停用核苷类似物治疗的慢性乙型肝炎患者复发的预测因子

StephenW

Predictors of Relapse in Patients With Chronic Hepatitis B Who Discontinue Nucleos(t)ide Analogue Therapy


End-of-therapy hepatitis B surface antigen (HBsAg) levels, duration of consolidation therapy, and cirrhosis status are key determinants of relapse in patients with chronic hepatitis B (CHB) who discontinue nucleos(t)ide analogue (NA) therapy, according to study results published in Clinical Infectious Diseases.

In this retrospective study, researchers analyzed data from 488 patients with CHB to identify predictors of relapse in those who discontinued NAs and to determine if existing rules for stopping NA therapy can be improved. Virologic relapse was defined as serum hepatitis B virus DNA with a value of at least 2000 IU/mL after stopping treatment, and clinical relapse constituted virologic relapse along with alanine aminotransferase greater than 2 times the upper limit of normal. Researchers used the Asian Pacific Association for the Study of the Liver, European Association for the Study of the Liver, and American Association for the Study of Liver Diseases guidelines to assess whether NA treatment was stopped.

According to the Asian Pacific Association for the Study of the guidelines, 40% of patients (n=195) stopped antiviral therapy. Once NA therapy was stopped, the median follow-up period was 73.3 months. Follow-up at 1, 2, 5, and 10 year occurred in 93.0% (n=454), 84.2% (n=411), 59.0% (n=288), and 19.7% (n=96) of patients, respectively. A comparison of the 1, 2, 5, and 10-year cumulative rates of virologic relapse (54.1%, 65.0%, 73.5%, and 76.1%, respectively) and clinical relapse (33.2%, 45.0%, 54.7%, and 56.6%, respectively) showed a steep rise until year 2. Thus, researchers further analyzed the 2-year virologic and clinical relapse data.


In hepatitis B e antigen (HBeAg)-positive patients (n=262), end-of-therapy HBsAg levels (hazard ratio [HR], 1.93; 95% CI, 1.42-2.61) and consolidation duration of therapy of more than 2 years (HR, 0.31; 95% CI, 0.17-0.58) were independent predictors of virologic relapse; only consolidation duration of therapy of more than 2 years (HR, 0.49; 95% CI, 0.26-0.93) was an independent predictor of clinical relapse. Regardless of stopping rules, virologic relapse rate was significantly lower in patients attaining HBsAg levels less than or equal to 560 IU/mL than in those not attaining this level (with stopping rule, P =.007; without stopping rule, P =.027).


For HBeAg-negative patients (n=226), only HBsAg level was an independent predictor of both virologic (HR, 1.61; 95% CI, 1.24-2.11) and clinical relapse (HR, 1.16; 95% CI, 1.10-2.36). The virologic relapse rate was significantly lower when HBsAg levels was less than or equal to 800 IU/mL than in those not attaining this level when not meeting the stopping rule (P =.031) and only marginal when meeting the stopping rule (P =.096).

However, despite HBsAg levels of at least 800 IU/mL in HBeAg-negative patients, virologic relapse rates were significantly higher in patients with cirrhosis than in those without cirrhosis (P =.026). Cirrhosis was the only predictor of 2-year virologic relapse (P =.031). This finding supports the specific recommendations by the European Association for the Study of the Liver and American Association for the Study of Liver Diseases guidelines for continuing antiviral therapy in HBeAg-negative patients with cirrhosis.

Combining low HBsAg levels, consolidation therapy for more than 2 years, and ensuring that patients with cirrhosis stay on NA therapy even with low HBsAg levels not only significantly reduced post-treatment relapse but also improved performance of the stopping rules. As such, these “parameters should be added to the components of the NA stopping rules,” the researchers concluded.

Since this study only included patients from Korea mostly treated with lamivudine and entecavir, further studies are necessary to validate findings for different ethnicities and patients treated with tenofovir. In addition, researchers will need to further evaluate the optimal cut-off values of HBsAg levels.

Reference

Song DS, Jang JW, Yoo SH, et al. Improving the prediction of relapse after nucleos(t)ide analogue discontinuation in patients with chronic hepatitis B. Clin Infect Dis. Published online January 8, 2021. doi:10.1093/cid/ciab007

StephenW

停用核苷类似物治疗的慢性乙型肝炎患者复发的预测因子


治疗结束后，乙型肝炎表面抗原（HBsAg）水平，巩固治疗的持续时间和肝硬化状态是停用核苷酸（t）ide类似物（NA）治疗的慢性乙型肝炎（CHB）患者复发的关键因素。研究发表在《临床传染病》上的结果。

在这项回顾性研究中，研究人员分析了488例CHB患者的数据，以确定那些停用NAs的复发预测因素，并确定是否可以改善停止NA治疗的现有规则。病毒学复发的定义是停止治疗后血清乙型肝炎病毒DNA的值至少为2000 IU / mL，临床复发是病毒学复发，同时丙氨酸转氨酶大于正常上限的2倍。研究人员使用亚太太平洋肝病研究协会，欧洲肝病研究协会和美国肝病研究协会指南评估是否停止了NA治疗。

根据该指南的亚太研究协会，40％的患者（n = 195）停止了抗病毒治疗。一旦停止NA治疗，中位随访期为73.3个月。在1年，2年，5年和10年时，分别有93.0％（n = 454），84.2％（n = 411），59.0％（n = 288）和19.7％（n = 96）的患者进行了随访，分别。 1、2、5和10年累计病毒学复发率（分别为54.1％，65.0％，73.5％和76.1％）和临床复发率（33.2％，45.0％，54.7％和56.6）的比较分别增长至2年。因此，研究人员进一步分析了2年的病毒学和临床复发数据。


在乙型肝炎e抗原（HBeAg）阳性患者中（n = 262），治疗结束后HBsAg水平（危险比[HR]为1.93； 95％CI为1.42-2.61），合并治疗的持续时间超过2年（HR，0.31； 95％CI，0.17-0.58）是病毒学复发的独立预测因子；只有合并治疗持续时间超过2年（HR，0.49； 95％CI，0.26-0.93）是临床复发的独立预测因子。不论停止规则如何，HBsAg水平低于或等于560 IU / mL的患者的病毒学复发率显着低于未达到该水平的患者（有停止规则，P = .007；没有停止规则，P = .027 ）。


对于HBeAg阴性患者（n = 226），只有HBsAg水平是病毒学（HR，1.61; 95％CI，1.24-2.11）和临床复发（HR，1.16; 95％CI，1.10-2.36）的独立预测指标。 。当HBsAg水平小于或等于800 IU / mL时，病毒学复发率显着低于未达到停止水平的患者（P = .031），而只有达到停止水平的患者（P = .096）。

然而，尽管HBeAg阴性患者的HBsAg水平至少为800 IU / mL，但肝硬化患者的病毒学复发率显着高于非肝硬化患者（P = .026）。肝硬化是2年病毒学复发的唯一预测因子​​（P = .031）。这一发现支持了欧洲肝病研究协会和美国肝病研究协会针对HBeAg阴性肝硬化患者继续抗病毒治疗的指南的具体建议。

结合低HBsAg水平，巩固治疗2年以上，并确保即使低HBsAg水平的肝硬化患者也继续接受NA治疗，不仅显着降低了治疗后的复发率，而且改善了停药规则。因此，研究人员总结说，这些“参数应添加到NA停止规则的组成部分中”。

由于该研究仅包括来自韩国的主要接受拉米夫定和恩替卡韦治疗的患者，因此有必要进行进一步的研究以验证不同种族和替诺福韦治疗的患者的发现。此外，研究人员将需要进一步评估HBsAg水平的最佳临界值。

参考

Song DS，Jang JW，Yo SH等。改善慢性乙型肝炎患者核苷酸（t）ide类似物停药后复发的预测。在线发布于2021年1月8日。doi：10.1093 / cid / ciab007

乙肝人1949

职称沦文

newchinabok

乙肝人1949 发表于 2021-4-3 14:27
职称沦文

这波新药大多数失败，除了vir几个项目，十年都难看到希望，对有些人治愈也没什么意义了。就算Rnai+干挠素能成功，用得起也是十年后了。十年后有多少人变老，干挠素能用吗？有效吗？不良反应受得了吗？时不待我了。人一生几个十年，吾辈能不能看到治愈那天很难说了

乙肝人1949

嗯啦，积极准备上干扰素