先前曾接触过乙型肝炎病毒的患者在接受糖皮质激素治疗后

StephenW

Risk of hepatitis B surface antigen seroreversion after corticosteroid treatment in patients with previous hepatitis B virus exposure [url=]Grace Lai-Hung Wong[/url]1,2,3
,  [url=]Vincent Wai-Sun Wong[/url]1,2,3
,  [url=]Becky Wing-Yan Yuen[/url]1,2
,  [url=]Yee-Kit Tse[/url]1,2
,  [url=]Terry Cheuk-Fung Yip[/url]1,2
,  [url=]Hester Wing-Sum Luk[/url]2
,  [url=]Grace Chung-Yan Lui[/url]2
,  [url=]Henry Lik-Yuen Chan[/url]1,2,3,,[url=]Correspondence information about the author  Henry Lik-Yuen Chan[/url]Email the author  Henry Lik-Yuen Chan





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DOI: https://doi.org/10.1016/j.jhep.2019.08.023 |

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Highlights

• •HBsAg− patients (anti-HBc+ but anti-HBs−) are at increased risk of HBsAg seroreversion after corticosteroid therapy.
• •The peak daily dose of corticosteroid is a more important risk factor for hepatitis flares than treatment duration.
• •In contrast, dose and duration of corticosteroid use are not associated with the risk of HBsAg reversion.
  

Background & AimsSystemic corticosteroids may cause HBV reactivation, but the impact on patients with previous HBV exposure is poorly defined. We aimed to study the risk of HBsAg seroreversion and hepatitis flare in patients with previous HBV exposure.


MethodsPatients who were negative for HBsAg and received corticosteroids between 2001–2010 were included. Patients who were positive for antibody to HBsAg (anti-HBs) and/or to HBcAg (anti-HBc) were defined as having previous HBV exposure. The primary endpoint was HBsAg seroreversion; the secondary endpoint was hepatitis flare (alanine aminotransferase >80 U/L) at 1 year.


ResultsA total of 12,997 patients fulfilled the inclusion criteria: anti-HBs positive only (n = 10,561); anti-HBc positive only (n = 970); anti-HBs & anti-HBc positive (n = 830) and anti-HBs & anti-HBc negative (n = 636). HBsAg seroreversion occurred in 165 patients. Patients who were anti-HBc positive only had a higher risk of HBsAg seroreversion (1-year incidence 1.8%) than those negative for both anti-HBs & anti-HBc (0%; p = 0.014). Patients with previous HBV exposure had a similarly low risk of liver failure as unexposed individuals (1.1% vs. 0.9%). The risk of a hepatitis flare started to increase in those receiving corticosteroids at peak daily doses of 20–40 mg (adjusted hazard ratio [HR] 2.19, p = 0.048) or >40 mg (aHR 2.11, p = 0.015) prednisolone equivalents for <7 days, and was increased at treatment durations of 7–28 days and >28 days (aHR 2.02–3.85; p <0.001–0.012).


ConclusionsIn HBsAg-negative patients who were only anti-HBc positive, high peak daily doses of corticosteroids increased the risk of hepatitis flare, but not seroreversion. The rate of liver failure was low and similar in HBV exposed and unexposed individuals; there were no deaths, nor any requirement for liver transplantation.


Lay summaryIt is important to know the hepatitis B virus (HBV) status before starting corticosteroid therapy. Patients with resolved HBV infection without detectable immunity are at an increased risk of HBV surface antigen seroreversion after corticosteroid therapy. High peak daily doses of corticosteroids (>40 mg prednisolone equivalents) increase the risk of hepatitis flare, but not seroreversion, in patients with previous exposure to HBV, irrespective of the duration of treatment. Interval monitoring of liver biochemistries is essential for the early detection of hepatitis flares in these patients.



Keywords:                [url=https://www.journal-of-hepatology.eu/action/doSearch?searchType=quick&occurrences=all<rlSrch=true&searchScope=fullSite&searchText=Antiviral treatment&code=jhepat-site]Antiviral treatment[/url], [url=https://www.journal-of-hepatology.eu/action/doSearch?searchType=quick&occurrences=all<rlSrch=true&searchScope=fullSite&searchText=Icteric flare&code=jhepat-site]Icteric flare[/url], Immunosuppressants, Corticosteroid, HBV, [url=https://www.journal-of-hepatology.eu/action/doSearch?searchType=quick&occurrences=all<rlSrch=true&searchScope=fullSite&searchText=Occult hepatitis&code=jhepat-site]Occult hepatitis[/url]

StephenW

先前曾接触过乙型肝炎病毒的患者在接受糖皮质激素治疗后发生乙型肝炎表面抗原血清逆转的风险
黄丽红1,2,3
，Vincent Wai-Sun Wong1,2,3
，袁咏仪1,2
，Yee-Kit Tse1,2
，叶卓丰叶1,2
，Hester Wing-Sum Luk2
吕中恩2
，Henry Lik-Yuen Chan1,2,3，low asterisk，'有关作者Henry Lik-Yuen Chan的通讯信息通过电子邮件发送给作者Henry Lik-Yuen Chan
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DOI：https：//doi.org/10.1016/j.jhep.2019.08.023 |
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强调

    •皮质类固醇治疗后，HBsAg−患者（抗-HBc +但抗-HBs-）的HBsAg血清逆转的风险增加。
    •每日最高剂量的皮质类固醇激素是导致肝炎发作的重要危险因素，而不是治疗持续时间。
    •相反，使用皮质类固醇的剂量和持续时间与HBsAg逆转的风险无关。

背景与目标

全身性皮质类固醇可能引起HBV重新激活，但对先前接触过HBV的患者的影响尚不清楚。我们旨在研究先前接触过HBV的患者发生HBsAg逆转和肝炎发作的风险。
方法

纳入2001-2010年间HBsAg阴性并接受糖皮质激素治疗的患者。对HBsAg（抗HBs）和/或HBcAg（抗HBc）抗体呈阳性的患者被定义为以前曾接触过HBV。主要终点为HBsAg血清逆转；次要终点是在1年出现肝炎发作（丙氨酸转氨酶> 80 U / L）。
结果

共有12997名患者符合纳入标准：仅抗HBs阳性（n = 10,561）；仅抗HBc阳性（n = 970）；抗HBs和抗HBc阳性（n = 830）和抗HBs和抗HBc阴性（n = 636）。 165例患者发生了HBsAg血清逆转。抗HBc阳性的患者仅发生HBsAg血清逆转的风险较高（1年发生率1.8％），而抗HBs和抗HBc阴性的患者（0％； p = 0.014）。先前曾接触过HBV的患者与未接触过的个体相比，肝衰竭的风险也较低（1.1％比0.9％）。每日泼尼松龙当量剂量为20–40μmg（调整后的危险比[HR] 2.19，p = 0.048）或>40μmg（aHR 2.11，p = 0.015）时，接受皮质类固醇激素治疗的人开始出现肝炎发作的风险开始增加。 <7天，并在7–28天和> 28天的治疗时间增加（aHR 2.02–3.85； p <0.001–0.012）。
结论

在仅抗HBc阳性的HBsAg阴性患者中，每天高剂量的皮质类固醇高剂量会增加发生肝炎发作的风险，而不会导致血清逆转。 HBV暴露者和未暴露者的肝衰竭率低且相似。没有死亡，也没有肝移植的要求。
放置摘要

在开始糖皮质激素治疗之前，了解乙型肝炎病毒（HBV）的状态非常重要。皮质类固醇治疗后，解决了HBV感染但无可检测的免疫力的患者，发生HBV表面抗原血清逆转的风险增加。每天服用高剂量的皮质类固醇（> 40 mg泼尼松龙当量）会增加先前接触过HBV的患者发生肝炎的风险，而不会引起血清逆转，而与治疗时间无关。肝生物化学的定期监测对于早期发现这些患者的肝炎发作至关重要。
关键字：
抗病毒治疗，黄疸，免疫抑制剂，糖皮质激素，HBV，隐匿性肝炎