停用有效抗病毒治疗的非肝硬化 HBeAg 阴性慢性乙型肝炎患者

StephenW

停用有效抗病毒治疗的非肝硬化 HBeAg 阴性慢性乙型肝炎患者血清 HBV RNA 的意义
Margarita Papatheodoridi #1 2、Eleni Papachristou #3、Zissis Moschidis #3、Emilia Hadziyannis 4、Eirini Rigopoulou 5、Kalliopi Zachou 5、François Villeret 6、Gkikas Magiorkinis 3、Aggeliki Lyberopoulou 5、Nikolaos Gatselis 5、Ioannis V 1、乔治·N·达莱科斯 5、法比安·祖林 6、迪米特里奥斯·帕拉斯凯维斯 3、乔治·V·帕帕西奥多里迪斯 1
隶属关系
隶属关系

    1
    希腊雅典莱科综合医院国立和 Kapodistrian 大学医学院胃肠病学系。
    2
    伦敦大学学院，肝脏和消化健康研究所，皇家自由校区，伦敦，英国。
    3
    希腊雅典国立和 Kapodistrian 大学医学院卫生和流行病学系。
    4
    第二内科，雅典国立和卡波迪斯蒂安大学健康科学学院，雅典总医院“Hippokratio”，雅典，希腊。
    5
    希腊拉里萨色萨利大学医学院医学系和内科研究实验室。
    6
    INSERM U1052 - 里昂癌症研究中心 (CRCL)，69008，里昂，法国。

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同等贡献。

    PMID：35789515 DOI：10.1111/jvh.13729

抽象的

在停用核苷（酸）类似物（NAs）的患者中，HBV RNA 被认为是一个有希望的预测因子。我们确定了停用 NA 的非肝硬化 HBeAg 阴性患者的 HBV RNA 水平，并评估了他们对 12 个月结果的可预测性。包括 57 名 DARING-B 研究的患者。在治疗结束 (EOT) 后 0-3 个月抽取的每月储存的血清样本中测定 HBV RNA 水平。还评估了先前在同一队列中确定的其他标志物，包括乙型肝炎核心相关抗原 (HBcrAg)。 7% 的患者在 EOT 时可检测到 HBV RNA，这些患者出现病毒学/临床复发并在第 2 个月需要再次治疗；在EOT HBV RNA检测不到的患者中，12个月病毒学复发、临床复发和再治疗的累积率分别为68%、28%和21%（P≤0.008）。 19% 的患者在 EOT 后第 1 个月可检测到 HBV RNA，这与较高的病毒学复发概率有关（P=0.001）。 HBV RNA 水平与 HBV DNA、HBcrAg、ALT 和干扰素诱导的蛋白 10 显着相关，但与 HBsAg 水平无关。联合 EOT HBV RNA 和 HBcrAg 检测和/或 HBsAg >1000 IU/mL 仅与更高的再治疗概率相关，具有比单独的 HBV RNA 更高的敏感性和更低的特异性。总之，少数非肝硬化 HBeAg 阴性患者在长期有效的 NAs 治疗下可检测到血清 HBV RNA，由于停用 NA 后严重的临床复发，早期再治疗敏感性低但特异性为 100%。 EOT HBV RNA 与 HBcrAg 和/或高 HBsAg 水平的组合提高了预测 NAs 撤除后再治疗的敏感性但降低了特异性。

关键词：HBV RNA；停产；乙型肝炎；乙型肝炎核心相关抗原；复发;再治疗。

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StephenW

Significance of serum HBV RNA in non-cirrhotic HBeAg-negative chronic hepatitis B patients who discontinue effective antiviral therapy
Margarita Papatheodoridi #  1   2 , Eleni Papachristou #  3 , Zissis Moschidis #  3 , Emilia Hadziyannis  4 , Eirini Rigopoulou  5 , Kalliopi Zachou  5 , François Villeret  6 , Gkikas Magiorkinis  3 , Aggeliki Lyberopoulou  5 , Nikolaos Gatselis  5 , Ioannis Vlachogiannakos  1 , Spilios Manolakopoulos  1 , George N Dalekos  5 , Fabien Zoulim  6 , Dimitrios Paraskevis  3 , George V Papatheodoridis  1
Affiliations
Affiliations

    1
    Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
    2
    University College of London, Institute of Liver and Digestive Health, Royal Free Campus, London, UK.
    3
    Department of Hygiene and Epidemiology, Medical School of National and Kapodistrian University of Athens, Greece.
    4
    2nd Department of Internal Medicine, National and Kapodistrian University of Athens School of Health Sciences, General Hospital of Athens "Hippokratio", Athens, Greece.
    5
    Department of Medicine and Research Laboratory of Internal Medicine, Thessaly University Medical School, Larissa, Greece.
    6
    INSERM U1052 - Cancer Research Center of Lyon (CRCL), 69008, Lyon, France.

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Contributed equally.

    PMID: 35789515 DOI: 10.1111/jvh.13729

Abstract

HBV RNA is considered as a promising predictor in patients who discontinue nucleos(t)ide analogues (NAs). We determined HBV RNA levels in non-cirrhotic HBeAg-negative patients who discontinued NAs and assessed their predictability for 12-month outcomes. Fifty-seven patients of DARING-B study were included. HBV RNA levels were determined in stored monthly serum samples drawn at 0-3 months after end of therapy (EOT). Other markers previously determined in the same cohort including hepatitis B core related antigen (HBcrAg) were also assessed. HBV RNA at EOT was detectable in 7% of patients, who developed virological/clinical relapse and required retreatment at month 2; in patients with undetectable EOT HBV RNA, 12-month cumulative rates of virological relapse, clinical relapse and retreatment were 68%, 28% and 21%, respectively (P≤0.008). HBV RNA at month-1 after EOT was detectable in 19% of patients being associated with higher probability only of virological relapse (P=0.001). HBV RNA levels correlated significantly to HBV DNA, HBcrAg, ALT and interferon-induced protein-10, but not HBsAg levels. Combined EOT HBV RNA and HBcrAg detection and/or HBsAg >1000 IU/mL was associated only with higher probability of retreatment having higher sensitivity and lower specificity than HBV RNA alone. In conclusion, serum HBV RNA is detectable in a minority of non-cirrhotic HBeAg-negative patients under effective long-term NAs therapy offering low sensitivity but 100% specificity for early retreatment due to severe clinical relapses after NA discontinuation. The combinations of EOT HBV RNA with HBcrAg and/or high HBsAg levels increase sensitivity but decrease specificity for prediction of retreatment after NAs withdrawal.

Keywords: HBV RNA; discontinuation; hepatitis B; hepatitis B core related antigen; relapse; retreatment.

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