基线维生素D水平与慢性乙型肝炎临床指标和治疗结果

StephenW

Research Article
Association of baseline vitamin D levels with clinical parameters and treatment outcomes in chronic hepatitis B

    Henry Lik-Yuen Chan1, , Magdy Elkhashab2, Huy Trinh3, Won Young Tak4, Xiaoli Ma5, Wan-Long Chuang6, Yoon Jun Kim7, Eduardo B. Martins8, Lanjia Lin8, Phillip Dinh8, Prista Charuworn8, Graham R. Foster9, Patrick Marcellin10

    1 Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong
    2 Toronto Liver Centre, Toronto, Ontario, Canada
    3 San Jose Gastroenterology, San Jose, CA, USA
    4 Kyungpook National University Hospital, Daegu, South Korea
    5 Drexel University College of Medicine, Philadelphia, PA, USA
    6 Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
    7 Seoul National University Hospital, Seoul, South Korea
    8 Gilead Sciences, Inc, Foster City, CA, USA
    9 Queen Mary University of London, London, United Kingdom
    10 Hôpital Beaujon, University of Paris, Paris, France

    Received 27 February 2015, Revised 11 June 2015, Accepted 22 June 2015, Available online 2 July 2015


Background & Aims

The relationship between vitamin D levels and chronic hepatitis B (CHB) infection and treatment outcomes are poorly elucidated. We measured pre-treatment serum vitamin D (25-hydroxyvitamin D3; 25[OH]D3) levels and determined their association with clinical parameters and treatment outcomes in active CHB patients without advanced liver disease enrolled in a global clinical trial.
Methods

Patients were randomly assigned to either 48 weeks of tenofovir disoproxil fumarate (TDF) plus peginterferon alfa-2a (PegIFN), TDF plus PegIFN for 16 weeks followed by TDF for 32 weeks, PegIFN for 48 weeks, or TDF for 120 weeks. Univariate and multivariate analyses were conducted to determine associations between vitamin D, baseline factors, and week 48 clinical outcome.
Results

Of 737 patients, 35% had insufficient (⩾20 but <31 ng/ml) and 58% had deficient (<20 ng/ml) vitamin D levels. In univariate analysis, lower vitamin D levels were significantly associated with the following baseline parameters: younger age, lower uric acid levels, HBeAg-positive status, lower calcium levels, blood draw in winter or autumn, and HBV genotype D. On multivariate analysis, only HBV genotype, season of blood draw, calcium level, and age retained their association. High baseline level of vitamin D was associated with low HBV DNA, normal ALT and HBsAg at week 48 independent of treatment groups, but the association, with the exception of ALT, became statistically insignificant after adjusting for age, gender, HBeAg and HBV genotype.
Conclusions

Abnormally low vitamin D levels are highly prevalent among untreated, active CHB patients. Baseline vitamin D levels are not associated with treatment outcomes, but were associated with normal ALT.
Abbreviations

    CHB, chronic hepatitis B; HBeAg, hepatitis B e antigen; TDF, tenofovir disoproxil fumarate; HBV, hepatitis B virus; 25[OH]D, 25-hydroxyvitamin D3; HCV, hepatitis C virus; ISG, interferon-stimulating gene; PegIFN, pegylated interferon-α 2a; ALT, alanine aminotransferase; AST, aspartate aminotransferase; TSH, thyroid-stimulating hormone; HBsAg, hepatitis B surface antigen; anti-HBs, hepatitis B surface antibody

Keywords

    Hepatitis B; Seasonal variation; Tenofovir disoproxil fumarate; Vitamin D deficiency

    Corresponding author. Address: Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, Shatin, New Territories, Hong Kong.

Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier Ireland Ltd. All rights reserved.

StephenW

研究论文
基线维生素D水平与慢性乙型肝炎临床指标和治疗结果的协会

    亨利沥-源CHAN1，Magdy Elkhashab2，伊Trinh3，赢得年轻Tak4，小莉MA5，万龙Chuang6，尹六月Kim7，爱德华B. Martins8，兰家Lin8，菲利普Dinh8，普里斯塔Charuworn8，格雷厄姆河Foster9，帕特里克Marcellin10

    香港中国大学1威尔斯亲王医院，香港
    2多伦多肝脏中心，多伦多，安大略省，加拿大
    3圣何塞消化内科，圣何塞，CA，USA
    4庆北国立大学医院，大邱，韩国
    医药，费城，宾夕法尼亚州，美国的5德雷克塞尔大学学院
    6高雄医学大学附设医院，高雄医学大学，台湾高雄
    7首尔国立大学医院，首尔，韩国
    8吉利德科学公司，福斯特市，CA，USA
    伦敦，伦敦，英国9大学玛丽皇后学院
    10 HOPITAL Beaujon，巴黎大学，法国巴黎

    2015年七月份送交27 2015年二月修订11 2015年6月，接受2015年6月22日可在线2


背景和目的

维生素D水平与慢性乙型肝炎（CHB）感染和治疗效果之间的关系不好阐明。我们测量治疗前血清维生素D（25-羟基维生素D3; 25 [OH] D3）的水平，并确定与在活性慢性乙型肝炎患者的临床参数和治疗结果的关联，而不晚期肝病参加一个全球临床试验。
方法

患者被随机分配到48周富马酸替诺福韦酯（TDF）加上聚乙二醇干扰素α-2a干扰素（PegIFN），TDF加上PegIFN 16周，然后TDF 32周，PegIFN 48周，或TDF为120周。单因素和多因素分析来确定维生素D，基本因素，而48周临床结果之间的关联。
结果

737名患者中，35％有不足（⩾20但<31纳克/毫升）和58％的缺陷（<20毫微克/毫升）的维生素D水平。在单因素分析，较低的维生素D水平显著具有以下基本参数有关：年龄小，降低尿酸水平，HBeAg阳性的状态，降低钙的水平，抽血在冬季或秋季和HBV基因型D.多变量分析显示，只有HBV基因型，抽血，钙离子浓度的季节和年龄保留了他们的关系。维生素D高的基线水平低HBV DNA，ALT正常，HBsAg与相关的48个独立的治疗组的一周，但联想，除ALT，成为在调整了年龄，性别，HBeAg和HBV基因型后无统计学意义。
结论

异常低维生素D水平之间的未经处理的，活跃的慢性乙肝患者非常普遍。基线维生素D水平不与治疗效果有关，但ALT正常有关联。
缩写

    慢性乙型肝炎，慢性乙型肝炎;大三阳，乙肝e抗原; TDF，富马酸替诺福韦酯;乙肝病毒，B型肝炎病毒; 25 [OH] D，25-羟基维生素D3;丙型肝炎病毒，丙型肝炎病毒; ISG，干扰素刺激的基因; PegIFN，聚乙二醇化α干扰素2a中; ALT，谷丙转氨酶; AST，天冬氨酸转氨酶; TSH，甲状腺刺激激素;的HBsAg，乙型肝炎表面抗原;抗-HBs，乙型肝炎表面抗体

关键词

    B型肝炎;季节变化;富马酸替诺福韦酯;维生素D缺乏症

    通讯作者。地址：内科及药物治疗，9系/威尔斯亲王医院，沙田，新界，香港F的王子。

版权所有©2015年欧洲协会为肝脏的研究。发布时间由Elsevier爱尔兰有限公司保留所有权利。

zgct

好文有意义

StephenW

Chan H L-Y, et al. J Hepatol. 2015;doi:10.1016/j.jhep.2015.06.025.
December 7, 2015

   
Levels of vitamin D among patients with chronic hepatitis B virus infection were extremely low and prevalent when the infection was left untreated. The low levels were, however, not associated with treatment outcomes.
See Also

   

“To our knowledge, this is the largest analysis of vitamin D levels among patients with [chronic HBV],” Henry Lik-Yuen Chan, MD, Prince of Wales Hospital, The Chinese University of Hong Kong, and colleagues wrote. “The analysis also comprises a board global sampling from 139 sites in Europe, Asia, North America, Australia and India.”

Henry Lik-Yuen Chan, MD

Henry Lik-Yuen Chan

The researchers randomly assigned 740 patients to either a dosage of tenofovir disoproxil fumarate (TDF) plus pegylated interferon alfa-2a  for 48 weeks, TDF plus PEG-IFN a-2a for 16 weeks followed by TDF for 32 weeks, PEG-IFN a-2a for 48 weeks, or TDF for 120 weeks.

The primary outcome was to determine associations between vitamin D, baseline factors, and week 48 clinical outcomes. Insufficient levels were deemed to be greater than 20 ng/mL and less than 31 ng/mL and deficient levels were considered to be less than 20 ng/mL.

Overall, 7% had normal vitamin D levels, 35% had insufficient and 58% had deficient levels out of 737 included patients.

In univariate analysis, lower vitamin D levels were associated with younger age, lower uric acid levels, a positive hepatitis B e antigen (HBeAg) status, lower calcium levels, blood drawn in winter or autumn and HBV genotype D. In multivariate analysis, HBV genotype, season of blood drawn, calcium level and age remained associated with lower vitamin D levels.

High baseline level of vitamin D was associated with low HBV DNA, normal alanine aminotransferase serum level and hepatitis B surface antigen positivity at 48 weeks. However, this association was no longer significant after adjusting for age, gender, HBeAg and HBV genotype, with the exception of ALT.

“Although the effect of vitamin D on virologic treatment outcomes were largely confounded by different clinical and virologic factors in this study, whether a low vitamin D level contributes to unsuccessful immune clearance and active hepatitis warrants further study,” the researchers concluded.

Disclosure: Chan reports advising and speaking for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Roche, MSD and Novartis; serving as a speaker for GlaxoSmithKline and Echosens; and receiving unrestricted grants for HBV research from Roche. Please see the full study for a list of all other authors’ relevant financial disclosures.

StephenW

陈H L-Y，等人。肝脏病学杂志。 2015年，DOI：10.1016 / j.jhep.2015.06.025。
2015年12月7日

   
的患者有慢性乙肝病毒感染者体内维生素D水平都非常低，普遍在感染不及时治疗。低水平，然而，不与治疗结果相关。
也可以看看

   

“据我们所知，这是维生素D水平患者的最大的分析[慢性HBV]，”亨利沥，陈源，医学博士，威尔斯亲王医院，香港中国大学，和同事写道。 “该分析还包括来自欧洲，亚洲，北美，澳大利亚和印度的139位点的板全球取样。”

亨利沥，陈源，MD

亨利沥，袁赞

研究人员随机分配740患者的富马酸替诺福韦酯（TDF）加聚乙二醇化干扰素α-2a或者48周，TDF加PEG-IFN一个-2a的16周，然后TDF 32周，PEG-IFN剂量的α-图2a为48周，或TDF为120周。

主要成果是确定维生素D，基本因素，而48周临床结果之间的关联。水平不足被认为是大于20毫微克/毫升，且小于31毫微克/毫升和水平不足被认为是小于20毫微克/毫升。

总体而言，7％有正常的维生素D水平，35％的人不足58％的水平不足出737包括患者。

在单因素分析，低维生素D水平与年龄小，降低尿酸水平，为乙型肝炎e抗原（HBeAg）状态，低血钙，血在冬季或秋季和HBV基因型D.在多变量分析，HBV得出相关基因型，血抽，钙水平和年龄赛季仍然以较低的维生素D水平相关联的。

维生素D高基线水平与低的HBV DNA，正常丙氨酸转氨酶血清水平和B型肝炎表面抗原阳性相关联的48周。不过，该协会已不再调整了年龄，性别，HBeAg和HBV基因型，除ALT后显著。

“尽管维生素D对病毒学治疗结果的影响在很大程度上混淆不同的临床和病毒学因素在这项研究中，无论是低维生素D水平有助于不成功免疫清除和活动性肝炎值得进一步研究，”研究人员得出结论。

披露：陈报告建议和发言艾伯维，施贵宝，Gilead Sciences公司，罗氏，MSD和诺华;作为一个扬声器，葛兰素史克和Echosens;和接收不受限制的补助金从罗氏乙肝病毒的研究。请参阅完整的研究对于所有其他作者的相关财务信息披露的名单。

tcl9456421

我前几天吃了20几天维生素d，每天400国际单位。前几天检查结果维生素d超标。所以吃维生素d之前必须先检查，后再吃