慢性HBV感染者拉米夫定治疗与全程管理的临床转归研究
发布时间：2018-11-19 12:57
【摘要】：目的：探讨慢性乙型肝炎患者长期拉米夫定治疗与全程管理的临床转归。 方法：本研究为回顾-前瞻性队列研究。非随机分为两组：1)治疗组：建立慢性乙型病毒性肝炎(CHB)和肝硬化(LC)的LAM抗病毒治疗队列。通过定期随访、监控相关指标,及早发现耐药、复发,及时调整治疗方案,最大限度抑制HBV DNA,稳定肝功能。2)历史对照组：从我科1990年以来门诊和住院患者中筛选HBsAg阳性、ALT或AST异常、HBV-DNA阳性或HBeAg阳性、随访1年的未抗病毒治疗患者共576例,通过倾向评分法(Propensity score method)按1：1匹配出与治疗组一般资料(性别、年龄、基线E抗原、基线诊断)相近的265例作为历史对照组。应用生存分析方法计算两组进入队列至末次访视日期的临床终点事件(肝硬化、肝癌、死亡)累积发生率及年发生率,并用COX风险模型分析影响CHB/LC患者肝硬化、肝癌发生的危险因素。 结果：(1)治疗组265例LAM治疗CHB(79.6%)及LC患者,其中238(89.8%)例初治患者,男性占74.3%,基线E抗原阳性57.7%,平均年龄35.7±12岁。(2)历史对照组265例,CHB(80%),74.3%男性,基线E抗原阳性59.2%,平均年龄35.7±12岁。至末次访视,治疗组和对照组HBV DNA1000copy/ml的患者比例分别为89.1%vs32.1%；两组ALT小于1.3倍正常下限(ULN)的比例分别为89.8%vs18.5%。(3)治疗组中87例(32.8%)曾出现病毒学突破,其中85例为拉米夫定耐药,1、3、5年累积耐药率6.1%、32.1%、38.9%,年均耐药率为10.1%;另外2例为拉米夫定和阿德福韦酯共同耐药；119例(44.9%)停药,72例(60.5%)停药后复发,其中达《2010中国慢乙肝防治指南》停药标准后停药复发的有53.4%(39/73)例,未达标停药后复发率73.3%(33/45)。(4)治疗组211例慢乙肝患者平均随访62±32月,8例发生肝硬化,3例发生肝癌,无死亡患者；对照组212例慢乙肝患者平均随访50±31月,83例发生肝硬化,9例发生肝癌,3例患者死亡；治疗组与对照组慢乙肝患者3年、5年肝硬化累积发生率分别为0.6%vs13.8%,1.5%vs20.8%(P=0.000)；3年、5年肝癌累积发生率分别为0.0%vs2.6%,0.9%vs2.6%(P=0.11).治疗组54例肝硬化患者平均随访5.2年(1.1年~11.6年),7例患者发生肝癌,1例患者死亡；对照组53例肝硬化患者平均随访3.4年(1.0年~16.4年),16例患者发生肝癌,3例发生乙肝相关性死亡；治疗组和对照组3年、5年肝癌概率累计发生率分别为4.2%vs28.3%,10.7%vs39.3%(P=0.000),两组3年、5年累积死亡率分别为0.6%vsl7.3%,2.4%vs22.5%(P=0.047)。(5) COX回归分析显示基线年龄大是发生肝硬化的独立危险因素。基线有肝硬化是发生HCC的独立危险因素。 结论：长期拉米夫定治疗,部分人不可避免会出现耐药、复发,但只要规范的LAM治疗与综合管理相结合,就能够长期最大限度抑制病毒复制,维持患者肝功能长期处于稳定状态,降低肝硬化、肝癌的发生率及HBV相关性死亡率。治疗基线年龄大是发生肝硬化独立危险因素,而基线诊断肝硬化是发生肝癌独立危险因素。
[Abstract]:Objective: to investigate the clinical outcome of long-term lamivudine therapy and whole-course management in patients with chronic hepatitis B. Methods: this study was a retrospective-prospective cohort study. Non-randomized groups were divided into two groups: 1) treatment group: to establish LAM antiviral therapy cohort of chronic hepatitis B (CHB) and liver cirrhosis (LC). Through regular follow-up, monitoring related indicators, early detection of drug resistance, recurrence, timely adjustment of treatment plan, maximum inhibition of HBV DNA, stable liver function. 2) Historical control group: screening positive HBsAg from outpatients and inpatients since 1990. 576 patients with abnormal ALT or AST, HBV-DNA positive or HBeAg positive, were followed up for one year without antiviral therapy. The general data (sex, age, baseline E antigen) of the treatment group (sex, age, baseline E antigen) were matched with the treatment group according to 1:1 by the tendency score method (Propensity score method). Baseline diagnosis) 265 cases were used as historical control group. Survival analysis was used to calculate the cumulative incidence and annual incidence of clinical endpoint events (cirrhosis, liver cancer, death) from the cohort to the date of the last visit. The COX risk model was used to analyze the effects of the two groups on liver cirrhosis in patients with CHB/LC. Risk factors for liver cancer. Results: (1) in the treatment group, 265 cases of CHB (79.6%) and LC were treated with LAM, of which 238 cases (89.8%) were newly treated, male accounted for 74.3%, and the baseline E antigen positive was 57.7%. The average age was 35.7 卤12 years. (2) in the historical control group, there were 265 cases of, CHB (80%, 74.3% male, the baseline E antigen positive was 59.2 years old, the average age was 35.7 卤12 years old. To the last visit, the proportion of HBV DNA1000copy/ml in the treatment group and the control group was 89.1vs32.1; (3) in the treatment group, 87 cases (32.8%) had virological breakthrough, 85 of them were lamivudine resistant, and 1 was 3, the ratio of ALT < 1.3 times normal lower limit (ULN) was 89.8vs18.5. (3) in the treatment group, 87 cases (32.8%) had a virological breakthrough, among which 85 cases were lamivudine resistant. The cumulative drug resistance rate in 5 years was 6.1% and 38.9%, and the average annual drug resistance rate was 10.1%. The other 2 cases were resistant to lamivudine and adefovir ester. One hundred and nineteen cases (44.9%) stopped drug withdrawal and 72 cases (60.5%) recurred after withdrawal. Among them, 53.4% (39 / 73) of the patients reached the standard of stopping drug withdrawal < 2010 Chinese guidelines for the prevention and treatment of chronic hepatitis B. The recurrence rate after discontinuation of drugs was 73.3% (33 / 45). (_ 4) in the treatment group. The mean follow-up of 211 patients with chronic hepatitis B was 62 卤32 months. 8 cases had cirrhosis, 3 cases had liver cancer and no death. In the control group, 212 patients with chronic hepatitis B were followed up for an average of 50 卤31 months, 83 patients developed cirrhosis, 9 patients developed liver cancer and 3 patients died. The cumulative incidence of liver cirrhosis in the treatment group and the control group for 3 years and 5 years was 0.6 vs 13.8and 1.5 vs 20.8% (P < 0.000). The cumulative incidence of liver cancer in 3 years and 5 years was 0. 0 vs 2. 6% and 0. 9% vs 2. 6% (P < 0. 11). In the treatment group, 54 patients with liver cirrhosis were followed up for an average of 5.2 years (1.1 ~ 11.6 years). In the control group, 53 patients with liver cirrhosis were followed up for an average of 3.4 years (1.0 ~ 16.4 years), 16 patients developed liver cancer and 3 patients died of hepatitis B. The cumulative incidence of liver cancer in the treatment group and the control group for 3 years and 5 years were 4.2 vs 28.30.73% (P0. 000), respectively. The cumulative mortality of the two groups for 3 years and 5 years was 0.6vsl7.3%, respectively. COX regression analysis showed that the baseline age was an independent risk factor for cirrhosis. Baseline cirrhosis is an independent risk factor for HCC. Conclusion: drug resistance and relapse will inevitably occur in some people after long-term lamivudine treatment, but as long as the standard LAM therapy is combined with comprehensive management, the virus replication can be restrained as much as possible for a long time. To maintain long-term stable liver function, reduce the incidence of liver cirrhosis, liver cancer and HBV related mortality. The age of treatment baseline is an independent risk factor for liver cirrhosis, while the baseline diagnosis of cirrhosis is an independent risk factor for liver cancer.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.62
本文编号：2342377
[Abstract]:Objective: to investigate the clinical outcome of long-term lamivudine therapy and whole-course management in patients with chronic hepatitis B. Methods: this study was a retrospective-prospective cohort study. Non-randomized groups were divided into two groups: 1) treatment group: to establish LAM antiviral therapy cohort of chronic hepatitis B (CHB) and liver cirrhosis (LC). Through regular follow-up, monitoring related indicators, early detection of drug resistance, recurrence, timely adjustment of treatment plan, maximum inhibition of HBV DNA, stable liver function. 2) Historical control group: screening positive HBsAg from outpatients and inpatients since 1990. 576 patients with abnormal ALT or AST, HBV-DNA positive or HBeAg positive, were followed up for one year without antiviral therapy. The general data (sex, age, baseline E antigen) of the treatment group (sex, age, baseline E antigen) were matched with the treatment group according to 1:1 by the tendency score method (Propensity score method). Baseline diagnosis) 265 cases were used as historical control group. Survival analysis was used to calculate the cumulative incidence and annual incidence of clinical endpoint events (cirrhosis, liver cancer, death) from the cohort to the date of the last visit. The COX risk model was used to analyze the effects of the two groups on liver cirrhosis in patients with CHB/LC. Risk factors for liver cancer. Results: (1) in the treatment group, 265 cases of CHB (79.6%) and LC were treated with LAM, of which 238 cases (89.8%) were newly treated, male accounted for 74.3%, and the baseline E antigen positive was 57.7%. The average age was 35.7 卤12 years. (2) in the historical control group, there were 265 cases of, CHB (80%, 74.3% male, the baseline E antigen positive was 59.2 years old, the average age was 35.7 卤12 years old. To the last visit, the proportion of HBV DNA1000copy/ml in the treatment group and the control group was 89.1vs32.1; (3) in the treatment group, 87 cases (32.8%) had virological breakthrough, 85 of them were lamivudine resistant, and 1 was 3, the ratio of ALT < 1.3 times normal lower limit (ULN) was 89.8vs18.5. (3) in the treatment group, 87 cases (32.8%) had a virological breakthrough, among which 85 cases were lamivudine resistant. The cumulative drug resistance rate in 5 years was 6.1% and 38.9%, and the average annual drug resistance rate was 10.1%. The other 2 cases were resistant to lamivudine and adefovir ester. One hundred and nineteen cases (44.9%) stopped drug withdrawal and 72 cases (60.5%) recurred after withdrawal. Among them, 53.4% (39 / 73) of the patients reached the standard of stopping drug withdrawal < 2010 Chinese guidelines for the prevention and treatment of chronic hepatitis B. The recurrence rate after discontinuation of drugs was 73.3% (33 / 45). (_ 4) in the treatment group. The mean follow-up of 211 patients with chronic hepatitis B was 62 卤32 months. 8 cases had cirrhosis, 3 cases had liver cancer and no death. In the control group, 212 patients with chronic hepatitis B were followed up for an average of 50 卤31 months, 83 patients developed cirrhosis, 9 patients developed liver cancer and 3 patients died. The cumulative incidence of liver cirrhosis in the treatment group and the control group for 3 years and 5 years was 0.6 vs 13.8and 1.5 vs 20.8% (P < 0.000). The cumulative incidence of liver cancer in 3 years and 5 years was 0. 0 vs 2. 6% and 0. 9% vs 2. 6% (P < 0. 11). In the treatment group, 54 patients with liver cirrhosis were followed up for an average of 5.2 years (1.1 ~ 11.6 years). In the control group, 53 patients with liver cirrhosis were followed up for an average of 3.4 years (1.0 ~ 16.4 years), 16 patients developed liver cancer and 3 patients died of hepatitis B. The cumulative incidence of liver cancer in the treatment group and the control group for 3 years and 5 years were 4.2 vs 28.30.73% (P0. 000), respectively. The cumulative mortality of the two groups for 3 years and 5 years was 0.6vsl7.3%, respectively. COX regression analysis showed that the baseline age was an independent risk factor for cirrhosis. Baseline cirrhosis is an independent risk factor for HCC. Conclusion: drug resistance and relapse will inevitably occur in some people after long-term lamivudine treatment, but as long as the standard LAM therapy is combined with comprehensive management, the virus replication can be restrained as much as possible for a long time. To maintain long-term stable liver function, reduce the incidence of liver cirrhosis, liver cancer and HBV related mortality. The age of treatment baseline is an independent risk factor for liver cirrhosis, while the baseline diagnosis of cirrhosis is an independent risk factor for liver cancer.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.62
【参考文献】
相关期刊论文 前1条
1 罗生强,张玲霞,张文谨,蔡少平,高峰;拉米夫定治疗慢性乙型肝炎停药后肝炎复发的临床观察[J];实用肝脏病杂志;2004年04期
，本文编号：2342377
本文链接：https://www.wllwen.com/yixuelunwen/xiaohjib/2342377.html
最近更新
教材专著
