慢性乙型肝炎患者的核苷（酸）类似物戒断

StephenW

慢性乙型肝炎患者的核苷（酸）类似物戒断


慢性乙型肝炎（CHB）患者停止核苷（酸）类似物（NA）治疗后的停药结果取决于停药时的乙型肝炎表面抗原（HBsAg）水平和患者种族。发表在胃肠病学上的一项研究结果。

纳入了 1500 多名 HBsAg 阳性、乙型肝炎 e 抗原 (HBeAg) 阴性且在停用 NA 时病毒受到抑制的 CHB 患者。这项国际多中心队列研究排除了肝细胞癌患者、丙型肝炎和/或 HIV 等合并感染患者，以及在过去 12 个月内接受过聚乙二醇 (PEG-) 干扰素治疗的患者。

主要结果是 HBsAg 消失，被认为是慢性乙型肝炎的功能性治愈。次要结局包括病毒学复发，定义为至少 2000 IU/mL 的乙型肝炎 DNA 单次升高、再治疗和肝脏相关问题，如肝脏失代偿。

总共有 1552 名患者被纳入研究。停止治疗的平均年龄为 52.9±11.3 岁，72.3% 为男性，86.7% 为亚洲人，11.3% 为白人。大多数患者在停止治疗前接受恩替卡韦（63.2%）或富马酸替诺福韦二吡呋酯（27.1%）治疗。

与亚洲患者相比，白人患者的 HBsAg 消失累积概率显着更高（36.5% vs 10.9%；P <.001）。 HBsAg <100 IU/mL 的患者具有最有利的结果，与种族无关。然而，与亚洲患者相比，在 NA 退出时获得 30% 累积 HBsAg 消失概率所需的 HBsAg 阈值要高得多，分别为 <1000 IU/mL 和 <100 IU/mL。

到 48 个月时，超过 80% 的患者出现病毒学复发，超过一半的患者需要再治疗。肝脏失代偿很少见，仅发生在 19/1552 名患者中，尽管失代偿的死亡率超过 35%。

研究人员指出，他们的研究受限于随访时间和频率的变化。此外，可能存在对肝硬化和肝细胞癌的错误分类偏倚。最后，无法进行乙型肝炎病毒基因分型。

研究人员总结说：“虽然我们可能能够根据治疗结束的情况来辨别哪些患者更有可能实现功能性治愈，但仍不清楚需要采取什么以及何时采取先发制人的措施来预防严重的肝脏发作，这通常会导致造成严重甚至致命的后果。”

披露：作者声明与生物技术、制药和/或设备公司有隶属关系。请参阅原始参考资料以获取作者披露的完整列表。
参考

Hirode G、Choi HS、Chen C-H 等人。慢性乙型肝炎患者核苷（酸）类似物停药后的治疗外反应：一项国际、多中心、多种族队列（RETRACT-B 研究）。肠胃药。 2021 年 11 月 9 日在线发布。doi: 10.1053/j.gastro.2021.11.002

这篇文章最初出现在胃肠病学顾问上

StephenW

Nucleos(t)ide Analog Withdrawal in Patients With Chronic Hepatitis B


Off-therapy outcomes following the cessation of nucleos(t)ide analog (NA) therapy in patients with chronic hepatitis B (CHB) are dependent on hepatitis B surface antigen (HBsAg) levels at the time of discontinuation and patient race, according to the results of a study published in Gastroenterology.

Over 1500 patients with CHB who were positive for HBsAg, negative for Hepatitis B e antigen (HBeAg), and virally suppressed at the time of NA discontinuation were included. The international, multi-center cohort study excluded patients with hepatocellular carcinoma, coinfections such as Hepatitis C and/or HIV, and patients who had received treatment with pegylated- (PEG-) interferon within the previous 12 months.

The primary outcome was HBsAg loss, considered a functional cure of CHB. Secondary outcomes included virological relapse, defined as a single elevation of Hepatitis B DNA of at least 2000 IU/mL, retreatment, and liver-related concerns like hepatic decompensation.

In total, 1552 patients were included in the study. The mean age at the cessation of therapy was 52.9±11.3 years, 72.3% were men, 86.7% were Asian, and 11.3% were White. Most patients were treated with entecavir (63.2%) or tenofovir disoproxil fumarate (27.1%) prior to discontinuation of therapy.

White patients had a significantly higher cumulative probability of HBsAg loss compared with Asian patients (36.5% vs 10.9%; P <.001). Patients with HBsAg <100 IU/mL had the most favorable outcomes, independent of race. However, the HBsAg threshold needed at NA withdrawal to obtain a 30% cumulative probability of HBsAg loss was much higher for White compared with Asian patients, at <1000 IU/mL and <100 IU/mL, respectively.

Virologic relapse occurred in over 80% of patients by 48-months, with over half of patients requiring retreatment. Hepatic decompensation was rare, only occurring in 19/1552 patients, though the fatality rate of decompensation was over 35%.

Investigators note their study is limited by variations in follow-up visit length and frequency. Additionally, misclassification bias for cirrhosis and hepatocellular carcinoma may have been present. Finally, hepatitis B virus genotyping was unable to be performed.

Researchers concluded, “While we may be able to discern which patient is more likely to achieve functional cure based on end of therapy profiles, it is still unclear what, and when, preemptive measures need to be taken to prevent severe hepatic flares which often lead to severe or even fatal outcomes.”

Disclosure: The authors declared affiliations with biotech, pharmaceutical, and/or device companies. Pleases see the original reference for a full list of author disclosures.
Reference

Hirode G, Choi HS, Chen C-H, et al. Off-therapy response after nucleos(t)ide analogue withdrawal in patients with chronic hepatitis B: an international, multi-center, multi-ethnic cohort (RETRACT-B study). Gastroenterol. Published online November 9, 2021. doi: 10.1053/j.gastro.2021.11.002

This article originally appeared on Gastroenterology Advisor