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与持续增加的丙氨酸转氨酶在慢性乙型肝炎患者接受口腔抗

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才高八斗

发表于 2017-2-22 19:19 |显示全部帖子
Clin Gastroenterol Hepatol. 2017 Feb 12. pii: S1542-3565(17)30149-0. doi: 10.1016/j.cgh.2017.01.032. [Epub ahead of print]
Factors Associated With Persistent Increase in Level of Alanine Aminotransferase in Patients With Chronic Hepatitis B Receiving Oral Antiviral Therapy.Jacobson IM1, Washington MK2, Buti M3, Thompson A4, Afdhal N5, Flisiak R6, Akarca US7, Tchernev KG8, Flaherty JF9, Schall RA9, Myers RP9, Subramanian GM9, McHutchison JG9, Younossi Z10, Marcellin P11, Patel K12.
Author information
  • 1Department of Medicine, Mount Sinai Beth Israel Medical Center, New York, NY, USA. Electronic address: [email protected].
  • 2Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN, USA.
  • 3Servei de Medicina Interna-Hepatologia, Hospital General Universitari Vall d'Hebron, and CIBEREHD del Instituto Carlos III, Barcelona, Spain.
  • 4Hepatology Research, St Vincent's Hospital, Fitzroy, Victoria, Australia.
  • 5Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • 6Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland.
  • 7Department of Gastroenterology, Ege Universitesi Tip Fakultesi, Izmir, Turkey.
  • 8Department of Internal Diseases, Medical University, Sofia, Bulgaria.
  • 9Departments of Clinical Research and Clinical Biometrics, Gilead Sciences, Inc., Foster City, CA, USA.
  • 10Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA.
  • 11Service d'Hépatologie, Viral Hepatitis Research Centre, Hôpital Beaujon, Clichy, France.
  • 12Division of Gastroenterology, Duke Clinical Research Institute and Duke University Medical Center, Durham, NC, USA.


AbstractBACKGROUND & AIM: Despite complete suppression of viral DNA with antiviral agents, in some patients with chronic hepatitis B (CHB), serum levels of alanine aminotransferase (ALT) do not normalize. We investigated factors associated with persistent increases in level of ALT in patients with CHB given long-term tenofovir disoproxil fumarate.
METHODS: We analyzed data from 471 hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with CHB participating in 2 phase 3 trials. We identified patients with an increased level of ALT (above the upper limit of normal range) after 5 years (240 weeks) of tenofovir disoproxil fumarate therapy. We analyzed findings from liver biopsies collected from 467 patients (99%) at baseline and 339 patients (72%) at year 5 of treatment; biopsies were evaluated by an independent pathologist. We performed stepwise, forward, multivariate regression analyses of specified baseline characteristics and on-treatment response parameters to identify factors associated with persistent increases in level of ALT.
RESULTS: Of the 471 patients, 87 (18%) still had an increased level of ALT at year 5 of treatment. Factors independently associated with persistent increase in level of ALT were steatosis score of 5% or more (grade 1 or more) at baseline (odds ratio [OR], 2.224; 95% CI, 1.031-4.852; P=.042) and at year 5 (OR, 3.39; 95% CI 1.560≥7.375; P=.002), HBeAg seropositivity at baseline (OR, 3.30; 95% CI, 1.653-6.576; P<.001), and age of 40 years or more (OR, 2.10; 95% CI, 1.014-4.342; P=.046). Of the 42 HBeAg-positive patients with steatosis at baseline, 21 (50%) had an increased level of ALT at year 5 of treatment. Patients with persistent increases in ALT were more likely to have an increase in steatosis at year 5 than those with a normal level of ALT.
CONCLUSION: HBeAg seropositivity and hepatic steatosis contribute to persistent increases in level of ALT in patients with CHB receiving suppressive antiviral treatment. ClinicalTrials.gov no: NCT00116805.

Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.



KEYWORDS: HBV; adiponutrin/patatin-like phospholipase-3; hepatitis B virus infection; serum transaminase

PMID:28215615DOI:10.1016/j.cgh.2017.01.032

Rank: 8Rank: 8

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62111 元 
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26 
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30441 
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2009-10-5 
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2022-12-28 

才高八斗

发表于 2017-2-22 19:20 |显示全部帖子
Clin Gastroenterol Hepatol。 2017 Feb 12. pii:S1542-3565(17)30149-0。 doi:10.1016 / j.cgh.2017.01.032。 [打印前的电子版]
与持续增加的丙氨酸转氨酶在慢性乙型肝炎患者接受口腔抗病毒治疗相关的因素。
Jacobson IM1,Washington MK2,Buti M3,Thompson A4,Afdhal N5,Flisiak R6,Akarca US7,Tchernev KG8,Flaherty JF9,Schall RA9,Myers RP9,Subramanian GM9,McHutchison JG9,Younossi Z10,Marcellin P11,Patel K12。
作者信息

    1西奈山贝斯以色列医疗中心,纽约,纽约,美国医学部。电子地址:[email protected]
    2病理学,微生物学和免疫学,范德比尔特大学,纳什维尔,TN,美国。
    3Servei de Medicina Interna-Hepatologia,Hospital General Universitari Vall d'Hebron,and CIBEREHD del Instituto Carlos III,Barcelona,Spain。
    4医学研究,圣文森特医院,菲茨罗伊,维多利亚,澳大利亚。
    胃肠病学,Beth以色列女执事医疗中心,波士顿,MA,美国。
    6 Bialystok医学大学传染病与肝病学系,波兰Bialystok。
    7 Eep Universitesi Tip Gakultesi,Izmir,Turkey消化内科。
    8保加利亚索非亚医科大学内部疾病科。
    9临床研究和临床生物学的部门,吉利德科学公司,福斯特城,加利福尼亚州,美国。
    10 Center for Liver Diseases,Department of Medicine,Inova Fairfax Hospital,Falls Church,VA,USA。
    11病毒性肝炎研究中心,HôpitalBeaujon,Clichy,France。
    12Division of Gastroenterology,Duke Clinical Research Institute and Duke University Medical Center,Durham,NC,USA。

抽象
背景技术:

尽管用抗病毒剂完全抑制病毒DNA,但在一些慢性乙型肝炎(CHB)患者中,血清丙氨酸氨基转移酶(ALT)水平不正常化。我们调查了与长期替诺福韦酯对富马酸替诺福韦的CHB患者的ALT水平持续增加相关的因素。
方法:

我们分析了来自471名乙型肝炎e抗原(HBeAg)阳性和HBeAg阴性患者CHB参与2期3试验的数据。我们确定了5年(240周)替诺福韦地索普西延胡索酸盐治疗后ALT水平升高(高于正常范围上限)的患者。我们分析了从基线时467名患者(99%)和治疗第5年339名患者(72%)收集的肝活检样本的结果;活检由独立的病理学家评估。我们对指定的基线特征和治疗反应参数进行逐步,前向,多变量回归分析,以确定与ALT水平持续增加相关的因素。
结果:

在471例患者中,87(18%)在治疗的第5年仍然具有增加的ALT水平。与ALT水平持续增加独立相关的因素是在基线时脂肪变性评分为5%或更高(1级或更高)(优势比[OR],2.224; 95%CI,1.031-4.852; P = 0.042) (OR,3.39; 95%CI1.560≥7.375; P = .002),HBeAg血清阳性在基线(OR,3.30; 95%CI,1.653-6.576; P <.001),年龄40岁或以上(OR,2.10; 95%CI,1.014-4.342; P = 0.046)。在42名患有脂肪变性的HBeAg阳性患者中,21名(50%)在治疗的第5年ALT水平升高。 ALT持续增加的患者在5年时比那些具有正常水平的ALT的患者更可能有脂肪变性增加。
结论:

HBeAg血清阳性和肝脂肪变性有助于持续增加ALT水平的患者CHB接受抑制性抗病毒治疗。 ClinicalTrials.gov no:NCT00116805。

版权所有©2017 AGA Institute。发布者Elsevier Inc.保留所有权利。
关键词:

HBV;脂联素/ patatin样磷脂酶-3;乙型肝炎病毒感染;血清转氨酶

PMID:
    28215615
DOI:
    10.1016 / j.cgh.2017.01.032
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