长期单一疗法和联合治疗在慢性乙型肝炎患者的比较评价：

StephenW

Indian J Med Res. 2016 Sep;144(3):424-432. doi: 10.4103/0971-5916.198674.
Comparative evaluation of long-term monotherapies & combination therapies in patients with chronic hepatitis B: A pilot study.Srivastava M1, Singh N1, Dixit VK1, Nath G2, Jain AK1.
Author information

• 1Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
• 2Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
  

AbstractBACKGROUND & OBJECTIVES: Reduction of viraemia in patients with chronic hepatitis B virus (HBV) infection using nucleoside/nucleotide analogues reduces fatal liver disease-related events, but development of resistance in virus presents serious clinical challenge. Therefore, comparative evaluation of prolonged antiviral monotherapy and combination therapies was prospectively studied to assess their influence on viral suppression, rapidity of response, development of drug resistance and surfacing mutants in chronic liver disease (CLD) patients.
METHODS: A total of 158 (62eAg-ve) chronic hepatitis B patients were prospectively studied for 24 months. Final analysis was performed on patients treated with lamivudine (LAM, n = 28), adefovirdipivoxil (ADV, n = 24), tenofovir disoproxil fumarate (TDF, n = 26), entecavir (ETV, n = 25), LAM + ADV (n = 28) and LAM + TDF (n = 27). Quantitative hepatitis B virus DNA was detected using real-time polymerase chain reaction. Multiple comparisons among drugs and genotypic mutations were analyzed.
RESULTS: Progressive biochemical and virological response were noted with all the regimens at 24 months except LAM and ADV which were associated with viral breakthrough (VBT) in 46.4 and 25 per cent, respectively. Mutations: rtM204V (39.3%), M204V+L180M (10.7%) while rtA181V (8.1%) and rtN236T (8.3%) were observed with LAM and ADV regimen, respectively. LAM + ADV combination therapy revealed VBT in seven per cent of the cases without mutations whereas TDF, ETV and LAM + TDF therapies neither showed VBT nor mutations.
INTERPRETATION & CONCLUSIONS: LAM was the least potent drug among all therapeutic options followed by ADV. TDF and ETV were genetically stable antivirals with a strong efficacy. Among newer combination therapies, LAM + TDF revealed more efficacy in virological remission and acted as a profound genetic barrier on long term. Hence, newer generation molecules (TDF, ETV) and effective combination therapy should be a certain choice.


PMID:28139541DOI:10.4103/0971-5916.198674

StephenW

Indian J Med Res。 2016 Sep; 144（3）：424-432。 doi：10.4103 / 0971-5916.198674。
长期单一疗法和联合治疗在慢性乙型肝炎患者的比较评价：一项试点研究。
Srivastava M1，Singh N1，Dixit VK1，Nath G2，Jain AK1。
作者信息

    1.印度瓦拉纳西Banaras印度大学医学科学研究所消化内科。
    2微生物学，医学科学研究所，巴拿马印度大学，瓦拉纳西，印度。

抽象
背景和目的：

使用核苷/核苷酸类似物减少慢性乙型肝炎病毒（HBV）感染患者的病毒血症减少致命的肝脏疾病相关事件，但是在病毒中发展的耐药性呈现严重的临床挑战。因此，长期抗病毒单一疗法和联合治疗的比较评价进行前瞻性研究，以评估它们对病毒抑制，反应的快速性，耐药性的发展和表面突变体在慢性肝病（CLD）患者中的影响。
方法：

共有158（62eAg-ve）慢性乙型肝炎患者进行前瞻性研究24个月。对于用拉米夫定（LAM，n = 28），阿德福韦酯（ADV，n = 24），富马酸替诺福韦（TDF，n = 26），恩替卡韦（ETV，n = 25），LAM + ADV n = 28）和LAM + TDF（n = 27）。使用实时聚合酶链反应检测定量乙型肝炎病毒DNA。分析了药物之间的多重比较和基因型突变。
结果：

除了LAM和ADV与46.4和25％的病毒性突破（VBT）相关外，所有方案在24个月时注意到进行性生化和病毒学应答。突变：分别用LAM和ADV方案观察到rtM204V（39.3％），M204V + L180M（10.7％），而rtA181V（8.1％）和rtN236T（8.3％ LAM + ADV组合治疗在无突变的情况下显示VBT，而TDF，ETV和LAM + TDF治疗均未显示VBT或突变。
解释与结论：

LAM是所有治疗选择中最有效的药物，其次是ADV。 TDF和ETV是基因稳定的抗病毒药物，具有很强的疗效。在较新的联合治疗中，LAM + TDF显示在病毒学缓解中更有效，并且长期作为深刻的遗传屏障。因此，新一代分子（TDF，ETV）和有效的联合治疗应该是一个选择。

PMID：
    28139541
DOI：
    10.4103 / 0971-5916.198674