恩替卡韦联合六味五灵片治疗乙型肝炎病毒e抗原阳性慢性乙型肝炎的临床观察

目的探讨恩替韦卡（ETV）联合六味五灵片治疗乙型肝炎病毒e抗原阳性慢性乙型肝炎的疗效和安全性。方法将124例乙型肝炎病毒e抗原阳性慢性乙型肝炎患者采用随机数字表法分为两组,分别采用ETV联合六味五灵片治疗和单纯ETV治疗,比较两组肝功能及病毒复制指标。结果观察组有效率91．94％,对照组有效率82．26％,两组差异有统计学意义（Ridit=32．251,P〈0．05）;治疗24周、48周,观察组HBVDNA低于对照组,差异有统计学意义（t=2．365、4．595,均P〈0．05）;治疗后,观察组ALT、AST下降程度显著大于对照组（t=78．512、62．145,均P〈0．05）;治疗后两组ALT复常率、总有效率和反跳率差异均有统计学意义（x^2=25．621、46．241、11．512,均P〈0．05）,HBVDNA和HBeAg阳性低于检测下限例数差异具有统计学意义（x^2=17．265、21．264,均P〈0．05）。结论恩替韦卡联合六味五灵片治疗乙型肝炎病毒e抗原阳性慢性乙型肝炎能够减轻肝脏纤维化．并具有明显解毒和抗病毒作用。     

阿德福韦酯应答不佳的慢性乙型肝炎患者加用恩替卡韦进行优化治疗的临床研究

目的分析阿德福韦酯应答不佳的E抗原（HBeAg）阳性慢性乙型肝炎患者加用恩替卡韦进行联合治疗的疗效。方法阿德福韦酯治疗1年而乙型肝炎病毒脱氧核糖核酸（HBV DNA）仍阳性的慢性乙型肝炎患者被纳入,采用阿德福韦酯联合恩替卡韦治疗作为优化治疗策略。结果共纳入25例患者,本组患者在治疗3个月和6个月时均取得了较好的应答率;在联合治疗开始后的第3个月和第6个月,HBV DNA阴转率分别达到64%（16/25）和92%（23/25）,丙氨酸氨基转移酶（ALT）复常率分别达到72%（18/25）和96%（24/25）,HBeAg消失率分别是8%（2/25）和24%（6/25）,HBeAg/Anti-HBe血清学转换率分别是4%（1/25）和12%（3/25）。在头6个月的联合治疗期内,患者耐受良好,所有患者均未发生任何严重不良事件。结论阿德福韦酯应答不佳的慢性乙型肝炎患者,采用恩替卡韦联合阿德福韦酯进行优化治疗可获得较好的疗效。     

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。     

恩替卡韦治疗33例乙肝肝硬化失代偿期疗效观察

目的：观察恩替卡韦治疗乙肝后肝硬化失代偿期的临床疗效。方法：对我院2010年2月～2012年2月收治的33例乙肝后肝硬化失代偿期患者采用口服恩替卡韦治疗,每天给药0．5mg,每天1次,观察为48周,比较患者治疗前后的生化、纤维化指标、HBV～DNA定量变化。结果：经过48周的治疗后,患者的ALT、AST较治疗前相比,均得到明显改善（P〈0．05）,HBV～DNA水平较治疗前明显下降（P〈0．05）。结论：恩替卡韦能够快速抑制病毒复制,改善肝功能,且安全性较好,在一定程度上可逆转肝硬化。     

恩替卡韦对失代偿期乙型肝炎肝硬化患者肝功能及血清病毒学指标的影响

目的：观察恩替卡韦治疗失代偿期乙型肝炎肝硬化患者72周内肝功能及血清病毒学指标的变化。方法将失代偿期乙型肝炎肝硬化患者92例按随机数字表法分为试验组和对照组,各46例,对照组常规内科治疗,试验组在常规治疗基础上加用恩替卡韦片。比较两组12、24、48、72周时肝功能指标、血清病毒学指标及Child‐Pugh评分,并观察患者临床结局。结果随治疗时间的延长,试验组丙氨酸氨基转移酶（ALT）、总胆红素（TBiL）值和Child‐Pugh评分逐渐降低,差异有统计学意义（P＜0.05或 P＜0.01）,白蛋白（ALB）和凝血酶原活动度（PTA）值逐渐升高,差异有统计学意义（P＜0.01）。治疗后同一时段,试验组ALT、TBiL值和Child‐Pugh评分低于对照组（P＜0.01）;ALB和 PTA 值高于对照组,差异有统计学意义（P＜0.01）。随治疗时间的延长,试验组HBV DNA值逐渐降低（P＜0.01）,同一时段明显低于对照组,差异有统计学意义（P＜0.01）。72周时,试验组HBV DNA＜500 copies／mL者的比例、HBeAg阴转率、HBeAg／抗‐HBe血清学阴转率均明显高于对照组,差异有统计学意义（P＜0.05或 P＜0.01）。试验组和对照组 Child‐Pugh C 级患者死亡分别为3例（6.52％）和4例（8.70％）,两组病死率比较差异无统计学意义（ P＞0.05）。结论恩替卡韦有助于改善失代偿期乙型肝炎肝硬化患者的肝功能,抑制HBV复制,提高 HBeAg阴转率。     

Asociación Mexicana de Hepatología A.C. Guía Clínica de Hepatitis B

Hepatitis B virus (HBV) infection continues to be a worldwide public health problem. In Mexico, at least three million adults are estimated to have acquired hepatitis B (total hepatitis B core antibody [anti-HBc]-positive), and of those, 300,000 active carriers (hepatitis B surface antigen [HBsAg]-positive) could require treatment. Because HBV is preventable through vaccination, its universal application should be emphasized. HBV infection is a major risk factor for developing hepatocellular carcinoma. Semi-annual liver ultrasound and serum alpha-fetoprotein testing favor early detection of that cancer and should be carried out in all patients with chronic HBV infection, regardless of the presence of advanced fibrosis or cirrhosis. Currently, nucleoside/nucleotide analogues that have a high barrier to resistance are the first-line therapies.     

肝达康胶囊联合恩替卡韦治疗慢性乙型肝炎的临床研究

目的 探讨肝达康胶囊联合恩替卡韦治疗慢性乙型肝炎的临床疗效。方法 选取2018年1月-2019年6月于新乡医学院第一附属医院感染科就诊的124例慢性乙型肝炎患者,随机分为对照组和治疗组,每组各62例。对照组口服马来酸恩替卡韦片,1片/次,1次/d。治疗组在对照组治疗的基础上口服肝达康胶囊,8粒/次,3次/d。两组均连续治疗3个月。观察两组的临床疗效,比较两组治疗前后肝功能指标、肝纤维化指标、Th1和Th2细胞百分比和细胞因子水平的变化情况。结果 治疗后,治疗组和对照组的总有效率分别是95.16%、82.26%（P<0.05）。治疗后,两组患者血清丙氨酸氨基转氨酶（ALT）和天门冬氨酸氨基转移酶（AST）同各组治疗前相比均显著降低（P<0.05）;与对照组相比,治疗后治疗组患者血清ALT和AST水平降低更加明显（P<0.05）。治疗后两组患者血清层黏连蛋白（LN）、透明质酸（HA）、Ⅲ型前胶原N端肽（PCIII）、Ⅳ型胶原（IV-C）水平均明显下降（P<0.05）;且治疗后治疗组上述指标同对照组相比降低更加明显（P<0.05）。治疗后,两组Th1、Th1/Th2显著降低,而Th2显著升高（P<0.05）;与对照组相比,治疗后治疗组Th1、Th1/Th2显著更低,而Th2显著更高（P<0.05）。治疗后,两组患者γ干扰素（IFN-γ）、肿瘤坏死因子α（TNF-α）水平均显著下降,而白细胞介素4（IL-4）、白细胞介素6（IL-6）水平均显著升高（P<0.05）;治疗后,治疗组患者IFN-γ、TNF-α水平低于对照组,而IL-4、IL-6水平高于对照组（P<0.05）。结论 肝达康胶囊联合恩替卡韦治疗慢性乙型肝炎具有较好的临床疗效,能显著改善患者肝脏损伤情况,可能与改善Th1/Th2细胞失衡有关,具有一定的临床推广应用价值。     

聚乙二醇干扰素alpha-2a联合恩替卡韦治疗高病毒载量HBeAg阳性慢性乙型肝炎的临床研究

目的 观察聚乙二醇干扰素alpha-2a联合恩替卡韦治疗高病毒载量HBeAg阳性慢性乙型肝炎的疗效及安全性.方法 60例HBeAg阳性患者随机分成三组:聚乙二醇干扰素α-2a组20例(A组),恩替卡韦组20例(B组),聚乙二醇干扰素联合恩替卡韦组20例(C组)(联合治疗12周后单用聚乙二醇干扰素治疗).观察三组患者治疗4、12及24周时丙氨酸氨基转移酶(ALT)复常率、HBV DNA阴转率、HBsAg和HBeAg血清转换情况,并观察其不良反应.结果 分别在治疗第4、12、24周时比较三组,A组、B组的HBV DNA阴转率均明显低于C组(分别为:Z=-4.6,P＜0.0001;Z=-2.53,P=0.0114);A组ALT复常率明显低于C组(Z=-2.63,P=0.0086),B组与C组的ALT复常率差异无统计学意义;C组的HBsAg、HBeAg下降幅度大于A组和B组.结论 聚乙二醇干扰素alpha-2a联合恩替卡韦治疗高病毒载量HBeAg阳性慢性乙型肝炎患者,6个月疗程中HBV DNA阴转率、ALT复常率均优于聚乙二醇干扰素单药治疗,且安全性良好.     

Efficacy of Entecavir Treatment for up to 5 Years in Nucleos(t)ide-Na?ve Chronic Hepatitis B Patients in Real Life

Objective: To analyze the efficacy and safety of entecavir (ETV) treatment for up to 5 years in nucleos(t)ide-naïve chronic hepatitis B patients in real life.Methods: We retrospectively analyzed 230 nucleos(t)ide naïve chronic hepatitis B patients who received ETV 0.5 mg/day monotherapy for at least 3 months, of whom 113 were HBeAg positive and 117 were HBeAg negative. The primary endpoints was cumulative probability of achieving a virological response (undetectable serum HBV DNA, <100IU/mL). Secondary endpoints were rates of ALT normalization (ALT < upper limit of normal), HBeAg seroconversion, resistance, and safety.Results: The median follow-up duration was 27.5 months (3-73 months) and mean age was 42 years. With 230, 214, 180, 142, 88, 42 and 11 patients followed-up for at least 3 months,6 months, 1, 2, 3, 4 and 5 years, respectively. In all, Incremental increases were observed in the rates of undetectable HBV DNA. 67.0%, 85.0%, 89.4%, 94.4%, 95.5%, 97.6%, 100% had undetectable HBV DNA at month 3, month 6, 1 year, 2 years, 3 years, 4 years and 5 years. Proportions of patients achieving normal ALT were 73.9%, 85.5%, 82.8%, 89.4%, 80.7%, 85.7%, 100%, respectively. The rate of HBeAg seroconversion reached 21.4% and 15.4% at year2, 3, respectively. One patient achieved HBsAg seroclearance after 1 year, and achieved anti-HBs seroconversion at year 3. Of 180 patients, HBV DNA was detectable (partial virological response, PVR) in 19 patients at year 1 of follow-up, twelve of 14 (85.7%) patients with PVR need more than 1 year of continuous ETV therapy to achieved VR. At baseline, no ETV-resistance was detected in 25 ETV-naïve patients. One patient developed ETV-resistance mutations due to noncompliance. No serious adverse event was reported.Conclusion: Long-term ETV treatment of nucleos(t)ide-naïve was effective and safe in real life. Adjustment of ETV monotherapy in nucleos(t)ide-naïve patients with a partial virological response at 1 year may be unnecessary.