Relationship between precore / core promoter mutants, HBeAg levels and serologic

StephenW

Relationship between precore / core promoter mutants, HBeAg levels and serological response in HBeAg-positive chronic hepatitis B treated with nucleos(t)ide analogues


      EASL 2012

Speaker: Roeland Zoutendijk Author: R. Zoutendijk1*, M. Sonneveld2, J. Reijnders2, A. van Vuuren2, S. Pas1, B. Hansen1, A. Boonstra2, H. Janssen2 Affiliation: 1Erasmus MC, 2Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. *[email protected]

Background: Precore (PC) and core promoter (BCP) mutations are the most prevalent naturally occurring variations of hepatitis B virus (HBV) and are thought to reduce the production of HBeAg. Moreover, patients with these mutations remain viraemic despite HBeAg seroconversion and are at risk for developing liver related complications.

Methods: We investigated the influence PC/BCP mutants and their relation with HBeAg levels and HBeAg seroconversion in 138 HBeAg-positive patients treated with different nucleos(t)ide analogues. The presence of mutants was assessed at baseline by line probe assay (Innogenetics, Ghent, Belgium), HBeAg levels were measured by Elecsys (Roche). Median duration of therapy was 29 (IQR 18-56) months.

Results: Patients were predominantly male (78%) and harbored genotypes A (33%), B (18%), C (16%), D (27%) or other (5%). Patients were treated with lamivudine (LAM, 38%), adefovir (ADV, 22%), entecavir (30%), tenofovir (TDF, 6%) and TDF/ADV-LAM (4%). Fifty-three (38%) patients had wildtype (WT) virus at baseline, 25 (18%) PC, 33 (24%) BCP and 27 (20%) had both PC and BCP mutants. Baseline HBeAg levels were different within these 4 groups: 2.68 (WT), 1.77 (PC), 1.81 (BCP) and 1.48 (both mutants) log U/mL respectively (p< 0.001) and HBeAg levels correlated with HBV DNA (r=0.55; p< 0.001). HBeAg-seroconversion was achieved in 45 (33%) patients and HBsAg-seroconversion in 6 (4%) patients. In multivariate analysis, the presence of PC and/or BCP mutants (HR 2.30, p= 0.045), baseline HBV DNA (HR 0.82, p=0.08) and ALT (HR 1.04, p=0.02), but not HBeAg levels (p=0.36) were independently associated with HBeAg seroconversion. Patients with PC mutants had a much lower probability of achieving HBV DNA < 2000 IU despite HBeAg-seroconversion compared to patients without PC mutants (68% versus 100%, p=0.003). Confirmed HBeAg relapse was more frequently noted in patients with BCP mutations (46% versus 19%, p=0.06).

Conclusions: Presence of PC/BCP mutants before NUC therapy was associated with lower levels of HBeAg and a higher probability of HBeAg seroconversion. However, presence of PC/BCP mutants also predisposed to persistent replication or HBeAg relapse after HBeAg seroconversion.

StephenW

前C区/核心启动子突变，HBeAg的水平和血清学反应在核苷（酸）IDE类似物治疗HBeAg阳性慢性肝炎乙之间的关系


  欧洲肝病学会2012

主讲人：Roeland Zoutendijk作者：R. Zoutendijk1 *，A.面包车Vuuren2 M. Sonneveld2，J. Reijnders2，S. Pas1，B. Hansen1，A. Boonstra2，H. Janssen2尔：1Erasmus MC大学医学中心，2Erasmus MC鹿特丹，荷兰鹿特丹。 * r.zoutendijk @ erasmusmc.nl

背景：前C（PC）和核心启动子（BCP）突变是自然发生的最流行的B型肝炎病毒（HBV）的变化，被认为是减少生产的HBeAg。此外，这些突变的患者仍然在病毒感染期，尽管HBeAg血清转换和发展肝脏相关并发症的风险。

方法：我们研究了PC /BCP突变的影响及其与HBeAg水平在138个不同的核苷（酸）IDE类似物治疗的HBeAg阳性患者和HBeAg转阴的关系。评估基准线探针法（Innogenetics公司，比利时根特）突变体的存在，HBeAg的水平测量Elecsys（罗氏）。治疗时间中位数为29个月（IQR 18-56）。

结果：患者以男性为主（78％）和窝藏基因型（33％），乙（18％），C（16％），D类（27％）或其他（5％）。患者用拉米夫定，阿德福韦（ADV，22％）（林，38％），恩替卡韦（30％），替诺福韦（TDF的6％）和TDF / ADV林（4％）。五十三（38％）患者在基线野生型（WT）的病毒，电脑，33（24％），BCP和27（20％）25（18％），PC和BCP突变。基线HBeAg的水平分别为这4组内不同：2.68（野生），1.77（PC）的，口岸（1.81）和1.48（包括突变）分别日志U / ml的（P <0.001）和相关的HBeAg的水平与HBV DNA（R = 0.55; P <0.001）。取得了45例（33％）和6（4％）患者的HBsAg转阴，e抗原转阴。在多变量分析，在场的PC和/或BCP突变（人力资源2.30，P = 0.045），基线HBV DNA（人力资源0.82，P = 0.08）和ALT（HR 1.04，P = 0.02），但不HBeAg的水平（P = 0.36）的独立与HBeAg血清转换。与PC突变患者的HBeAg血清转换的实现HBV  -  DNA <2000 IU的概率要低得多，尽管相比无PC突变的患者（68％和100％，P = 0.003）。证实HBeAg的复发更频繁地注意到，在患者的BCP突变（46％比19％，P = 0.06）。

结论：治疗前国统会的PC / BCP突变的存在是与HBeAg的水平较低和较高的HBeAg血清转换的概率。然而，也倾向于持续复制或e抗原HBeAg血清转换后复发的PC / BCP突变的存在。

StephenW

Relationship between Precore / Core Promoter Mutants, HBeAg levels and Serological Response in HBeAg-Positive Chronic Hepatitis B Patients treated with Nucleos(t)ide Analogues 2
	Reported by Jules Levin EASL 2012 Roeland Zoutendijk, Milan J. Sonneveld, Jurrien Reijnders, Anneke J. Van Vuuren,Bettina E. Hansen, Andre Boonstra and Harry L.A. JanssenDepartment of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands   EASL: Relationship between precore / core promoter mutants, HBeAg levels and serological response in HBeAg-positive chronic hepatitis B treated with nucleos(t)ide analogues - (05/07/12)Conclusions: Presence of PC/BCP mutants before NUC therapy was associated with lower levels of HBeAg and a higher probability of HBeAg seroconversion. However, presence of PC/BCP mutants also predisposed to persistent replication or HBeAg relapse after HBeAg seroconversion.        EASL: Presence of precore and core promoter mutants limits the probability of response to peginterferon in hepatitis B e antigen-positive chronic hepatitis B - (05/07/12)