance. Methods 383 cases of naive CHB patients in our outpatient clinic were treated with lamivudine （100 mg/d） and followed up for at least over 1 year from 2001 to 2010. 129 cases encountered lamivudine-resistance and were then divided into two groups： patients in group A were switched to adefovir dipivoxil （ADV） alternative treatment and those patients in group B were added with ADV for continuous treatment. Efficacy assessment factors included serum HBV markers, HBV DNA, ALT, AFP and other biochemical indicators. Results Among the 383 cases, patients with HBV DNA negative conversion （PCR below test line） at 3 months, 6 months, 1 year, 2 years, 3 years and 〉 3 years after initial treatment were respectively 156 cases （40.7%）, 213 cases （55.6%）, 228 cases （59.5%）, 217cases （56.7%）, 214 cases （55.9%） and 213 cases （55.6%）. HBeAg/HBeAb seroconversion occurred in 62 cases （22.6%）. 12 cases were found with primary LAM resistance, 129 cases with HBV break- through and rebound, the cumulative resistance rate was 36.8% and the cumulative rebound rate was 34.8%.High baseline viral load, baseline ALT levels 〈 2 ULN, Lower virologic response rate at week 24 were associated with a higher rebound rate （ x2 is 35.716, 8.728, 43.534, respectively, all with P 〈 0.01）.Viral breakthrough and rebound occurred in 112 patients （86.8%） within 1 year and a haf, 123 patients （95.3%） occurred at the end of 2 years and no patient with viral breakthrough and rebound after 5 years. For the patients with viral rebound in group A and group B, the rates of HBV DNA loss were 22.7% （15/66） and 58.7% （37/63） respectively, and the viral response rates were 59.1% （39/66） and 87.3% （52/63） respectively, with x^2 values equaled 17.364 and 12.975 respectively （P 〈 0.01）. Conclusion For the chronic hepatitis

关 键 词：肝炎 乙型 慢性 治疗 拉米夫定 药物耐受 病毒 阿德福韦酯 

分 类 号：R512.62[医药卫生—内科学]