恩替卡韦治疗慢性乙型肝炎肝衰竭临床研究

目的观察恩替卡韦治疗慢性乙型肝炎肝衰竭的疗效。方法对20例慢性乙型肝炎肝衰竭患者在综合治疗的基础上加用恩替卡韦治疗,16例患者为对照组,观察3个月的疗效。结果治疗组存活14例（70.0%）,对照组存活9例（56.3%,P〉0.05）,但治疗组患者血清HBV DNA全转阴。结论恩替卡韦治疗慢性乙型肝炎肝衰竭可强效抑制病毒复制,能否提高存活率还有待观察。     

恩替卡韦治疗慢性乙型肝炎患者疗效观察

目的观察恩替卡韦治疗CHB患者的疗效。方法 43例HBeAg阳性和18例HBeAg阴性患者接受恩替卡韦治疗,比较两组治疗24周和48周时的疗效。结果在治疗24周时,HBeAg阳性组HBV DNA转阴15例（34.9%）4,8周时转阴28例（65.1%）,而HBeAg阴性组分别转阴15例（83.3%）和17例（94.4%,P=0.001和0.018）;两组在24周和48周时ALT复常率均无显著性差异（P=0.713和0.138）;在34例HBV DNA定量〉10^7copies/ml与27例HBV DNA定量〈107copies/ml两组中,治疗24周时,HBV DNA转阴例数分别为11例（32%）和19例（70%,P=0.03）,治疗48周时,则分别为23例（68%）和22例（81%,P=0.22）。结论本研究提示恩替卡韦治疗CHB有很好的抗病毒活性。     

恩替卡韦治疗慢性乙型肝炎的临床研究

目的评价恩替卡韦治疗慢性乙型肝炎(CHB)的疗效和安全性。方法72例CHB患者随机分配到治疗组和对照组,治疗组(30例)予恩替卡韦0.5mg/d;对照组(42例)予拉米夫定100mg/d疗程均48周,基础治疗相似。结果治疗组和对照组在治疗24周、48周时:血清HBV-DNA水平比基线值(log10copies/ml)平均下降分别为5.48、6.87和2.84、5.38;病毒应答率分别为53%、67%和21%、43%。均P<0.001,两组均有显著差异。ALT复常率分别为67%、77%和60%、67%,血清HBeAg阴转率、HBsAg消失率、不良事件发生率,均P>0.05,差异无统计学意义。无严重不良反应发生。结论恩替卡韦治疗慢性乙型肝炎,可在病毒学及生物化学方面取得显著疗效,且安全性良好,无耐药发生。     

恩替卡韦替代拉米夫定治疗慢性乙型肝炎的疗效观察

目的观察恩替卡韦(ETV)替代拉米夫定(LAM)治疗未出现病毒变异的拉米夫定经治慢性乙型肝炎患者的疗效。方法 43例经拉米夫定治疗96周而没有出现病毒学突破的慢性乙型肝炎患者,分为2组,A组23例继续服用拉米夫定,100mg/d;B组20例,改口服恩替卡韦,0.5mg/d,随访3年,每12周检测患者肝功能、HBVDNA定量。结果 A组在继续治疗的第48、96、144周出现病毒学突破的患者数分别为2、6、9例。B组在换药的第48、96、144周出现病毒学突破的患者数分别为0、0、1例。结论恩替卡韦替代拉米夫定治疗未出现耐药的拉米夫定经治慢性乙型肝炎患者,其疗效与恩替卡韦初治相仿。     

慢性乙型肝炎恩替卡韦治疗后的血清病毒学变化特征

目的研究恩替卡韦（ETV）治疗初治和拉米夫定（LAM）耐药慢性乙型肝炎（CHB）患者的病毒学应答和耐药。方法50例CHB患者按ETV治疗时机分2组：A组为ETV初治患者25例,患者口服ETV0.5mg/次,每日1次;B组为LAM耐药患者25例,患者口服ETV1.0mg/次,每日1次。疗程中监测患者肝功能和HBV DNA载量,在48周后HBV DNA仍大于4log10拷贝/ml或病毒学突破时,提取患者血清HBV DNA直接测序进行耐药变异分析。结果A组基线、12周、24周、48周、96周HBV DNA载量分别为（7.85±0.83）log10拷贝/ml、（3.24±0.97）log10拷贝/ml、（2.96±0.59）log10拷贝/ml、（2.86±0.52）log10拷贝/ml、（2.70±0）log10拷贝/ml;而B组基线、12周、24周、48周、96周HBV DNA载量分别为（6.41±1.43）log10拷贝/ml、（3.76±0.89）log10拷贝/ml、（2.72±0.09）log10拷贝/ml、（3.14±1.22）log10拷贝/ml、（3.04±1.06）log10拷贝/ml。A组DNA转阴率12周、24周、48周、96周分别为64.0%、80.0%、84.2%、94.4%,B组DNA转阴率12周、24周、48周、96周时分别为32.0%、68.0%、80.0%、88.2%。A组未发现ETV耐药变异,B组患者共有3例（12.0%）发生耐药,48周和96周ETV基因型耐药率分别为4.0%、12.0%。结论ETV治疗初治和LAM耐药患者均有较好病毒学应答,但LAM耐药患者较初治患者ETV累积耐药率高。     

恩替卡韦治疗拉米夫定失效的慢性乙型肝炎7例临床观察

我们采用恩替卡韦(1.0mg/d)治疗7例拉米夫定治疗失效的患者,取得一定疗效,现报道如下。资料与方法7例均为我院门诊患者,诊断符合2000年9月中华医学会传染病与寄生虫病学分会、肝病学分会联合修订的《病毒性肝炎的诊断标准》。年龄(32±7)岁,HBeAg均阳性,服用拉米夫定至少1年,服     

恩替卡韦治疗慢性乙型肝炎临床观察

目的评价恩替卡韦分散片治疗慢性乙型肝炎的抗病毒疗效及安全性。方法 30例慢性乙型肝炎患者口服恩替卡韦分散片,另30例对照组口服恩替卡韦,治疗48周。结果治疗组和对照组在治疗48周时,HBV DNA阴转率、HBeAg转阴率和ALT复常率分别为83.3%对86.6%、43.3%对46.6%和100%对100%（P〉0.05）。结论恩替卡韦分散片在治疗慢性乙型肝炎方面具有显著的抗病毒作用,疗效与恩替卡韦片相当,是一种安全有效的治疗药物。     

恩替卡韦治疗维持性血液透析慢性乙型肝炎的疗效

目的探讨维持性血液透析的慢性乙型肝炎病人应用恩替卡韦抗病毒治疗的疗效及安全性。方法 56例维持性血液透析的慢性乙型肝炎病人均相应的给予保肝、降酶等常规治疗;治疗组加用恩替卡韦5 mg,每隔5 d服药1次,总疗程为48 w。比较两组患者治疗12、24、48 w时的谷丙转氨酶(ALT)、肌酐(CRE)和乙肝病毒(HBV)-DNA定量。结果治疗组12 w 8例HBV-DNA<500 cps/ml,24 w时24例全部HBV-DNA<500 cps/ml;对照组12、24、48 w 32例HBV-DNA水平分别为(6.03±1.17)、(5.78±1.01)、(5.67±0.97)log10 cps/ml,HBV-DNA水平有所下降,但无统计学意义,且无1例HBV-DNA<500 cps/ml。治疗组12 w ALT(100.7±54.0)U/L与对照组ALT(108.3±59.0)U/L比较无统计学差异(P>0.05);治疗组24 w ALT(58.6±26.9)U/L与对照组(80.8±32.6)U/L比较差异显著(P<0.01);治疗组48 w ALT(41.5±14.6)U/L与对照组(51.6±19.3)U/L比较有统计学差异(P<0.05)。治疗组12、24、48 w CRE(873.8±265.8)μmol/L、(842.8±268.3)μmol/L、(768.9±213.6)μmol/L与对照组(791.0±248.1)μmol/L、(803.8±206.6)μmol/L、(845.8±230.4)μmol/L比较无统计学差异(P>0.05)。结论在维持性血液透析的慢性乙型肝炎的病人中,应用恩替卡韦抗病毒治疗安全、有效,利于肝功能恢复。     

恩替卡韦治疗慢性乙型肝炎33例疗效观察

目的观察恩替卡韦治疗慢性乙型肝炎疗效。方法随机选取慢性乙型肝炎患者33例,在给予一般保肝药物治疗同时,再给予口服恩替卡韦治疗,疗程48周,跟踪12周。对照组31例仅给予一般保肝药物治疗。结果恩替卡韦组治疗48周时78.8%腹胀乏力、纳差等临床症状明显改善,跟踪12周,只有11.5%出现反复,而对照组有73.9%出现病情波动,差异有统计学意义（P〈0.01）。恩替卡韦组治疗48周时84.4%ALT复常,仅10.7%出现ALT再次升高,与对照组76.9%相比差异有统计学意义（P〈0.01）。另外,疗程48周时,恩替卡韦组HBeAg转阴率42.4%、HBV-DNA转阴率78.8%均明显高于对照组（3.2%、9.7%）,差异有统计学意义（P〈0.01）。结论恩替卡韦治疗乙型肝炎具有较好的疗效,且无明显不良反应,能延缓和阻止疾病进展。     

慢性乙型肝炎不规范停用恩替卡韦复发后再次恩替卡韦治疗的临床效果

目的观察慢性乙型肝炎患者对恩替卡韦停药后再次使用恩替卡韦复治的疗效。方法选取了自2013年2月至2017年2月间在我院治疗的慢性乙肝患者79例,分为复发组和初治组,复发组患者共42例,均为使用恩替卡韦治疗1年以上,HBV DNA已转阴,因自行停药后,HBV DNA再次转阳的患者。初治组患者共37例,为首次接受恩替卡韦治疗的患者。两组均予以恩替卡韦分散片0.5 mg/d口服抗病毒治疗,比较两组患者在治疗的第4周、第8周和第16周时肝功能、乙肝五项和HBV DNA病毒载量的情况。结果经过恩替卡韦治疗4周,复发组(11.9%)与初治组(43.2%)患者肝功能指标恢复正常,两组比较(P0.01);复发组(59.5%)与初治组(35.1%)患者HBV DNA转阴,两组比较(P0.05)。经过恩替卡韦治疗8周,复发组(40.5%)与初治组(78.45%)患者肝功能指标恢复正常,两组比较(P0.01);复发组(92.9%)与初治组(75.7%)患者HBV DNA转阴,两组比较(P0.05)。经过恩替卡韦治疗16周,复发组(69.0%)与初治组(89.2%)患者肝功能指标恢复正常,两组比较(P0.05);复发组(92.9%)与初治组(75.7%)患者HBV DNA转阴,两组比较(P0.05);复发组(73.8%)与初治组(51.4%)患者HBeAg血清学转换率,两组比较(P0.05),两组治疗后HBsAg滴度下降50%的患者比率没有显著统计学差异(P0.05)。结论对恩替卡韦不规范停药后复发的慢性乙型病毒性肝炎患者再次服用恩替卡韦仍然有效且安全,值得在临床上进一步推广。     

Long-term efficacy of entecavir therapy in chronic hepatitis B patients with antiviral resistance to lamivudine and adefovir

No studies have reported the long-term effects of entecavir switching in patients with multidrug resistance who developed resistance after lamivudine/adefovir sequential therapy. We evaluated the efficacy of 96 weeks of entecavir therapy in patients with resistance to lamivudine/adefovir sequential therapy. In total, 33 patients with chronic hepatitis B virus (HBV) infection with evidence of active viral replication (HBV DNA levels ≥ 10(5) copies/mL) or a history of treatment failure to lamivudine/adefovir sequential therapy between April 2007 and July 2009 were treated with entecavir (1.0 mg daily) for at least 48 weeks. The rates of alanine transaminase (ALT) normalization and HBV DNA negativity were 66.7% (14/21) and 24.2% (8/33) at 48 weeks, respectively. The initial HBV DNA level was the only factor that was inversely associated with serum HBV DNA negativity after 48 weeks of entecavir therapy (P < 0.023). At 96 weeks, the rates of ALT normalization and HBV DNA negativity were 77.8% (7/9) and 16.7% (3/18), respectively. Viral breakthrough occurred in 21.2% (7/33) and 78.9% (15/19) of patients at 48 and 96 weeks, respectively. Patients who achieved a HBV DNA level of <4 log(10) copies/mL at 48 weeks maintained a similar HBV DNA level and a normal ALT level until 96 weeks. Entecavir monotherapy for 96 weeks was not efficacious for patients with lamivudine/adefovir-resistant HBV. The initial HBV DNA level was the only predictive factor for antiviral efficacy. However, patients who achieved a HBV DNA level of <4 log(10) copies/mL with a normal ALT level at 48 weeks should maintain, rather than stop, entecavir therapy.     

Economic analysis between entecavir and lamivudine for the treatment of chronic hepatitis B in Hong Kong

Background and Aim: Tremendous healthcare resources have been spent on the management of chronic hepatitis B (CHB) and its related complications. Therefore, a proper evaluation of the cost‐effectiveness of pharmacotherapy is vital in aid of decision‐making. The aim of the present study was to examine the long‐term economic and clinical influence if lamivudine was replaced by entecavir in a group of CHB patients. Methods: A recently published decision analytic model was adapted to study the cost‐effectiveness of 2 years of treatment of entecavir in a hypothetical cohort of 1000 hepatitis B e antigen (HBeAg)‐negative CHB patients from a public hospital perspective. Compensated cirrhosis (CC) and de‐compensated cirrhosis (DC) and hepatocellular carcinoma (HCC) events were projected to 10 years. Hong Kong‐specific health care costs were used. Quality Adjusted Life Years (QALYs) were calculated using the utility values obtained from a local study. Results: In the base case analysis, compared with lamivudine, the use of entecavir was expected to reduce the incidences of CC, DC and HCC by 41.8%, 57.1% and 49.3%, respectively, and lead to a saving of $US 1.17 million in medical cost. The overall disease management cost for entecavir, which was 67.7% higher than lamivudine for 2 years treatment was reduced to 17.2% after projecting 2‐year treatment duration to 10 years. The incremental cost per QALY gained for entecavir compared with lamivudine was $US 13 759. Conclusions: Based on the recommended cost‐effectiveness threshold of the World Health Organization, entecavir is considered cost‐effective compared with lamivudine in treating CHB in Hong Kong when long term medical consequences were considered.     

恩替卡韦治疗慢性乙型肝炎的疗效观察

目的评价恩替卡韦治疗慢性乙型肝炎(CHB)患者96周的疗效。方法收集2011年7月-2014年7月在江苏省泰兴市人民医院门诊和住院的62例CHB患者,给予恩替卡韦0.5 mg/d抗病毒治疗96周。所有病例分为两组,HBe Ag阳性组患者43例,HBe Ag阴性组患者19例。其中HBV DNA106拷贝/ml患者38例,HBV DNA106拷贝/ml患者24例。比较两组治疗24、48及96周的疗效。计数资料组间比较采用χ2检验。结果在治疗24、48、96周时,HBe Ag阳性组患者HBV DNA阴转率分别为34.88%、65.12%、74.42%,明显低于HBe Ag阴性组的78.95%、89.47%、100%,差异均有统计学意义(P值分别为0.003、0.047、0.038)。两组患者的ALT复常率差异均无统计学意义(P值分别为0.102、0.779、0.638)。在38例HBV DNA载量106拷贝/ml和24例HBV DNA载量106拷贝/ml的两组中,治疗24、48、96周时,两组患者HBV DNA阴转率差异均有统计学意义(34.21%vs70.83%、57.89%vs 95.83%、76.32%vs 95.83%,P值分别为0.005、0.001、0.002);两组患者ALT复常率差异均无统计学意义(P值分别为0.940、0.150、0.280)。结论恩替卡韦治疗CHB有很好的抗病毒活性,在抑制病毒复制的同时能改善肝功能。     

恩替卡韦治疗慢性乙型肝炎肝硬化失代偿期患者的近期疗效及安全性

目的：观察恩替卡韦治疗慢性乙型肝炎（CriB）肝硬化失代偿期患者的近期疗效及安全性。方法：选取44例CHB肝硬化失代偿期患者,随机分为恩替卡韦组（22例）和拉米夫定组（22例）。两组患者均给予综合治疗,其中恩替卡韦组患者加用恩替卡韦0．5mg／次口服,1次／d;拉米夫定组患者加用拉米夫定100mg／次口服,1次/d。每周检测两组患者HBVDNA、ALT、Alb、TBil、PTA（凝血酶源活动度）及乳酸（Lactate）等指标变化,连续8周。结果：两组患者HBVDNA水平均从治疗第2周开始逐渐下降,但恩替卡韦组患者HBVDNA水平在治疗后第5周下降到低于检测下限（〈5×10^2拷贝／m1）,明显快于拉米夫定组。从治疗第5周开始,恩替卡韦组患者Alb、TBil及PTA指标较拉米夫定组患者有更明显的改善。在8周的观察期内,有9例患者死亡（MELD评分均〉25）,其中恩替卡韦组4例,拉米夫定组5例,两组之间病死率比较差异无显著性意义（P〉0．05）。9例死亡患者均有不同程度的高乳酸血症（2．0～4．0mmol／L）,但无乳酸酸中毒发生。结论：恩替卡韦较拉米夫定有更显著的抗病毒活性,可在短期内较迅速改善CHB肝硬化失代偿期患者病情。恩替卡韦或拉米夫定均无明显的药物不良反应。血清乳酸水平的升高主要与患者病情严重有关。     

Efficacy and safety of entecavir in lamivudine-refractory patients with chronic hepatitis B: randomized controlled trial in Japanese patients

Background and Aim:  Entecavir is a potent inhibitor of both wild-type and lamivudine-resistant hepatitis B virus (HBV) with proven clinical efficacy. We conducted a randomized, double-blind, multicenter study in Japan (ETV-052) evaluating the efficacy and safety of two doses of entecavir in adult patients with lamivudine-refractory chronic hepatitis B infection.
Methods:  Eighty-four patients with chronic hepatitis B who were refractory to lamivudine therapy were switched from lamivudine to daily oral doses of 0.5 mg entecavir (41 patients) or 1 mg entecavir (43 patients) for 52 weeks.
Results:  The proportions of patients achieving the primary end-point (≥2 log₁₀ reduction in HBV-DNA from baseline by polymerase chain reaction assay or undetectable HBV-DNA levels [<400 copies/mL] at week 48) were 90% and 93% for entecavir 0.5 mg and 1 mg, respectively, with 33% of patients in each dosing group achieving <400 copies/mL. The mean reduction in HBV-DNA from baseline was 3.58 and 3.75 log₁₀ copies/mL for entecavir 0.5 mg and 1 mg, respectively. High proportions of patients achieved alanine aminotransferase normalization at week 48 (0.5 mg 86%, 1 mg 78%). Histological improvement was observed in most patients (0.5 mg 52%, 1 mg 60%). Virological breakthrough (increase in HBV-DNA of ≥1 log₁₀ copies/mL from nadir) was observed in one patient but was not associated with selection of entecavir-associated resistance substitutions. Entecavir was well tolerated, with no patients discontinuing study drug due to adverse events.
Conclusions:  These findings indicate that entecavir is safe and effective for the treatment of Japanese adults with lamivudine-refractory chronic hepatitis B.     

Short-term entecavir therapy of chronic severe hepatitis B

BACKGROUND:Chronic severe hepatitis B patients often have limited survival.This investigation aimed to evaluate the short-term effects of nucleoside analog therapy on chronic severe hepatitis B. METHODS:We retrospectively,randomly collected the data of 129 chronic severe hepatitis B patients:55 were treated with entecavir,and the remaining 74 were not treated with nucleoside analogues. RESULTS:No significant difference in short-term survival rate was found between the group treated with entecavir and that t...     

抗病毒基础上应用糖皮质激素治疗慢性重型乙型肝炎临床分析

目的 评价在抗病毒治疗的基础上应用糖皮质激素治疗早期慢性重型乙型肝炎的临床疗效.方法 选取63例早期慢性重型乙型肝炎患者,随机分为治疗组33例,对照组30例,其中治疗组在综合治疗的基础上应用拉米夫定或恩替卡韦抗病毒及地塞米松等糖皮质激素治疗.对照组30例采用拉米夫定或恩替卡韦抗病毒及常规综合治疗.观察两组治疗前后的临床症状、血清总胆红素、凝血酶原活动度、HBVDNA及并发症等情况.结果 8周后与对照组比较,治疗组患者血清总胆红素明显降低(P＜0.05),凝血酶原活动度提升幅度大(P＜0.05),肝性脑病、肝肾综合征等并发症减少(P＜0.05),临床症状明显好转.4周后血清PCRHBVDNA阴转率为87.1%与对照组的85.1%相比,差异无统计学意义(P＞0.05),治疗组的治疗失败率为15.2%(5/33)明显低于对照组的40.0%(12/30)(P＜0.05).结论 在抗病毒治疗的基础上应用糖皮质激素对早期慢性重型乙型肝炎疗效显著,安全性好.     

Long-term efficacy of entecavir in adefovir-refractory chronic hepatitis B patients with prior lamivudine resistance

This study aimed to evaluate the long-term efficacy of entecavir (ETV) in adefovir (ADV)-refractory chronic hepatitis B (CHB) patients with prior lamivudine (LMV) resistance. A total of 55 ADV-refractory CHB patients with prior LMV resistance, who received rescue therapy with ETV 1 mg daily for at least 12 months, were consecutively enrolled and analysed. Forty-four patients were men, and their median age was 47 (25-69). Ten patients had liver cirrhosis and 46 patients were positive for hepatitis B e antigen (HBeAg). Median hepatitis B virus DNA levels were 6.6 (4.3-8.0) log(10) copies/mL, and the median duration of ETV therapy was 24 (12-47) months. Cumulative virologic response rates at 6, 12, 24 and 36 months were 18%, 29%, 58% and 75%, respectively. HBeAg loss occurred in 10 (21.7%) of 46 HBeAg-positive patients. In multivariate analysis, only initial virologic response at 3 months remained as an independent predictor for virologic response (RR 3.143; 95% CI 1.387-7.120; P = 0.006). The patients with a virological response at 3 months had not only a significantly higher probability of achieving a virologic response (P < 0.001) but also lower probability of experiencing a virologic breakthrough (P = 0.043) than the patients without an early response. Viral breakthrough was observed in 29 patients during the follow-up period. Cumulative breakthrough rates at 6, 12, 24 and 36 months were 0%, 15%, 45% and 73%, respectively. ETV monotherapy may be considerably efficacious in cases with an initial virological response but its efficacy is attenuated by frequent emergence of ETV resistance in ADV-refractory CHB patients with prior LMV resistance.     

Efficacy of entecavir treatment for lamivudine‐resistant hepatitis B over 3 years: Histological improvement or entecavir resistance?

Background and Aims:  Long-term lamivudine therapy is required for patients with chronic hepatitis B, because hepatitis reappears frequently after it has withdrawn. However, hepatitis B virus (HBV) mutants resistant to lamivudine emerge frequently accompanied by breakthrough hepatitis.
Methods:  Effects of entecavir were evaluated in 19 patients who had developed breakthrough hepatitis during lamivudine therapy for longer than 5 years. This study is a subgroup analysis of a previously reported study. Entecavir, in either 0.5 or 1.0 mg/day doses, was given to 10 and nine patients for 52 weeks, respectively, and then all received 1.0 mg/day entecavir for an additional 68–92 weeks.
Results:  There were no differences in biochemical and virological responses in the two groups of patients with respect to the two different initial doses of entecavir. Serum levels of alanine aminotransferase were normalized in 17 (90%) patients, and hepatitis B e antigen (HBeAg) disappeared from the serum in two (14%) of the 14 patients who were HBeAg-positive before. Furthermore, a decrease in histological activity index score greater than 2 points was achieved in nine of the 11 (82%) patients in whom annual liver biopsies were performed during 3 years while they received entecavir. HBV mutants resistant to entecavir emerged in five of the 19 (26%) patients, and hepatitis flare occurred in two of them (40%).
Conclusion:  Entecavir in the long term would be useful for histological improvement of breakthrough hepatitis induced by lamivudine-resistant HBV mutants in patients with chronic hepatitis B. However, the relatively high rate of entecavir resistance is a concern, and other strategies need to be considered when available.