AASLD2012:恩替治疗过程中ALT升高是有利的

StephenW

恩替卡韦治疗过程中的ALT flare是有利的
CONTROL ID: 1415364
PRESENTATION TYPE: Oral or Poster
CURRENT CATEGORY: Hepatitis B
CURRENT DESCRIPTORS: I02. Treatment and Clinical Trials
TITLE: ALT flares during entecavir treatment are associated with a favorable outcome in chronic hepatitis B
AUTHORS (FIRST NAME, LAST NAME): Roeland Zoutendijk1, Jurrien G. Reijnders1, Fabien Zoulim2, Ashley S. Brown3, David J. Mutimer4, Katja Deterding5, Wolf P. Hofmann6, Joerg Petersen7, Massimo Fasano8, Maria Buti9, Thomas Berg10, Milan J. Sonneveld1, Bettina E. Hansen1, Heiner Wedemeyer5, Harry L. Janssen1
Institutional Author(s):
INSTITUTIONS (ALL): 1. Erasmus MC, Rotterdam, Netherlands.
2. Hospices Civils de Lyon, Lyon, France.
3. Imperial College, London, United Kingdom.
4. Queen Elizabeth Hospital, Birmingham, United Kingdom.
5. Medical School Hannover, Hannover, Germany.
6. Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
7. Asklepios Klinik St. Georg, Hamburg, Germany.
8. University of Bari, Bari, Italy.
9. Hospital Vall de Hebron, Barcelona, Spain.
10. University Clinic of Leipzig, Leipzig, Germany.
ABSTRACT BODY: Background Elevations of ALT or flares during nucleos(t)ide analogue therapy are usually associated with antiviral resistance or cessation of therapy. Since entecavir (ETV) resistance is rare and therapy is rarely stopped, we aimed to investigate the frequency and outcome of on-treatment flares during ETV therapy in chronic HBV patients.
Methods Within this investigator-initiated project we studied all HBV monoinfected patients treated with ETV monotherapy from 10 large European referral centers (VIRGIL Study Group). A flare was defined as an ALT >3x level at start of ETV therapy (Flink et al, Gut 2005). ALT was measured locally using automated techniques, HBV DNA undetectability was defined as HBV DNA <80 IU/mL.
Results A total of 366 patients were treated for a median of 19 (range 3-51) months with ETV monotherapy. Eleven (3%) patients developed a flare after a median of 6 (1-25) months, resulting in an incidence of 0.017 flares per ETV treatment year. The flares were relatively mild with a mean ALT peak of 7.3±4.0 xULN. Patients with a flare were more often HBeAg+ (73%, p=0.03). Other baseline characteristics (including ALT) were comparable between patients developing a flare and those not. Five (45%) patients had an ALT flare associated with a favorable event: 4 had an ALT flare accompanied by a vigorous early (week 4) HBV DNA decline and 1 patient achieved HBeAg seroconversion (flare at month 6). Three (27%) patients had a flare (month 3, 7 and 23) associated with an increase in viral load caused by non-compliance and one possibly associated with development of HCC (month 25). In 2 (18%) patients no clear association of the flare could be established. Importantly, both biochemical and virological outcome after the flares was good: 9 patients achieved ALT normalization (82%) and 10 achieved HBV DNA undetectability (91%) without treatment adaptation.
Conclusion Flares during ETV are rare and relatively mild. The majority of flares are associated with either a vigorous decline or an increase in HBV DNA caused by non-compliance, underlining the importance of these measurements to interpret flares. After reassuring compliance and excluding other causes, ETV therapy can confidently be continued as the majority of flares have a good biochemical- and virological outcome and resolve without treatment adaptation.

StephenW

背景
ALT升高或核苷（酸）类似物治疗期间flare通常与抗病毒药物耐药或停止治疗。由于恩替卡韦（ETV）的耐药是罕见的，很少停止治疗，我们的目的是调查的频率和结果ETV治疗慢性乙型肝炎患者对治疗的flare。
研究者发起的项目中的方法，我们研究了所有从欧洲10大转介中心（VIRGIL研究组）与ETV单药治疗HBV monoinfected患者。flare被定义为ALT> 3倍水平开始ETV治疗弗林克等人（2005年），肠道。 ALT测定在本地使用自动化技术，被定义为HBV DNA不可检测HBV DNA <80 IU / mL的。
结果共366例患者治疗中位数为19个月（范围3-51）与ETV单药治疗。 11例（3％）患者flare后的中位数为6个月（1-25），导致的发病率0.017flare每ETV治疗一年。的flare相对温和，平均ALT峰值7.3±4.0 xULN的。更经常flare患者HBeAg阳性+（73％，P = 0.03）。其他基线特征（包括ALT）的发展flare和那些没有患者之间的相媲美。 5（45％）患者的ALTflare一个有利的事件相关联：4 ALTflare伴随着一场轰轰烈烈的早期（第4周）HBV DNA下降，1例患者实现HBeAg血清学转换（flare在6个月）。三例患者（27％）与病毒载量的增加所造成的非合规性和可能与肝癌的发生（月25日）flare（3月7日和23）。在2例患者（18％）的flare可建立没有明确的关联。更重要的是，生物化学和病毒学flare后的结果是好的：9例患者达到ALT正常化（82％）和10个实现HBV DNA不可检测性（91％）未经治疗的适应。
ETV
结论flare是罕见的，相对温和。一场轰轰烈烈的下降或增加HBV DNA所造成的不遵守这些测量的重要性，强调的解释flare与大多数的flare。令人欣慰的合规性和排除其他原因后，ETV治疗可以放心地继续，因为大部分的flare有很好的生化和病毒学结果和解决未经处理的适应。