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耐药变体出现后肝脏疾病的出现In contrast to interferon-alpha (see below), nucleoside analogues exert aselective pressure on HBV replication that leads to the emergence and expansionof drug-resistant or treatment escape mutants. 不同于干扰素-alpha（见下面），核苷类似物给HBV复制提供了筛选压力，这个压力导致耐药变体或者是治疗逃脱变体的出现。 This has considerable clinical significance.这在临床有非常重要的意义。 The cumulatative prevalence of resistance to Lamivudine and Adefovir over4 years and the other antiviral agents Entecavir, Emtricitabine and Telbivudine over 1–2 yearsis summarised in Table 1. 累加的对拉米夫定和阿德福韦超过4年的耐药情况，还有其他药物恩替卡韦，Emtricitabine和替比夫定超过1到2年的数据被整理在表1.Clinical studies have shown that emergence of Lamivudine- resistant HBVcan be associated with marked viral rebound, increases in serum ALT levels [74] hepatitis flares, and uncommonly,hepatic decompensation and death from liver failure [75,76].临床研究显示拉米夫定的耐药出现可以和病毒的反弹，转氨酶的升高，肝炎暴发，少数情况下肝，失代偿和衰竭死亡联系在一起【75,76】.Persistent infection withLamivudine resistant HBV is associated with blunting of the histological response during years 2 and 3 of treatment and with an increased risk ofhepatic flares with associated increased risk for decompensation in patientswith cirrhosis during years 4 and 5 [75,76].在肝硬化患者第4年和第5年，持久性的被抗拉米夫定乙肝病毒感染并且在第2年和第3年出现迟钝的组织学的（histological）反应，这些可以增加伴随肝失代偿肝炎暴发的风险。[75,76]. In Lamivudine resistant patients who have advanced fibrosis, treatmentconfers only an intermediate level of protective benefit in forestalling disease progression[77]. 在拉米夫定耐药的患者并且有严重的硬化情况下，在先发制人（forstalling）疾病的发展上，治疗可以仅仅达到中级的保护措施[77]。Acute exacerbations of hepatitis are common once Lamivudine resistant HBVemerges as the dominant quasispecies [74] and this is probably because the YMDD/YVDD/YIDDlocus can act as a CD-8C CTL epitope in HLA-A2 positive individuals [78]. Inthe setting of advanced disease, such flares can be fatal [77]. 当拉米夫定耐药株占据主体的时候，急性的肝炎加剧恶化发作（exacerbations：恶化; 激怒; 加剧）经常发现【74】，这可能是在HLA-A2阳性的个体中，因为病毒YMDD / YVDD/ YIDD位点可以作为一个CD 8C CTL的表位 [78]。在一些严重的（advanced）疾病中，这种反弹可能是致命的[77]。Resistance to Adefovir is uncommon in the first two years of therapy butincreases steadily thereafter [79] (see Table 1).阿德福韦的耐药在前两年出现的可能性很低，但是随着年代的增加，耐药出现也上升【79】（见表1）Not as much is known about longer-term effects on disease progression withAdefovir resistant HBV, as patients are usually switched or rescued withanother drug very quickly.阿德福韦耐药HBV病毒的长期效应当前了解并不是很多，因为大部分患者都可以经常的转换或者通过其他的药物快速的得到治疗。In a recent study by Lok and colleagues [80] involving eight patients withAdefovir resistance, HBV DNA levels increased to greater than 5 log10 copies/mlin serum and hepatic decomposition occurred in 2 patients, one of whom died.在近期的一项研究中，Lok和他的同时【80】在一项8个阿德福韦耐药的患者中，血清中HBV DNA的水平升高到大雨5log10 copies/ml，并且2名患者发生肝失代偿，其中一名死亡。All of these patients had pre-existing Lamivudine resistance. 所有这些患者都有拉米夫定耐药。Salvage therapy with Lamivudine, Entecavir or Tenofovir was given to 7patients resulting in a reduction of HBV DNA by greater than 3 log10 copies/mlin 3 patients.通过拉米夫定，恩替卡韦还有提诺富尾给予7名患者补救（salvage）治疗，3名患者HBV DNA的病毒降低了3log10 copies/ml.The main conclusions that have been clearly established over the last 5–6years is that drug-resistant HBV is not a ‘benign or attenuatedvirus’. 过去5到6年时间得到的清晰的主要结论是：耐药的HBV变异体不是“良性的或者是毒性减少的病毒”。 Furthermore, this selection and dominance in drug-treated patients isassociated with disease progression and the benefits initially obtained with drugtreatment in the first phase are quickly lost when resistance emerges [46,76]. 此外，在药物治疗的患者身上，这种病毒的筛选到变为主导和疾病的发展相关，早期药物治疗得到的好处马上被病毒的反弹而消失【46,76】。 | 
发表于 2011-6-5 10:41
出自維基百科，自由嘅百科全書
