恩替卡韦与阿德福韦酯抑制乙型肝炎调节性T细胞的效价差异

目的:比较恩替卡韦(ETV)与阿德福韦酯(ADV)在抑制慢性乙型肝炎(CHB)患者调节性T细胞(Treg)效价的差异。方法:收集36例CHB患者随机分为ETV及ADV组,分别给予口服ETV 0.5 mg q.d.及ADV 10 mg q.d.;治疗48周,分别于第12、24、36及48周采血检测Treg的含量,使用定量PCR检测其功能因子叉头蛋白p3(Foxp3)mRNA含量,用ELISA检测其细胞因子白介素10(IL-10)及转化生长因子β1(TGF-β1)的含量,并检测乙肝病毒定量(HBVDNA)、肝功能。结果:治疗前两组患者上述指标均不存在统计学差异(P>0.05);治疗后第24、36及48周ETV组Treg含量均显著低于ADV组(P<0.05);ETV组第12、36及48周的Foxp3均低于ADV组;ETV组第48周的IL-10含量低于ADV;ETV组第36及48周的TGF-β1含量低于ADV组(P<0.05);ETV组第12及36周的HBV DNA低于ADV组,且第48周两组的HBV DNA均已降至1000 copies/mL的参考值以内;第12周ETV组的ALT显著低于ADV组,ETV组其余时间点的ALT以及总胆红素均与ADV组不存在统计学差异;相关性分析显示Treg与HBV DNA呈显著正相关性(r=0.785,P=0.016)。结论:在抗HBV效价相当的情况下,ETV抑制调节性T细胞的效价优于ADV。     

恩替卡韦对慢性乙型肝炎患者外周血B淋巴细胞亚群的影响

目的探讨恩替卡韦抗病毒治疗对慢性乙型肝炎患者外周血B淋巴细胞亚群的影响。方法慢性乙型肝炎患者60例,随机分为对照组、治疗组各30例。对照组仅给予常规治疗,治疗组另外给予恩替卡韦0.5 mg/d,口服,疗程48周。检测治疗前后患者外周血CD5+B细胞(CD5+,CD19+)及传统B细胞(CD5-,CD19+)百分率。结果对照组治疗前后外周血CD5+B淋巴细胞百分率无明显变化,治疗组治疗后较治疗前明显下降,且明显低于对照组(P<0.05)。结论恩替卡韦治疗对于慢性乙型肝炎患者体液免疫失衡有改善作用。     

恩替卡韦在治疗乙型肝炎病毒相关肝病中的应用

恩替卡韦(entecavir,ETV)是新一代核苷酸类抗病毒药物,具有强效抗病毒作用和极低耐药性的特点,被广泛用于治疗乙型肝炎病毒(hepatitis B virus,HBV)相关的慢性肝炎、肝硬化和急慢性重型肝炎等疾病.此文就ETV在HBV相关肝病的临床治疗中的应用作一综述.     

恩替卡韦治疗慢性重型乙型肝炎早期患者的疗效分析

目的探讨恩替卡韦治疗慢性重型乙型肝炎早期患者的疗效。方法选取2010年6月～2011年9月我院收集的慢性重型乙型肝炎患者50例,将其随机分为治疗组和对照组,各25例。对照组给予内科综合治疗,治疗组在此基础上给予口服恩替卡韦0.5 mg治疗,1次/d。记录两组治疗前及治疗后4、8、12周的肝功能酶、凝血酶原时间及血清HBV DNA水平,并观察两组的疗效。结果治疗组和对照组治疗前肝功能、凝血酶原时间,HBV DNA水平比较,差异均无统计学意义（P〉0.05）,治疗后4、8、12周肝功能、凝血酶原时间及治疗后4、8周HBV DNA水平比较,差异均有统计学意义（P〈0.05、P〈0.01）。治疗后12周两组HBV DNA载量水平均低于检测值（103拷贝/mL）,其所占比例（100%、24%）比较,差异有统计学意义（P〈0.05）。治疗后12周,治疗组病情好转率[96%（24/25）]高于对照组[60%（15/25）]（P〈0.05）。治疗过程中患者并未出现与恩卡替韦相关的不良反应,且耐受性较好。结论恩替卡韦治疗慢性重型乙型肝炎早期效果好且比较安全,可显著改善患者的病情,提高生存率,值得推广应用。     

拉米夫定和阿德福韦酯初始联合治疗慢性乙型肝炎的临床研究

目的观察拉米夫定（LAM）和阿德福韦酯（ADV）初始联合治疗与恩替卡韦（ETV）单药治疗慢性乙型肝炎的疗效。方法选择我院2008年7月～2010年6月符合抗病毒治疗的未曾使用过核苷（酸）类似物的初治慢性乙型肝炎患者334例,分为联合组192例,单药组142例,联合组应用LAM 100 mg,ADV 10 mg,每日1次,单药组应用ETV0.5 mg,每日1次。分别在基线,12、24、36、48、72、96周时留取血清,采用化学发光法定量检测HBsAg和HBeAg,采用实时荧光定量聚合酶链反应（PCR）检测HBV DNA水平,采用PCR产物直接测序法检测病毒耐药基因。结果①两组在治疗12周和24、36、48周时时,HBV DNA〈500拷贝/mL的比率,差异无统计学意义（P〉0.05）。②治疗72周和96周时,HBV DNA〈500拷贝/mL的比率,联合组分别为77%、78%,单药组分别为77%、76%,两组比较差异有统计学意义（均P〈0.05）。③治疗96周时,联合组未见病毒学突破和耐药发生,而单药组检测到1例恩替卡韦相关耐药基因变异位点。结论 LAM和ADV初始联合治疗,在减少病毒学突破和耐药发生及长期疗效发面优于ETV单药治疗。     

恩替卡韦联合复方丹参滴丸治疗慢性乙型肝炎肝纤维化的临床研究

目的：观察恩替卡韦联合复方丹参滴丸治疗慢性乙型肝炎肝纤维化的临床疗效。方法：60例乙肝肝纤维化患者,随机分为两组,联合治疗组给予复方丹参滴丸和恩替卡韦治疗,对照组只给予恩替卡韦治疗,疗程均为6个月。观察治疗后两组HBV-DNA及肝纤维化指标（HA、LN、PCⅢ、CⅣ）变化情况。结果：治疗后两组血清HBV—DNA、肝纤维化指标较治疗前均明显下降,治疗组肝纤维化指标明显低于对照组（P〈0．01）。结论：恩替卡韦联合复方丹参滴丸即能有效抑制乙肝病毒复制,同时可以明显改善慢性乙型肝炎肝纤维化指标。     

Telbivudine： A new treatment for chronic hepatitis B

Three hundred and fifty million people worldwide are estimated to be chronically infected with hepatitis B virus. 15%-40% of these subjects will develop cirrhosis, liver failure or hepatocellular carcinoma during their life. The treatment of chronic hepatitis B has improved dramatically over the last decade merits to the advent of nucleoside/nucleotide analogues and the use of pegylated interferons. Approved drugs for chronic hepatitis B treatment include： standard interferon- alpha 2b, pegylated interferon-alpha 2a, lamivudine, adefovir dipivoxil, and entecavir. Unfortunately, these agents are not effective in all patients and are associated with distinct side effects. Interferons have numerous side effects and nucleoside or nucleotide analogues, which are well tolerated, need to be used for prolonged periods, even indefinitely. However, prolonged treatment with nucleoside or nucleotide analogues is associated with a high rate of resistance. Telbivudine is a novel, orally administered nucleoside analogue for use in the treatment of chronic hepatitis B. In contrast to other nucleoside analogues, Telbivudine has not been associated with inhibition of mammalian DNA polymerase with mitochondrial toxicity. Telbivudine has demonstrated potent activity against hepatitis B with a significantly higher rate of response and superior viral suppression compared with lamivudine, the standard treatment. Telbivudine has been generally well tolerated, with a low adverse effect profile, and at its effective dose, no dose- limiting toxicity has been observed. Telbivudine is one of the most potent antiviral agents for chronic hepatitis B virus and was approved by the FDA in late 2006.     

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.     

3种方案治疗慢性乙型肝炎YMDD变异的成本-效果分析

目的:评价3种方案治疗慢性乙型肝炎YMDD变异患者的成本-效果。方法:将90例患者随机分为3组,A组采用阿德福韦酯与拉米夫定联合治疗12周后,单用阿德福韦酯治疗36周;B组采用阿德福韦酯与拉米夫定联合治疗48周;C组接受恩替卡韦治疗48周。运用药物经济学方法分析其成本-效果。结果:A、B、C组HBV DNA转阴率成本-效果比分别为12685.6、15481.3、31462.2;以A组为参照,B、C组增量成本-效果比为29501.5、106907.8。A、B、C组丙氨酸氨基转移酶复常率成本-效果比分别为12685.6、14284.9、31462.2;以A组为参照,B、C组增量成本-效果比为19618.5、106907.8。A、B、C组HBeAg/HBeAb转换率成本-效果比分别为76227.9、93120.3、209664.0;以A组为参照,B、C组增量成本-效果比为178350.0、1267621.4。A组治疗48周出现rtA181V和rtN236T变异各1例。结论:B组方案为治疗慢性乙型肝炎YMDD变异患者的较优选择。