核苷(酸)类似物抗乙型肝炎病毒达到治疗终点标准停药后复发的相关因素分析

目的 探讨影响核苷(酸)类似物(NA)治疗慢性乙型肝炎(CHB)患者达到治疗终点标准(达标)停药后复发的相关因素.方法 CHB患者81例,接受NA抗病毒治疗.拉米夫定(LAM)治疗38例,阿德福韦酯(ADV)25例,恩替卡韦(ETV)12例,LAM+ADV 6例.HBeAg阳性40例,NA初治患者67例,耐药复治14例.达标停药或延长疗程后停药,分别于基线、病毒学应答前每个月、病毒学应答后每3个月、停药后半年内每个月、半年后每2个月检测HBV DNA、HBV血清学标志物和ALT.将性别、年龄、乙型肝炎家族史、基线HBV DNA、基线HBeAg、基线ALT、病毒学应答时间、总疗程(月)、延长疗程(月)、初治或耐药复治、停药时HBsAg水平、药物种类共12个可能影响复发的因素进行单因素、多因素Cox比例风险模型和分层分析,累计复发率采用Kaplan-Meier法计算.结果 81例患者达标停药后,36例患者在1年内复发,占44.4%.初治或耐药复治、乙型肝炎家族史、病毒学应答时间、停药时HBsAg水平分别是影响停药后复发的独立危险因素.耐药复治者复发率高于初治患者(78.6%比37.3%,χ2=7.983,P=0.005),有乙型肝炎家族史的患者复发率高于无乙型肝炎家族史者(64.5%比15.0%,χ2=12.096,P=0.002),病毒学应答发生在3个月内的患者复发率低于发生在3个月后的患者(34.0%比64.3%,χ2=6.823,P=0.009),停药时HBsAg≤150μg/L的患者复发率低于>150μg/L者(27.6%比53.8%,χ2=5.199,P=0.023).结论 耐药复治、有乙型肝炎家族史、病毒学应答时间晚、停药时高水平HBsAg是导致NA治疗停药后复发的主要因素.对此类患者治疗达标后应适当延长疗程,巩固疗效.

Abstract：

Objective To explore the influence factors on hepatitis B virus (HBV) relapse after nucleos(t)ide analogues (NA) withdrawal in the chronic hepatitis B (CHB) patients who met NA cessation criteria. Methods Eighty-one consecutive CHB patients were treated with NA, 38 with lamivudine (LAM), 25 with adefovir dipivoxil (ADV), 12 with entecavir (ETV), 6 with LAM +ADV. Among recruited patients, 40 were hepatitis B virus e antigen (HBeAg) positive, 41 were HBeAg negative, 67 of them were initial treatment, 14 were retreatment due to resistance to NA at baseline. The treatment was discontinued after meeting China therapeutic end-point criteria. HBV DNA, HBV serological markers, alanine aminotransferase (ALT) were measured respectively at baseline, every month before virological response, every 3 months after virological response, every month within first 6 months and every 2 months over 6 months after drugs withdrawal. Twelve probable influence factors on relapse which were sex, age, HBV family history, baseline HBV DNA,baseline HBeAg status, baseline ALT, virological response time, total duration of treatment, duration of additional treatment, the level of hepatitis B virus surface antigen (HBsAg) at cessation therapy,initial treatment or retreatment, drug category were analyzed with univariate, multivariate Cox regression modle and stratified analysis. The cumulative relapse was calculated by the Kaplan-Meier method. Results A total of 36 patients (44. 4%) relapsed within 1 year. Initial treatment or retreatment, HBV family history, virological response time, the level of HBsAg at cessation therapy were independent risk factors. The relapse rate of retreatment was higher than that of initial treatment (78.6% vs 37. 3% , χ2 = 7. 983, P = 0. 005) , those of patients with HBV family history higher than without family history (64. 5% vs 15.0%, χ2 =12. 096,P = 0.002), those of patients obtained virological response within 3 months lower than after 3 months(34. 0% vs 64. 3% , χ2 =6. 823,P=0. 009) , those of patients with HBsAg≤150 μg/L at cessation therapy lower than >150 μg/L(27. 6% vs 53. 8%, χ2=5. 199,P=0. 023). Conclusions Retreatment, HBV family history, later virological response and higher HBsAg level at cessation therapy are risk factors of relapse after NA withdrawal. Such patients should be treated with prolonged duration after meeting end-point criteria to strengthen the efficacy.

Analysis of influence factors on hepatitis B virus relapse after nucleos(t)ide analogues withdrawal in the chronic hepatitis B patients who met nucleos (t) ide analogues cessation criteria

Objective To explore the influence factors on hepatitis B virus (HBV) relapse after nucleos(t)ide analogues (NA) withdrawal in the chronic hepatitis B (CHB) patients who met NA cessation criteria. Methods Eighty-one consecutive CHB patients were treated with NA, 38 with lamivudine (LAM), 25 with adefovir dipivoxil (ADV), 12 with entecavir (ETV), 6 with LAM +ADV. Among recruited patients, 40 were hepatitis B virus e antigen (HBeAg) positive, 41 were HBeAg negative, 67 of them were initial treatment, 14 were retreatment due to resistance to NA at baseline. The treatment was discontinued after meeting China therapeutic end-point criteria. HBV DNA, HBV serological markers, alanine aminotransferase (ALT) were measured respectively at baseline, every month before virological response, every 3 months after virological response, every month within first 6 months and every 2 months over 6 months after drugs withdrawal. Twelve probable influence factors on relapse which were sex, age, HBV family history, baseline HBV DNA,baseline HBeAg status, baseline ALT, virological response time, total duration of treatment, duration of additional treatment, the level of hepatitis B virus surface antigen (HBsAg) at cessation therapy,initial treatment or retreatment, drug category were analyzed with univariate, multivariate Cox regression modle and stratified analysis. The cumulative relapse was calculated by the Kaplan-Meier method. Results A total of 36 patients (44. 4%) relapsed within 1 year. Initial treatment or retreatment, HBV family history, virological response time, the level of HBsAg at cessation therapy were independent risk factors. The relapse rate of retreatment was higher than that of initial treatment (78.6% vs 37. 3% , χ2 = 7. 983, P = 0. 005) , those of patients with HBV family history higher than without family history (64. 5% vs 15.0%, χ2 =12. 096,P = 0.002), those of patients obtained virological response within 3 months lower than after 3 months(34. 0% vs 64. 3% , χ2 =6. 823,P=0. 009) , those of patients with HBsAg≤150 μg/L at cessation therapy lower than >150 μg/L(27. 6% vs 53. 8%, χ2=5. 199,P=0. 023). Conclusions Retreatment, HBV family history, later virological response and higher HBsAg level at cessation therapy are risk factors of relapse after NA withdrawal. Such patients should be treated with prolonged duration after meeting end-point criteria to strengthen the efficacy.