恩替卡韦治疗高ALT水平HBeAg阳性慢性乙型肝炎疗效观察

目的观察恩替卡韦治疗高ALT水平HBeAg阳性慢性乙型肝炎（CHB）患者的疗效。方法 60例HBeAg阳性的CHB患者以ALT为依据分为低ALT组（ALT在2倍ULN与10倍之间）和高ALT组（ALT在10倍ULN与20倍之间）,给予恩替卡韦0.5mg/d,观者治疗48周时的应答情况（HBV DNA阴转率,HBeAg/抗-HBe血清转换率,HBsAg/抗-HBs血清转换率和ALT复常率）。结果治疗48周时,高ALT组HBV DNA阴转率为95.0%,低ALT组为75.0%,差异有统计学意义（P=0.0225）;低ALT组HBeAg阴转率、HBeAg血清学转换率、HBsAg阴转率、HBsAg血清学转换率依次为25.0%、25.0%、0.0%、0.0%,均明显低于高ALT组的55.0%、45.0%、15.0%、15.0%,差异有统计学意义（P=0.0184,0.0302,0.0015,0.0012）;高ALT组中有3例出现HBsAg阴转,3例出现了HBsAb;低ALT组中没有出现HBsAg阴转及血清学转换。48周时两组患者ALT复常率、病毒学反弹、对恩替卡韦耐药及药物不良反应水平相似。结论高水平ALT是恩替卡韦治疗应答较好的预测因子。     

恩替卡韦联合苦参素治疗HBeAg阳性慢性乙型肝炎患者疗效研究

目的 探讨恩替卡韦联合苦参素治疗HBeAg阳性慢性乙型肝炎(CHB)患者的疗效及对淋巴细胞亚群的影响。方法 2019年3月～2021年3月我院收治的96例HBeAg阳性CHB患者被随机分为对照组48例和观察组48例,分别给予恩替卡韦或恩替卡韦联合苦参素胶囊治疗,两组治疗观察48 w。采用PCR法检测血清HBV DNA载量,采用ELISA法检测血清HBeAg,使用流式细胞仪检测外周血T淋巴细胞亚群,采用ELISA法检测血清IL-10、IL-17和IL-23水平。结果 在治疗48 w末,观察组血清AST和ALT分别为(31.2±4.7)U/L和(38.7±9.4)UL,显著低于对照组【分别为(46.3±6.8)U/L和(66.1±13.6)U/L,P<0.05】;观察组血清ALT复常率为83.3%,显著高于对照组的64.6%(P<0.05);观察组外周血CD3⁺、CD4⁺细胞百分比和CD4⁺/CD8⁺细胞比值分别为(73.4±8.1)%、(47.2±6.1)%和(1.9±0.6),均显著高于...     

恩替卡韦治疗慢性乙型肝炎患者血清HBsAg变化与病毒学应答的相关性研究

目的 探讨应用恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者血清HBsAg的变化以及与病毒学应答之间的关系。方法 2014年9月~2015年12月我院诊治的142例HBeAg阳性慢性乙型肝炎患者接受恩替卡韦治疗,观察96周。采用荧光定量PCR 法检测血清HBV DNA,采用酶联免疫吸附法检测HBV 标记物。结果 在治疗24周末,87例患者获得完全病毒学应答,55例获得部分病毒学应答;完全病毒学应答组血清HBeAg 水平为（204.5±64.2）S/CO,显著低于部分应答组的【（226.2±70.5） S/CO,P<0.05】,HBsAg 水平为（2.9±0.2） lg IU/mL,显著低于部分应答组的【（3.4±0.3） lg IU/mL,P<0.05】;在治疗48周末,两组血清HBeAg和HBsAg水平无显著性相差（P>0.05）;在治疗96周末,两组血清HBsAg水平无显著性差异（P>0.05）,但完全病毒学应答组血清HBV DNA水平为（1.1±0.9） lg IU/mL,显著低于部分应答组的【（4.3±0.8） lg IU/mL,P<0.05】。结论 恩替卡韦治疗的HBeAg阳性慢性乙型肝炎患者血清HBeAg 和HBsAg水平变化不显著,对继续治疗的效果也没有预测意义,因此应对不完全应答的患者早日更换治疗方案。     

恩替卡韦联合双环醇治疗HBeAg阳性慢性乙型肝炎的疗效分析

目的 研究恩替卡韦联合双环醇片治疗HBeAg阳性慢性乙型肝炎患者的疗效和安全性.方法 选择未应用其他抗病毒药物的HBeAg阳性慢性乙型肝炎患者113例,并将其随机分成两组.试验组57例,每日口服恩替卡韦0.5 mg,同时每日服用双环醇片75 mg;对照组56例,仅给予口服恩替卡韦每日0.5 mg,两组均连续用药104周,观察治疗前后血清丙氨酸氨基转移酶(ALT)水平及病毒学指标的改变.结果 两组患者血清ALT均明显下降,试验组更为显著(P＜0.01).治疗12周时,两组患者HBeAg转阴率及血清学转换方面比较,差异均无统计学意义(P＞0.05).随治疗时间延长,在治疗24、52、104周各时间点,试验组HBeAg转阴率及血清学转换均优于对照组,两组比较差异有统计学意义(P＜0.05).两组HBV DNA水平均出现明显下降,但各治疗时间点HBV DNA下降水平及检测不到比率比较,差异无统计学意义(P＞0.05).治疗52周时,试验组和对照组各出现1例和2例耐药,耐药率分别为1.75％和3.57％,两组比较差异无统计学意义(P＞0.05);治疗104周时,试验组耐药1例,对照组耐药3例,耐药率分别为1.75％和5.36％,两组比较差异有统计学意义(P＜0.05).2组患者均未发生与研究药物相关的不良反应.结论 恩替卡韦与双环醇片联合应用治疗HBeAg阳性慢性乙型肝炎,在肝功能及病毒学方面均取得较好疗效且安全.     

恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者疗效和安全性评价

据世界卫生组织报道,全球约20亿人曾感染过HBV,其中3.5亿人为慢性HBV感染者,每年约有100万人死于HBV感染所致的肝衰竭、肝硬化和原发性肝细胞癌(HCC).治疗慢性乙型肝炎的总体目标是最大限度地长期抑制HBV复制,减轻肝细胞炎症坏死及肝纤维化,延缓和减少肝脏失代偿、肝硬化、肝细胞癌及其并发症的发生,从而改善生活质量和延长存活时间[1].恩替卡韦(ETV,博路定)为环戊酰鸟苷类似物,被广泛用于治疗慢性乙型肝炎(CHB),对于初次抗病毒治疗患者和拉米夫定治疗失效患者均具有显著的抗HBV作用[2].     

恩替卡韦、拉米夫定治疗HBeAg阳性慢性乙型肝炎的疗效观察

我们于2007年5B开始,对不同基线ALT水平的HBeAg阳性慢性乙型肝炎患者200例,分别应用恩替卡韦(ETV)和拉米夫定(LVD)治疗,观察其疗效,现报道如下.     

恩替卡韦治疗HBeAg阳性慢性乙型肝炎早期ALT升高的临床特征

目的探讨恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者,观察早期ALT的变化。方法 60例HBeAg阳性慢性乙型肝炎患者口服恩替卡韦治疗。结果在60例患者中,30例患者在治疗后平均3周ALT达到峰值,他们治疗前HBV DNA平均载量为8.64±0.99lg拷贝/毫升,而另30例ALT未上升患者为7.09±1.33lg拷贝/毫升(P0.05);口服恩替卡韦治疗12周,ALT上升与未上升患者HBV DNA转阴率分别为73.3%和80.0%,ALT复常率分别为53.3%和76.7%(P0.05)。结论口服恩替卡韦治疗HBeAg阳性慢性乙型肝炎,50%患者会出现早期ALT上升,其意义需要观察。     

替比夫定与恩替卡韦治疗HBeAg阳性慢性乙型肝炎4年随访观察

目的比较替比夫定(LdT)和恩替卡韦(ETV)治疗HBeAg阳性的CHB,哪一个能较早地实现有限疗程。方法 60例HBeAg阳性的CHB患者随机分为LdT组和ETV组。在服药后第12周、24周及以后每24周复查,直至治疗和随访结束(4年,192周),检测血清HBV DNA定量、HBV血清标志物、肝功能、血清肌酸激酶。观察两组192周治疗结束时应答率及持续应答率以及患者达到停药标准所需的时间及费用。结果 192周时LdT组和ETV组治疗结束时应答率及持续应答率为43.3%(13/30)vs 16.7%(5/30)、36.7%(11/30)vs 10.0%(3/30),差异有统计学意义(P<0.05)。达到停药标准LdT组平均治疗时间为167.2周,费用28 089.6元,而ETV组平均治疗时间为186.4周,费用50 887.2元。结论治疗HBeAg阳性的CHB患者,实现有限疗程LdT更具有优势。     

替比夫定和恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者早期疗效分析

目的比较替比夫定与恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者24周疗效及安全性。方法将60例HBeAg阳性慢性乙型肝炎患者随机分为替比夫定组和恩替卡韦组,比较两组治疗第12周和24周的疗效。结果在治疗12周时,两组患者HBV DNA低于检测水平和ALT复常率相比较,差异无统计学意义（P〉0.05）,替比夫定治疗组HBeAg阴转率和HBeAg血清学转换率高于恩替卡韦组（36.7%对14.3%,26.7%对6.7%,P〈0.05）;在治疗24周时,两组HBV DNA低于检测水平、ALT复常率、HBeAg血清学转换率相比较,差异均无统计学意义（P〉0.05）,而替比夫定组HBeAg阴转率高于恩替卡韦组（P〈0.05）;多因素Logistic回归分析发现仅基线ALT水平高的患者更易出现HBeAg血清学转换。结论替比夫定和恩替卡韦治疗CHB患者疗效相当,但替比夫定治疗患者HBeAg阴转率稍高于恩替卡韦治疗。     

血清HBsAg浓度对慢性乙型肝炎患者抗病毒药物治疗效果的预测作用

目的:动态监测慢性乙型肝炎患者接受恩替卡韦(entecavir,ETV)治疗过程中的乙型肝炎表面抗原(hepatitis B surface antigen,HBsAg)水平,探讨HBsAg水平对治疗效果的预测价值.方法:严格入选90例慢性乙型肝炎患者,进行1年的E T V治疗,于0、3、6、9、12 m o检测HBs Ag、乙型肝炎病毒(hepatitis B virus,HBV)DNA水平,采用t检验、Pearson相关性分析、受试者工作特征(receiver operating characteristic,ROC)曲线等进行分析.结果:52例(57.78%)患者经治疗后有效,38例(42.22%)无效,有效组年龄明显高于无效组,HBs Ag、HBV DNA水平明显低于无效组(P0.05);有效组和无效组HBs Ag及HBV D N A水平均呈下降趋势,有效组下降速度明显快于无效组(P0.05);HBs Ag和HBV DNA呈明显的正相关关系(r=0.5353,P0.0001);各时点HBs Ag水平对ETV抗病毒治疗有效具有预测价值,ROC曲线下的面积从小到大依次为:治疗3 mo基线治疗6 mo治疗9 mo治疗12 mo.结论:慢性乙型肝炎患者血清HBs Ag水平,可以作为其抗病毒有效性的预测因子,其检测简单、经济、可靠,值得在临床上推广使用.     

HBsAg levels in HBeAg-positive chronic hepatitis B patients with different immune conditions

AIM:To investigate hepatitis B surface antigen(HBsAg)levels in patients with HBeAg-positive chronic hepatitis B(CHB)and different immune conditions.METHODS:HBeAg-positive CHB patients with different immune conditions were enrolled in this cross-sectional study.These patients were grouped according to the following criteria:immune-tolerant patients,IT group;patients with a mild immune response in the immune clearance phase,IC-Mild group;and patients with a dramatic immune response in the immune clearance phase and exhibiting acute on chronic liver failure(ACLF),ACLF group.All these patients had not previously received antiviral therapy and were enrolled at a pre-settled ratio of2:2:1.Serum HBsAg levels and the correlation between serum HBsAg level and serum hepatitis B virus(HBV)DNA level were evaluated in these groups.RESULTS:In total,180 HBeAg-positive CHB patients[IT group(n=72),IC-Mild group(n=72),and ACLF group(n=36)]were enrolled in this study.The median serum HBsAg levels varied among the groups(P<0.001):IT,4.86 log10IU/mL;IC-Mild,3.97 log10IU/mL;and ACLF,3.57 log10IU/mL.Serum HBsAg level showed a moderate positive correlation with serum HBV-DNA level in the IC-Mild group(r=0.60,P<0.001),but exhibited a weaker correlation in the IT(r=0.52,P<0.001)and ACLF groups(r=0.51,P=0.001).The ratio of HBsAg/HBV DNA did not differ significantly among the IT,IC-Mild,and ACLF groups(medians:0.56,0.55,and 0.56,respectively;P=0.179).CONCLUSION:Serum HBsAg levels varied significantly in HBeAg-positive patients with different immune conditions.These findings may have important implications for understanding the immune clearance of HBV in HBeAg-positive CHB patients.     

Prediction of response to entecavir therapy in patients with HBeAg-positive chronic hepatitis B based on on-treatment HBsAg, HBeAg and HBV DNA levels

Summary. Quantitative hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) assays are emerging as effective tools of on‐treatment predictors of response to antiviral agents, in addition to monitoring serum HBV DNA levels. However, the dynamic relationship between quantitative HBsAg, as well as HBeAg and HBV DNA, and the predictability of subsequent clinical outcomes during entecavir (ETV) therapy remain unclear. Eighty‐two patients with HBeAg‐positive chronic hepatitis B (CHB) received ETV therapy for ≥3 years. Virologic response (VR) after 3 years of ETV therapy was achieved in 73 (89.0%) patients. Among baseline and on‐treatment factors, on‐treatment HBV DNA levels performed better with respect to the prediction of response than HBsAg and HBeAg levels. Especially, the performance of absolute values of HBV DNA with respect to response was superior to HBV DNA decline from the baseline. The best predictive value was an absolute HBV DNA level of 2.3 log₁₀ IU/mL at month 6 (areas under the curve [AUROC], 0.977; 95% CI, 0.940–1.000; P < 0.001). HBeAg seroconversion after 3 years of therapy was achieved in 26 (31.7%) patients. On‐treatment HBeAg levels performed better with respect to the prediction of seroconversion than HBsAg and HBV DNA levels. The best cut‐off value for the HBeAg level at month 12 for the prediction of seroconversion was 0.62 log₁₀ PEIU/mL. Although the HBsAg level at baseline is often used to predict the antiviral potency of entecavir, on‐treatment HBV DNA and HBeAg levels are more helpful for prediction of subsequent clinical outcomes in HBeAg‐positive CHB patients with entecavir treatment.     

恩替卡韦治疗藏族 HBeAg 阳性的慢性乙型肝炎患者临床疗效分析

目的：评价恩替卡韦治疗藏族 HBeAg 阳性的慢性乙型肝炎患者的临床疗效。方法60例 HBeAg 阳性的藏族慢性乙型肝炎患者接受口服恩替卡韦0.5 mg/d 治疗48 w。每3个月随访1次,治疗12周及48周时复查肝功能及 HBV DNA,并记录不良反应事件。结果在观察期结束时,有80%患者达到 HBV DNA 阴转,有75.4%患者达到 ALT 复常,有7%患者达到 HBeAg血清学转阴,有3%患者达到 HBeAg 血清学转换。在治疗过程中没有患者出现 HBsAg 转阴。结论恩替卡韦治疗藏族 HBeAg 阳性慢乙型肝炎患者具有持续抑制病毒复制的作用,安全性较好。     

恩替卡韦治疗e抗原阴性慢性乙型肝炎停药后复发的分析

目的了解HBeAg阴性的慢性乙型肝炎(CHB)患者使用恩替卡韦抗病毒治疗的疗程及停药的标准。方法回顾性分析2006年1月至2015年12月复旦大学附属中山医院肝炎门诊确诊为HBeAg阴性的CHB并予恩替卡韦抗病毒治疗后停药6月以上的患者121例,观察其停药6个月、12个月的HBV DNA水平、肝功能。结果停药6个月后有33%的患者HBV DNA5×10~2拷贝/mL,19.8%患者出现ALT升高。停药12个月后累计有45.5%的患者HBV DNA5×10~2拷贝/mL,30.6%患者出现ALT升高,用药大于5年的患者复发率最低。此外,基线HBV DNA水平2×10~5拷贝/mL的患者停药后6个月、12个月的复发率较基线水平10~7拷贝/mL者低。结论 HBeAg阴性的CHB患者使用恩替卡韦治疗停药复发的比率随着抗病毒疗程的延长而减少,且基线HBV DNA水平与复发率相关。     

A one-year trial of entecavir treatment in patients with HBeAg-positive chronic hepatitis B

To evaluate the efficacy and safety of entecavir （ETV） in hepatitis Be antigen （HBeAg）-positive chronic hepatitis B （CriB） patients who had not received a nucleoside analogue and who had failed in lamivudine （LVD） therapy. METHODS： Sixty-one patients were divided into three groups. Forty-two patients who had not received a nucleoside analogue were randomized into two groups： group A （n = 21） received LVD 100 mg/d and group B （n -- 21） received ETV 0.5 mg/d. The remaing 19 patients treated with LVD （n = 19）, who switched to ETV 1.0 mg/d served as group C. All patients were treated for 48 wk. HBV DNA levels were measured with polimerase- chain-reaction （PCR） analysis. Liver function tests, HBV serology and safety assessments were also conducted. RESULTS： Significantly more patients in group B （52.1% and 71.4%） had undetectable HBV DNA levels than in groups A （35.8% and 38%; P 〈 0.0001） and C （10.6% and 21.1%, P 〈 0.0001） at wk 24 and 48, respectively. At wk 48, ALT levels were normalized in more patients in group B （85.7%） than in groups A （76.2%） and C （74%）. CONCLUSION： ETV had a significantly higher response rate than LVD in patients with HBeAg-positive CriB who had not previously received a nucleoside analogue; ETV can effectively inhibit the replication of HBV DNA and normalize the levels of ALT in refractory CriB patients treated with LVD; and ETV is safe in clinical application.     

恩替卡韦联合干扰素治疗e抗原阳性慢性乙型肝炎疗效观察

目的 观察恩替卡韦抗病毒治疗有效患者联合干扰素抗病毒治疗后HBsAg及HBeAg的变化.方法 将40例患者分为试验组和对照组,试验组在恩替卡韦治疗的基础上加用干扰素抗病毒治疗,对照组继续恩替卡韦抗病毒治疗,分别在12周和24周定量检测两组患者HBsAg及HbeAg的变化.结果 治疗12周时,两组患者HBsAg和HBeAg均有一定程度的下降,但与治疗前比较差异无统计学意义(P＞0.05);治疗24周时,试验组患者HBsAg和HBeAg与治疗前比较均明显下降(P＜0.05),与对照组比较差异有统计学意义(P＜0.05).结论 恩替卡韦抗病毒治疗有效的患者加用干扰素继续抗病毒治疗,提高HBeAg血清转换率,有可能缩短疗程.     

Pretreatment HBeAg level and an early decrease in HBeAg level predict virologic response to entecavir treatment for HBeAg-positive chronic hepatitis B

There are few reports on hepatitis B e antigen (HBeAg) titres during nucleos(t)ide analogues treatment. We investigated the changes in HBeAg levels in patients treated with entecavir and the usefulness of HBeAg quantification for predicting antiviral response. Ninety-five consecutive HBeAg-positive patients treated with entecavir for more than 48 weeks were enrolled. Serum levels of hepatitis B surface antigen (HBsAg), HBeAg and HBV DNA were assessed at 4-week intervals to week 24 and thereafter at 12-week intervals. Virologic response (Y1VR) was defined as an undetectable HBV DNA level at week 48 of therapy. During 48 weeks, HBeAg and HBV DNA level decreased significantly in a biphasic manner and HBsAg level tended to decease. Fifty-three patients (55.8%) attained Y1VR. Pretreatment HBeAg levels were significantly lower in the Y1VR group than in no Y1VR group. At week 4 and 12 of therapy, 25% and 41.4% of patients showed a decrease of HBeAg levels with >0.5 log(10) and >1.0 log(10) from baseline, respectively. These patients achieved more Y1VR than those with less decrease of HBeAg levels (97.7%vs 22.2% and 86.2%vs 29.3%, respectively). HBeAg level at week 12 had higher predictive values for Y1VR than HBV DNA level. Multivariate analysis revealed that a pretreatment HBeAg level of <360 PEIU/mL and the reduction in HBeAg level >1.0 log(10) at week 12 were associated with Y1VR. These results suggest that pretreatment HBeAg level and an early decrease in HBeAg level are useful measurements for predicting one-year virologic response during entecavir treatment.     

Models for predicting hepatitis B e antigen seroconversion in response to interferon-α in chronic hepatitis B patients

AIM:To develop models to predict hepatitis B e antigen(HBe Ag)seroconversion in response to interferon(IFN)-αtreatment in chronic hepatitis B patients.METHODS:We enrolled 147 treatment-nave HBe Agpositive chronic hepatitis B patients in China and analyzed variables after initiating IFN-α1b treatment.Patients were tested for serum alanine aminotransferase(ALT),hepatitis B virus-DNA,hepatitis B surface antigen(HBs Ag),antibody to hepatitis B surface antigen,HBe Ag,antibody to hepatitis B e antigen(anti-HBe),and antibody to hepatitis B core antigen(anti-HBc)at baseline and 12 wk,24 wk,and 52 wk after initiating treatment.We performed univariate analysis to identify response predictors among the variables.Multivariate models to predict treatment response were constructed at baseline,12 wk,and 24 wk.RESULTS:At baseline,the 3 factors correlating most with HBe Ag seroconversion were serum ALT level4×the upper limit of normal(ULN),HBe Ag≤500 S/CO,and anti-HBc11.4 S/CO.At 12 wk,the 3 factors most associated with HBe Ag seroconversion were HBe Ag level≤250 S/CO,decline in HBe Ag1 log10 S/CO,and anti-HBc11.8 S/CO.At 24 wk,the 3 factors most associated with HBe Ag seroconversion were HBe Ag level≤5 S/CO,anti-HBc11.4 S/CO,and decline in HBe Ag2 log10 S/CO.Each variable was assigned a score of1,a score of 0 was given if patients did not have any of the 3 variables.The 3 factors most strongly correlating with HBe Ag seroconversion at each time point were used to build models to predict the outcome after IFN-αtreatment.When the score was 3,the response rates at the 3 time points were 57.7%,83.3%,and 84.0%,respectively.When the score was 0,the response rates were 2.9%,0.0%,and 2.1%,respectively.CONCLUSION:Models with good negative and positive predictive values were developed to calculate the probability of response to IFN-αtherapy.