恩替卡韦序贯聚乙二醇化干扰素-α与单用恩替卡韦治疗慢性乙型肝炎的临床疗效比较:系统评价与分析

 目的 系统评价与分析恩替卡韦(ETV)序贯聚乙二醇化干扰素-α(Peg-IFN-α)与单用ETV在治疗慢性乙型肝炎患者中的临床疗效。方法 计算机检索PubMed、Embase、Cochrane Library、中国知网、万方数据库,搜索有关ETV及ETV序贯Peg-IFN-α治疗慢性乙型肝炎的随机对照试验研究,应用Stata 16.0软件对符合纳入条件的临床研究进行系统评价与分析。结果 共纳入10篇文献,1 250例患者,其中553例患者采用ETV序贯Peg-IFN-α治疗,697例患者单用ETV治疗,两组患者组间基线特征比较,差异均无统计学意义(均P＞0.05)。ETV序贯Peg-IFN-α试验组的HBsAg转换率、HBsAg清除率、HBeAg转换率、HBeAg清除率均高于ETV对照组,差异均有统计学意义(均P＜0.05)。结论 在慢性乙型肝炎抗病毒治疗中,总体上ETV序贯Peg-IFN-α治疗疗效优于单用ETV。     

Synthesis of [14C]‐radiolabelled entecavir

Radiolabelled [¹⁴C]entecavir, ( 1 ), was prepared in 12 steps from (1S,2R,3S,5R)‐3‐(benzyloxy)‐2‐(benzyloxymethyl)‐6‐oxa‐bicyclo[3.1.0]hexane 2 . The chemical yield of [¹⁴C]entecavir was 14% from the epoxide 2 . Introduction of [¹⁴C] radiolabel was achieved by elaboration of 4,5‐diaminopyrimidine 8 with triethyl[¹⁴C]orthoformate to purine derivative 9 . The radiochemical yield of [¹⁴C]entecavir from triethyl[¹⁴C]orthoformate was 11.3%. Radiochemical purity of [¹⁴C]entecavir determined by HPLC was 99.8%. The specific activity of [¹⁴C]entecavir was 108 µCi/mg (29.9 mCi/mmol). Copyright © 2005 John Wiley & Sons, Ltd.     

Nucleos(t)ide analogues for hepatitis B virus: Strategies for long-term success

Nucleoside and nucleotide analogues are potent HBV suppressors, but these agents rarely eradicate HBV. Therefore, the durability of viral response is a problem, and long-term therapy is usually required to ensure maintained HBV suppression. Studies have shown that long-term therapy starting with lamivudine may significantly improve survival, reduce the risk of liver-related major complications, and prevent the development of cirrhosis and HCC in chronic hepatitis B patients. However, drug resistance is a critical challenge during long-term nucleos(t)ide analogue maintenance therapy. The emergence of these mutants is characterized by an increasing level of serum HBV DNA, elevation of ALT level, and even hepatitis flare or decompensation. The prevention and proper management of drug resistance are crucial to ensure long-term success. To start treatment in the right patients at the right time with the right drug is essential in minimizing the problem of drug resistance. Each of these agents has a different profile of resistant mutations. In choosing a direct antiviral agent to initiate therapy, resistance profile is a crucial factor to consider, apart from potency and cost. In the case of drug resistance emerging, timely institution of a drug without cross-resistance may rescue the adverse effects of drug resistance and ensure the long-term success of nucleos(t)ide analogue therapy. To develop strategies for enhancing the therapeutic response and shortening the duration of therapy is an ultimate goal to avoid the problems of drug resistance.⁶⁸

• nucleos(t)ide analogues for hepatitis B virus (HBV) are highly effective in suppressing HBV replication but rarely eliminate the virus

• long-term therapy is usually required

• emergence of drug-resistant HBV mutations is a critical challenge

• to treat the right patient at the right time with the drug with highest genetic barrier to drug resistance is essential to minimize the problem with drug resistance

• the strategy of on-treatment adjustment based on level of suppression of HBV DNA needs to be clarified

• studies are needed to find the optimal combination therapy for both better therapeutic efficacy and less drug resistance

• oral antiviral agents able to attack cccDNA are urgently needed

乙肝肝硬化并发皮下脂膜炎样T细胞淋巴瘤伴噬血细胞综合征的治疗分析

目的 探讨乙肝肝硬化并发皮下脂膜炎样T细胞淋巴瘤(SPTCL)伴噬血细胞综合征(HPS)的临床特征和治疗方法。 方法 回顾性分析2014年8月第二军医大学附属东方肝胆外科医院1例乙肝肝硬化并发SPTCL伴HPS病例的临床资料。 结果 T细胞受体(TCR)表型不同则该病的侵袭性、治疗反应性及预后明显不同,伴HPS者治疗效果不佳,生存期短。 结论 乙肝肝硬化并发SPTCL伴HPS罕见,早期骨髓形态学、病理学、免疫组化及基因重排检测对确诊有重要意义,及早有效控制乙肝病毒尤为重要。早期诊断及治疗对延长患者生存期有重要意义。     

恩替卡韦长疗程后联合或序贯IFNα治疗慢性乙型肝炎的效果与安全性分析

目的探讨经恩替卡韦(ETV)长期治疗,有效抑制HBV DNA后,采取序贯或联合IFNα治疗与单用ETV治疗的疗效与安全性比较。方法收集2013年1月-2015年12月南通大学附属吴江医院门诊和住院的慢性乙型肝炎患者27例,所有患者已经ETV抗病毒治疗3年或以上,HBV DNA阴性,无IFN治疗禁忌证,将纳入患者随机分为3组,每组9例。对照组:继续ETV治疗;序贯组:更换为IFNα序贯治疗;联合组:联合IFNα治疗。检测治疗0、12、24、36、48周时血清HBV DNA、HBV血清标志物、血常规、肝功能,观察治疗情况,记录结果并进行统计分析。计量资料多组间比较采用单因素方差分析,进一步两两比较采用Scheffe检验。结果无退出研究病例,无严重不良事件发生;序贯组有1例24周后出现了病毒反弹,但无临床症状,肝功能各项生化指标正常。治疗结束时,序贯组和联合组HBsAg下降的绝对值均显著高于对照组(P值均<0.001);序贯组和联合组各有2例出现了HBsAg的阴转,阴转率22%;对照组未出现HBsAg的阴转病例。结论 ETV有效抑制病毒复制后的IFNα序贯或联合治疗可能是安全的,HBsAg下降水平优于ETV单药治疗,少数患者出现临床治愈。     

参芪肝康片联合恩替卡韦治疗慢性乙型肝炎的临床研究

目的 探讨参芪肝康片联合恩替卡韦治疗慢性乙型肝炎患者的临床疗效。方法 选取2017年6月—2019年6月于新乡医学院第一附属医院感染科住院治疗的114例慢性乙型肝炎患者作为研究对象,按照住院时间和治疗方式差异随机将患者分为对照组（n=57）和观察组（n=57）。对照组口服抗病毒药物马来酸恩替卡韦片,0.5 mg/次,1次/d。观察组在对照组治疗的基础上口服参芪肝康片治疗,2.1 g/次,3次/d。两组疗程均为6个月。观察两组患者的临床疗效,比较两组治疗前后的肝功能指标、Th17细胞频率、Treg细胞频率、Th17/Treg细胞频率比值、白细胞介素-17（IL-17）、转化生长因子-β（TGF-β）水平以及不良反应发生率。结果 治疗后,对照组和观察组总有效率分别为77.19%和92.98%,两组比较差异具有统计学意义（P<0.05）。与治疗前相比,两组丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆红素（TBIL）水平均显著降低,差异均具有统计学意义（P<0.05）;与对照组相比,观察组治疗后血清ALT、AST和TBIL均显著降低,差异均具有统计学意义（P<0.05）。治疗后,两组患者Th17细胞频率、Th17/Treg细胞频率比值、IL-17水平均显著下降,而Treg细胞频率及TGF-β水平均显著升高（P<0.05）;与对照组相比,治疗后观察组Τh17细胞频率、Th17/Treg细胞频率比值、IL-17水平显著下降,而Treg细胞频率及TGF-β水平均显著升高（P<0.05）。对照组和观察组两组患者不良反应发生率分别为10.53%和14.04%,两组不良反应率相比较无显著差异。结论 参芪肝康片联合恩替卡韦治疗慢性乙型肝炎安全有效,能显著改善肝功能,并降低血清炎症因子水平,可能与影响Th17、Treg细胞频率及降低Th17/Treg细胞频率比值有关。