替诺福韦抢救治疗经过多次治疗失败的慢性乙型肝炎患者

StephenW

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3531685/
World J Gastroenterol. 2012 December 21; 18(47): 6996–7002. Published online 2012 December 21.   doi:  10.3748/wjg.v18.i47.6996
PMCID: PMC3531685

Tenofovir rescue therapy for chronic hepatitis B patients after multiple treatment failures替诺福韦抢救治疗经过多次治疗失败的慢性乙型肝炎患者
Yu Jin Kim, Dong Hyun Sinn, Geum-Youn Gwak, Moon Seok Choi, Kwang Cheol Koh, Seung Woon Paik, Byung Chul Yoo, and  Joon Hyeok Lee

Abstract

AIM: To evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) for chronic hepatitis B (CHB) patients after multiple failures.

METHODS: A total of 29 CHB patients who had a suboptimal response or developed resistance to two or more previous nucleoside/nucleotide analogue (NA) treatments were included. Study subjects were treated with TDF alone (n = 13) or in combination with lamivudine (LAM, n = 12) or entecavir (ETV, n = 4) for ≥ 6 mo. Complete virologic response (CVR) was defined as an achievement of serum hepatitis B virus (HBV) DNA level ≤ 60 IU/mL by real-time polymerase chain reaction method during treatment. Safety assessment was based on serum creatinine and phosphorus level. Eleven patients had histories of LAM and adefovir dipivoxil (ADV) treatment and 18 patients were exposed to LAM, ADV, and ETV. Twenty-seven patients (93.1%) were hepatitis B e antigen (HBeAg) positive and the mean value of the baseline serum HBV DNA level was 5.5 log IU/mL ± 1.7 log IU/mL. The median treatment duration was 16 mo (range 7 to 29 mo).

RESULTS: All the patients had been treated with LAM and developed genotypic and phenotypic resistance to it. Resistance to ADV was present in 7 patients and 10 subjects had a resistance to ETV. One patient had a resistance to both ADV and ETV. The cumulative probabilities of CVR at 12 and 24 mo of TDF containing treatment regimen calculated by the Kaplan Meier method were 86.2% and 96.6%, respectively. Although one patient failed to achieve CVR, serum HBV DNA level decreased by 3.9 log IU/mL from the baseline and the last serum HBV DNA level during treatment was 85 IU/mL, achieving near CVR. No patients in this study showed viral breakthrough or primary non-response during the follow-up period. The cumulative probability of HBeAg clearance in the 27 HBeAg positive patients was 7.4%, 12%, and 27% at 6, 12, and 18 mo of treatment, respectively. Treatment efficacy of TDF containing regimen was not statistically different according to the presence of specific HBV mutations. History of prior exposure to specific antiviral agents did not make a difference to treatment outcome. Treatment efficacy of TDF was not affected by combination therapy with LAM or ETV. No patient developed renal toxicity and no cases of hypophosphatemia associated with TDF therapy were observed. There were no other adverse events related to TDF therapy observed in the study subjects.

CONCLUSION: TDF can be an effective and safe rescue therapy in CHB patients after multiple NA therapy failures.

StephenW

目的：观察富马酸替诺福韦酯（TDF）经过多次失败的慢性乙型肝炎（CHB）患者的疗效和安全性。

方法：将29例慢性乙型肝炎患者的反应欠佳，或产生抗药性的治疗包括两个或多个先前的核苷/核苷酸类似物（NA）。研究的受试者接受TDF组（n = 13）单独或联合拉米夫定（LAM，N = 12）或恩替卡韦（ETV，N = 4）≥6个月。血清乙型肝炎病毒（HBV）DNA水平的成就被定义为≤60 IU / ml的实时聚合酶链反应方法在治疗过程中完全病毒学应答（CVR）。安全评估是基于血清肌酐，磷水平。 11个病人有暴露史林和阿德福韦酯（ADV）治疗，18例LAM，ADV，ETV。 27例（93.1％），乙型肝炎e抗原（HBeAg）阳性和基线血清HBV DNA水平的平均值为5.5日志IU / mL的±1.7日志IU /毫升。平均治疗时间为16个月（范围为7至29个月）。

结果：所有患者经治疗后已与林和开发的基因型和表型耐药。耐ADV 7例，10个科目的电阻ETV。一个病人有抗ADV和ETV。 CVR在12和24个月的TDF含治疗方案，采用Kaplan Meier法计算累积概率分别为86.2％和96.6％。虽然未能实现CVR一个病人，血清HBV DNA水平下降了3.9日志IU / mL的从基线和在治疗过程中的最后一个血清HBV DNA水平为85国际单位/毫升，达到近CVR。在随访期间，无一例患者在这项研究中表明病毒突破或主要非响应。在27 HBeAg阳性患者的HBeAg清除的累积概率，分别为7.4％，12％，27％，6，12，和18个月的治疗。 TDF含方案治疗效果的差异无统计学根据特定的HBV突变的存在。历史的前暴露于特定的抗病毒药物没有作出处理结果的差异。 LAM或ETV联合治疗的TDF治疗的效果并没有受到影响。没有病人出现肾毒性，并没有发生低磷血症与TDF治疗观察。目前还没有其他不良事件相关的TDF治疗观察研究对象。

结论：TDF可以在多个NA治疗失败后的慢性乙型肝炎患者的抢救治疗是有效和安全的。

lifevendor

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Hello Stephen!

StephenW

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How are you? Keeping well, I hope.

lifevendor

StephenW 发表于 2013-1-29 17:46
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How are you? Keeping well, I hope.

I am back in forum  to updating my database of HBV in my brain.

StephenW

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I was watching videos from the recent Paris Conference, the Chairman (Patrick Marcellan) summary was:
HBV control: yes, cure:?
qHBsAg should combine with hbvdna to predict and tailor treatment.
New treatment: PegIFN + NUCs
New drug: Lambda IFN, TLR7 agonist,?