HBeAg-阴性慢性乙型肝炎病毒感染者停止长期应用阿德福韦酯治疗后获得持续应答和表面抗原清除
目前，对于HBeAg阴性的慢性乙型肝炎病毒感染者停止应用核苷(酸)类似物的长期治疗后的的生化学和病毒学效应所知甚少。我们进行了一项队列观察研究，对33名长期应用（4-5年）阿德福韦酯进行治疗后，血液中检测不到HBV DNA,并且转氨酶水平在正常范围的HBeAg-阴性的慢性乙肝病毒感染者进行随访，所有患者随访5.5年；在随访期的前6个月，每个月检测血浆中ALT的水平，乙肝病毒表面抗原，和HBV DNA定量，之后每3-6个月对上述指标进行检测。在基线水平、治疗结束时及随访期内检测多种指标，以此确定与HBsAg清除相关的因素。在停药后的最初几个月，所有患者都出现了病毒学的复发，其中25人（76%）出现了生化学的复发。在随访期，18人（55%）在停止抗病毒治疗后获得了持续应答（HBV DNA 定量<2000 IU/L,ALT持续在正常范围），在这些个体中，13人（72%）出现了表面抗原的清除。15名患者（45%）出现了病毒学或生化学复发（11人在停药后前18个月内出现，另外4人在停药第三年后出现），之后接受了口服抗病毒药物的再次治疗，这部分个体没有出现肝功能失代偿的指征，只有1名患者出现了HBsAg的清除（6%）。经过多变量分析证实：在治疗前和治疗终点较高水平的ALT，之前未应用干扰素治疗，以及在治疗结束时低水平的乙肝表面抗原滴度与表面抗原的清除密切相关。结论：对于HBeAg-阴性的慢性乙肝病毒感染者，在经过阿德福韦酯进行4-5年的抗病毒治疗后停药是安全有效的，55%的患者可以获得持续应答，39%的患者可以清除乙肝表面抗原。
Sustained Responses and Loss of HBs-Ag in HBeAg-Negative Patients With Chronic Hepatitis B Who Stop Long-term Treatment With Adefovir
BACKGROUND & AIMS:
Little is known about the biochemical and virological effects of stopping long-term nucleos(t)ide analogue therapy for hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B (CHB).
METHODS:
We performed a cohort observational study, following 33 HBeAg-negative patients with CHB, undetectable serum HBV DNA, and normal levels of aminotransferases after long-term (4 or 5 years) treatment with adefovir dipivoxil (ADV). All patients were followed for 5.5 years;follow-up visits included measurements of serum alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), and HBV DNA monthly for the first 6 months and every 3-6 months thereafter. Various factors were measured at baseline, the end of treatment (EOT), and following treatment to identify those associated with clearance of HBsAg.
RESULTS: During the first few months of the postdiscontinuation period, all patients experienced virological and 25 (76%) had biochemical relapse. During the follow-up period, 18 patients (55%) who had discontinued antiviral therapy achieved sustained response (HBV DNA level <2000 IU/L, persistently normal level of ALT). Among these, 13 (72%) cleared HBsAg. Fifteen patients (45%) with virological and/or biochemical relapse were re-treated with oral antiviral agents (11 during the first 18 months and 4 after the third year), without evidence of liver decompensation; only 1 lost HBsAg (6%). Higher pretreatment and EOT levels of ALT, no previous treatment with interferon, and lower level of HBsAg at the EOT were significantly associated with HBsAg clearance based on multivariate analysis
CONCLUSIONS: In HBeAg-negative patients with CHB, it is safe and effective to discontinue ADV therapy after 4 or 5 years; 55% of patients have sustained responses, and 39% of patients lose HBsAg.
目前，对于HBeAg阴性的慢性乙型肝炎病毒感染者停止应用核苷(酸)类似物的长期治疗后的的生化学和病毒学效应所知甚少。我们进行了一项队列观察研究，对33名长期应用（4-5年）阿德福韦酯进行治疗后，血液中检测不到HBV DNA,并且转氨酶水平在正常范围的HBeAg-阴性的慢性乙肝病毒感染者进行随访，所有患者随访5.5年；在随访期的前6个月，每个月检测血浆中ALT的水平，乙肝病毒表面抗原，和HBV DNA定量，之后每3-6个月对上述指标进行检测。在基线水平、治疗结束时及随访期内检测多种指标，以此确定与HBsAg清除相关的因素。在停药后的最初几个月，所有患者都出现了病毒学的复发，其中25人（76%）出现了生化学的复发。在随访期，18人（55%）在停止抗病毒治疗后获得了持续应答（HBV DNA 定量<2000 IU/L,ALT持续在正常范围），在这些个体中，13人（72%）出现了表面抗原的清除。15名患者（45%）出现了病毒学或生化学复发（11人在停药后前18个月内出现，另外4人在停药第三年后出现），之后接受了口服抗病毒药物的再次治疗，这部分个体没有出现肝功能失代偿的指征，只有1名患者出现了HBsAg的清除（6%）。经过多变量分析证实：在治疗前和治疗终点较高水平的ALT，之前未应用干扰素治疗，以及在治疗结束时低水平的乙肝表面抗原滴度与表面抗原的清除密切相关。结论：对于HBeAg-阴性的慢性乙肝病毒感染者，在经过阿德福韦酯进行4-5年的抗病毒治疗后停药是安全有效的，55%的患者可以获得持续应答，39%的患者可以清除乙肝表面抗原。
吉林大学第一医院肝胆胰内科 张明媛 摘译
本文首次发表于[Gastroenterology. 2012 May 31]
本文首次发表于[Gastroenterology. 2012 May 31]
Sustained Responses and Loss of HBs-Ag in HBeAg-Negative Patients With Chronic Hepatitis B Who Stop Long-term Treatment With Adefovir
BACKGROUND & AIMS:
Little is known about the biochemical and virological effects of stopping long-term nucleos(t)ide analogue therapy for hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B (CHB).
METHODS:
We performed a cohort observational study, following 33 HBeAg-negative patients with CHB, undetectable serum HBV DNA, and normal levels of aminotransferases after long-term (4 or 5 years) treatment with adefovir dipivoxil (ADV). All patients were followed for 5.5 years;follow-up visits included measurements of serum alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), and HBV DNA monthly for the first 6 months and every 3-6 months thereafter. Various factors were measured at baseline, the end of treatment (EOT), and following treatment to identify those associated with clearance of HBsAg.
RESULTS: During the first few months of the postdiscontinuation period, all patients experienced virological and 25 (76%) had biochemical relapse. During the follow-up period, 18 patients (55%) who had discontinued antiviral therapy achieved sustained response (HBV DNA level <2000 IU/L, persistently normal level of ALT). Among these, 13 (72%) cleared HBsAg. Fifteen patients (45%) with virological and/or biochemical relapse were re-treated with oral antiviral agents (11 during the first 18 months and 4 after the third year), without evidence of liver decompensation; only 1 lost HBsAg (6%). Higher pretreatment and EOT levels of ALT, no previous treatment with interferon, and lower level of HBsAg at the EOT were significantly associated with HBsAg clearance based on multivariate analysis
CONCLUSIONS: In HBeAg-negative patients with CHB, it is safe and effective to discontinue ADV therapy after 4 or 5 years; 55% of patients have sustained responses, and 39% of patients lose HBsAg.
