表面抗原水平帮助分类干扰素治疗期间ALT爆发

StephenW

Close Monitoring of Hepatitis B Surface Antigen Levels Helps Classify Flares During Peginterferon Therapy and Predicts Treatment Response

    Milan J. Sonneveld1,
    Roeland Zoutendijk1,
    Hajo J. Flink1,
    Louwerens Zwang2,
    Bettina E. Hansen1,3, and
    Harry L. A. Janssen1

+ Author Affiliations

    1Department of Gastroenterology and Hepatology
    2Department of Clinical Chemistry
    3Department of Biostatistics, Erasmus MC University Medical Center, Rotterdam, The Netherlands

    Correspondence: Harry L. A. Janssen, MD, PhD, Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, 's Gravendijkwal 230, Rm Ha 204, 3015 CE Rotterdam, The Netherlands ([email protected]).

Abstract

Background. Alanine aminotransferase (ALT) flares occur frequently during peginterferon (PEG-IFN) therapy. We related occurrence of flares to presence of precore (PC) and/or basal core promoter (BCP) mutants and studied kinetics of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) levels during flares.

Methods. Fifty of 214 (23%) patients treated with PEG-IFN ± lamivudine for 52 weeks experienced flares. Flares were host-induced (ALT elevation followed by HBV DNA decline, n = 19), virus-induced (HBV DNA increase with subsequent ALT elevation, n = 17) or indeterminate (n = 14). Presence of wild-type (WT) or non-WT (detectable PC/BCP mutants) was studied by lineprobe assay.

Results. Fifty-eight percent of host-induced flares occurred in WT HBV patients, whereas 94% of virus-induced flares occurred in patients with PC and/or BCP mutants (P = .003). HBsAg loss was only achieved in patients with a host-induced flare, and WT patients with a host-induced flare cleared HBsAg in 64% of cases. Serum HBsAg levels declined after a host-induced flare, whereas virus-induced flares were accompanied by stable or increasing levels of HBsAg. Patients with a host-induced flare achieved a mean HBsAg reduction of 3.24 log IU/mL, compared with 0.25 log IU/mL in virus-induced flares (P < .001). Patients who achieved a decline in HBsAg of >0.5 log IU/mL within 4 weeks after the flare cleared HBsAg in 64% (7 of 11) of cases.

Conclusions. Host-induced flares are associated with WT virus and may result in decline and clearance of HBV DNA, HBeAg, and HBsAg. Monitoring of HBsAg levels during and after flares may help predict a favorable treatment outcome.

StephenW

米兰研究Sonneveld1，
    罗兰Zoutendijk1，
    哈乔J. Flink1，
    Louwerens Zwang2，
    贝蒂娜E. Hansen1，3，和
    哈利·L. A. Janssen1

+作者背景

    1胃肠病学和肝病学杂志
    2临床化学
    3生物统计学，Erasmus MC大学医学中心，鹿特丹，荷兰

    通讯：：哈里·LA扬森，医学博士，哲学博士，胃肠病学和肝病学系，Erasmus医学中心，鹿特丹大学医学中心，旗下的Gravendijkwal 230，厦204室，3015 CE鹿特丹，荷兰（h.janssen @ erasmusmc.nl）。

抽象

背景。聚乙二醇干扰素（PEG-IFN）治疗过程中经常出现谷丙转氨酶（ALT）爆发。相关的爆发发生前C区（PC）的存在和/或基本核心启动子（BCP）突变体，并研究了在爆发动力学的B型肝炎e抗原（HBeAg）和乙型肝炎表面抗原（HBsAg）水平。

方法。五，共214例（23％）与PEG-IFN±拉米夫定治疗52周的有经验的爆发。爆发主机引起的（ALT升高，HBV DNA下降，N = 19），病毒引起的（HBV DNA，随后ALT升高的增加，N = 17）或不确定（N = 14）。野生型（WT）或检测到非-WT（PC / BCP突变体）的存在下，研究了由线路探查测定。

结果。百分之八的主机引起的爆发发生在WT乙肝患者，而94％的病毒引起的爆发发生在患者与PC和/或BCP变异（P = 0.003）。患者与主机引起的爆发，只实现了HBsAg消失和主机引起的爆发WT患者HBsAg清除64％的情况下。血清HBsAg水平下降主机引起的爆发后，而病毒引起的爆发伴随着稳定或增加的HBsAg水平。主机引起的爆发的患者取得了平均0.25logIU / mL的病毒引起的爆发（P <0.001）相比，减少3.24logIU / mL的乙肝表面抗原。谁取得了下降> 0.5logIU / mL的4个星期内爆发后的乙肝表面抗原HBsAg清除的情况下，64％（11）的患者。