HBeAg 阴性慢性乙型肝炎患者在 peg-干扰素加核苷酸类似物治疗

StephenW

HBeAg 阴性慢性乙型肝炎患者在 peg-干扰素加核苷酸类似物治疗或不治疗后的前瞻性五年随访
罗宾 Erken 1、弗拉基米尔 V Loukachov 2、Annikki de Niet 3、Louis Jansen 3、Femke Stelma 3、Jeltje T Helder 3、Martine W Peters 3、Hans L Zaaijer 4、Neeltje A Kootstra 5、Sophie B Willemse 1、Hendrik W Reesink 1
隶属关系
隶属关系

    1
    阿姆斯特丹 UMC，阿姆斯特丹大学，胃肠病学和肝病学系，阿姆斯特丹胃肠病学内分泌代谢，Meibergdreef 9，阿姆斯特丹，荷兰。
    2
    实验免疫学系，阿姆斯特丹 UMC，位置 AMC，Meibergdreef 9, 1105AZ，阿姆斯特丹，荷兰。
    3
    阿姆斯特丹 UMC 胃肠病学和肝病学系，位置 AMC，Meibergdreef 9, 1105AZ，阿姆斯特丹，荷兰。
    4
    Sanquin 血液供应基金会，Plesmanlaan 125，阿姆斯特丹，荷兰。
    5
    实验免疫学系，阿姆斯特丹 UMC，阿姆斯特丹感染与免疫研究所，阿姆斯特丹大学，阿姆斯特丹，荷兰。

    PMID：35677522 PMCID：PMC9168707（2023-05-01 可用） DOI：10.1016/j.jceh.2021.12.011

抽象的

背景：对于病毒载量低的 HBeAg 阴性患者，不推荐目前可用的慢性乙型肝炎 (CHB) 治疗方案。然而，这些患者可能会通过实现功能性治愈而受益于治疗，该功能性治愈定义为 HBsAg 消失和无法检测到的 HBV DNA。本研究评估了在这些患者中与未治疗相比，peg-干扰素-α-2a (peg-IFN) 和阿德福韦或替诺福韦联合治疗的长期效果。

方法： HBV-DNA 水平 < 20,000 IU/mL (n = 151) 的 HBeAg 阴性 CHB 患者先前按 1:1:1 随机分配接受 peg-IFN 180 μg/周加阿德福韦 10 mg/天或替诺福韦 245 mg/天，或不治疗，并在一项开放标签研究中治疗 48 周。在这项前瞻性长期随访研究中，每年对患者进行监测，直至治疗结束后五年（第 308 周）。主要结果是持续的 HBsAg 消失，次要结果是 HBsAg 和 HBV-DNA 水平随时间的动态变化。

结果：在 131 名随访患者中，经过 5 年的随访，118 名患者的 HBsAg 状态已知。所有组的 HBsAg 下降相似 (P = 0.703)：8/43 (18.6%) peg-IFN + 阿德福韦，4/34 (11.7%) peg-IFN + 替诺福韦和 6/41 (14.6%)未经治疗的患者。 HBsAg 消失时间在各组之间没有差异（P = 0.641）。低基线 HBsAg 水平和基因型 A 与 HBsAg 丢失独立相关，与分配无关。在所有患者组的随访期间，HBsAg 和 HBV-DNA 水平下降相似。

结论：这项前瞻性随机对照研究表明，HBsAg 消失超时不受核苷酸类似物和 Peg-IFN 联合治疗的影响。无论治疗分配如何，低基线 HBsAg 水平都可以预测 HBsAg 消失。

关键词：ADV，阿德福韦酯； ALT，丙氨酸氨基转移酶； CHB，慢性乙型肝炎； EOT，治疗结束； GZ，灰色地带； HBeAg，乙型肝炎 e 抗原； HBsAg，乙型肝炎表面抗原； HCC，肝细胞癌； HNCH、HBeAg 阴性慢性感染； NA，核苷类似物； ROC，接收器操作特性； TAF，替诺福韦艾拉酚胺富马酸盐； TDF，富马酸替诺福韦酯； ULN，正常上限； UMC，大学医学中心；联合治疗；功能性治愈；乙型肝炎病毒;非活动载体；低病毒载量；聚乙二醇干扰素，聚乙二醇干扰素。

© 2022 印度全国肝脏研究协会。

StephenW

A Prospective Five-Year Follow-up After peg-Interferon Plus Nucleotide Analogue Treatment or no Treatment in HBeAg Negative Chronic Hepatitis B Patients
Robin Erken 1 , Vladimir V Loukachov 2 , Annikki de Niet 3 , Louis Jansen 3 , Femke Stelma 3 , Jeltje T Helder 3 , Martine W Peters 3 , Hans L Zaaijer 4 , Neeltje A Kootstra 5 , Sophie B Willemse 1 , Hendrik W Reesink 1
Affiliations
Affiliations

    1
    Amsterdam UMC, University of Amsterdam, Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Meibergdreef 9, Amsterdam, the Netherlands.
    2
    Department of Experimental Immunology, Amsterdam UMC, Location AMC, Meibergdreef 9, 1105AZ, Amsterdam, the Netherlands.
    3
    Department of Gastroenterology and Hepatology, Amsterdam UMC, Location AMC, Meibergdreef 9, 1105AZ, Amsterdam, the Netherlands.
    4
    Sanquin Blood Supply Foundation, Plesmanlaan 125, Amsterdam, the Netherlands.
    5
    Department of Experimental Immunology, Amsterdam UMC, Amsterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, the Netherlands.

    PMID: 35677522 PMCID: PMC9168707 (available on 2023-05-01) DOI: 10.1016/j.jceh.2021.12.011

Abstract

Background: Currently available treatment options for chronic hepatitis B (CHB) are not recommended for HBeAg-negative patients with a low viral load. These patients may however benefit from treatment by achieving a functional cure, defined by HBsAg-loss and undetectable HBV DNA. This study evaluated the long-term effect of combination treatment with peg-interferon-alpha-2a (peg-IFN) and adefovir or tenofovir compared to no treatment in these patients.

Methods: HBeAg-negative CHB patients with HBV-DNA levels < 20,000 IU/mL (n = 151) were previously randomised 1:1:1 for peg-IFN 180 μg/week plus either adefovir 10 mg/day or tenofovir 245 mg/ day, or no treatment and treated for 48 weeks in an open-label study. In this prospective long-term follow-up study, patients were monitored yearly up to five years after end of treatment (week 308). The primary outcome was sustained HBsAg-loss and secondary outcome the dynamics of HBsAg and HBV-DNA levels over time.

Results: Of the 131 followed patients, the HBsAg-status was known for 118 patients after five-year follow-up. HBsAg-loss occurred similarly (P = 0.703) in all arms: 8/43 (18.6%) peg-IFN + adefovir, 4/34 (11.7%) peg-IFN + tenofovir, and 6/41 (14.6%) among the untreated patients. The time to HBsAg-loss did not differ between groups (P = 0.641). Low baseline HBsAg levels and genotype A were independently associated with HBsAg-loss irrespective of allocation. HBsAg and HBV-DNA levels declined similarly during follow-up in all patient groups.

Conclusions: This prospective randomised controlled study showed that HBsAg-loss overtime was not influenced by treatment with a combination of nucleotide analogue and Peg-IFN. Low baseline HBsAg levels can predict HBsAg-loss irrespective of treatment allocation.

Keywords: ADV, Adefovir dipivoxil; ALT, Alanine aminotransferase; CHB, Chronic hepatitis B; EOT, End of treatment; GZ, Grey zone; HBeAg, Hepatitis B e antigen; HBsAg, Hepatitis B surface antigen; HCC, Hepatocellular Carcinoma; HNCH, HBeAg-negative chronic infection; NA, Nucleot(s)ide analogue; ROC, Receiver operating characteristic; TAF, Tenofovir alafenamide fumarateor; TDF, Tenofovir disoproxil fumarate; ULN, Upper limit of normal; UMC, University Medical Centers; combination therapy; functional cure; hepatitis B virus; inactive carrier; low viral load; peg-IFN, Pegylated-interferon.

© 2022 Indian National Association for Study of the Liver.

StephenW

http://www.jcehepatology.com/article/S0973688321005971/pdf