HBe 抗原陰性患者停用核苷（酸）類似物後，低抗 HBc 水平與

StephenW

HBe 抗原陰性患者停用核苷（酸）類似物後，低抗 HBc 水平與較低的病毒學復發風險相關
Valerie Ohlendorf 1 , Maximilian Wübbolding 1 2 3 , Paul Gineste 4 , Christoph Höner Zu Siederdissen 1 , Birgit Bremer 1 , Heiner Wedemeyer 1 3 , Markus Cornberg 1 2 3 , Benjamin Maasoumy 1 2 3
隸屬關係
隸屬關係

    1
    德國漢諾威漢諾威醫學院胃腸病學、肝病學和內分泌學系。
    2
    個體化感染醫學中心 (CiiM)，是德國漢諾威亥姆霍茲感染研究中心和漢諾威醫學院的合資企業。
    3
    德國感染研究中心 (DZIF)，合作夥伴網站 Hannover-Braunschweig，漢諾威，德國。
    4
    Abivax，法國巴黎。

    PMID：36152268 DOI：10.1111/liv.15433

抽象的

背景和目的：治療停止時血清抗 HBc 水平低與 HBeAg 陽性為主的隊列中較高的複發風險有關。我們調查了 HBeAg 陰性患者的抗 HBc 水平與復發的關係。

方法：在停止治療或接種疫苗之前，測定了 136 名 HBeAg 陰性患者的血清抗 HBc、HBsAg 和 HBcrAg 水平，這些患者參加了疫苗接種試驗（ABX-203，NCT02249988）。重要的是，疫苗接種對複發沒有影響。研究了生物標誌物與其複發預測值（HBV DNA >2,000 IU/ml ± ALT >2xULN）之間的相關性。

結果：治療停止後，50% (N=68) 的患者復發。與停止治療的反應者相比，治療停止前的中位抗 HBc 顯著更高（520 IU/ml 對 330 IU/ml，p=0.0098）。根據 Youden-Index，預測復發的最佳抗 HBc 截止值為 325 IU/ml。 35% 的抗 HBc 水平 <325 IU/ml 的患者與 60% 的 ≥325 IU/ml 的患者復發（p=0.0103；敏感性 50%，特異性 75%）。將 HBsAg (>3008 IU/ml) 或 HBcrAg (≥1790 U/ml) 與抗 HBc 的最佳臨界值相結合，復發患者的比例增加到 80% (p<0.0001) 和 74% (p=0.0006) ）， 分別。

結論：與主要為 HBeAg 陽性的隊列相比，在我們的 HBeAg 陰性患者隊列中，較低的抗 HBc 水平與核苷（酸）類似物停用後顯著降低的複發風險相關。絕大多數納入的患者是基因型 B 或 C，並且必須進一步評估對其他基因型的適用性。然而，作為宿主反應指標的抗 HBc 水平可能會被前瞻性地進一步探索用於預測模型。

關鍵詞：核苷（酸）類似物；慢性乙型肝炎；停止治療；病毒學復發。

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StephenW

Low anti-HBc levels are associated with lower risk of virological relapse after nucleos(t)ide analogue cessation in HBe antigen negative patients
Valerie Ohlendorf  1 , Maximilian Wübbolding  1   2   3 , Paul Gineste  4 , Christoph Höner Zu Siederdissen  1 , Birgit Bremer  1 , Heiner Wedemeyer  1   3 , Markus Cornberg  1   2   3 , Benjamin Maasoumy  1   2   3
Affiliations
Affiliations

    1
    Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School Hannover, Germany.
    2
    Centre for Individualized Infection Medicine (CiiM), a joint venture of Helmholtz Centre for Infection Research and Hannover Medical School, Hannover, Germany.
    3
    German Center for Infection Research (DZIF), Partner-Site Hannover-Braunschweig, Hannover, Germany.
    4
    Abivax, Paris, France.

    PMID: 36152268 DOI: 10.1111/liv.15433

Abstract

Background & aims: Low anti-HBc serum levels at time of therapy cessation were linked to a higher relapse-risk in predominantly HBeAg positive cohorts. We investigated the association of anti-HBc levels with relapse in HBeAg negative patients.

Methods: Serum levels of anti-HBc, HBsAg and HBcrAg were determined in 136 HBeAg negative patients, participating in a vaccination trial (ABX-203, NCT02249988), before treatment cessation or vaccination. Importantly, vaccination showed no impact on relapse. Correlation between the biomarkers and their predictive value for relapse (HBV DNA >2,000 IU/ml ± ALT >2xULN) was investigated.

Results: After therapy cessation 50% (N=68) of patients relapsed. Median anti-HBc prior to treatment stop was significantly higher among relapsers compared to off-treatment responders (520 IU/ml vs. 330 IU/ml, p=0.0098). The optimal anti-HBc cut-off to predict relapse was 325 IU/ml according to the Youden-Index. 35% of patients with anti-HBc level <325 IU/ml vs. 60% of those with values ≥325 IU/ml relapsed (p=0.0103; sensitivity 50%, specificity 75%). Combining the optimal cut-offs of HBsAg (>3008 IU/ml) or HBcrAg (≥1790 U/ml) with anti-HBc increased the proportion of patients with relapse to 80% (p<0.0001) and 74% (p=0.0006), respectively.

Conclusion: In contrast to predominantly HBeAg positive cohorts, in our cohort of HBeAg negative patients lower anti-HBc levels are associated with a significantly lower relapse-risk after nucleos(t)ide analog cessation. The vast majority of included patients were either genotype B or C and the applicability to other genotypes has to be further evaluated. However, anti-HBc level as an indicator of the host response might be prospectively further explored for prediction models.

Keywords: Nucleos(t)ide analogue; chronic hepatitis B; treatment cessation; virological relapse.

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