治疗结束时乙肝核心相关抗原水平较高预示着核苷（酸）类似物治疗停药后肝炎发作。

High end-of-treatment hepatitis B core-related antigen levels predict hepatitis flare after stopping nucleot(s)ide analogue therapy.

作者信息

Hume Simon J, Wong Danny K, Yuen Man-Fung, Jackson Kathy, Bonanzinga Sara, Vogrin Sara, Hall Samuel A L, Burns Gareth S, Desmond Paul V, Sundararajan Vijaya, Ratnam Dilip, Levy Miriam T, Lubel John S, Nicoll Amanda J, Strasser Simone I, Sievert William, Ngu Meng C, Sinclair Marie, Meredith Christopher, Matthews Gail, Revill Peter A, Littlejohn Margaret, Bowden Scott, Visvanathan Kumar, Holmes Jacinta A, Thompson Alexander J

机构信息

St Vincent's Hospital Melbourne, Fitrozy, Victoria, Australia.

Department of Medicine, University of Melbourne, Parkville, Victoria, Australia.

出版信息

Liver Int. 2024 Oct;44(10):2605-2614. doi: 10.1111/liv.16029. Epub 2024 Jul 15.

DOI:10.1111/liv.16029

PMID:39007640

Abstract

BACKGROUND AND AIMS

Accurate biomarkers to predict outcomes following discontinuation of nucleos(t)ide analogue (NA) therapy are needed. We evaluated serum hepatitis B core-related antigen (HBcrAg) level as a biomarker for predicting outcomes after NA discontinuation.

METHODS

Patients with HBeAg-negative chronic hepatitis B (CHB) without cirrhosis were enrolled in a prospective trial evaluating clinical outcomes until 96 weeks after NA discontinuation. End of treatment (EOT) and off-treatment levels of serum HBcrAg, HBsAg, HBV RNA and HBV DNA were used to predict key clinical outcomes including hepatitis flare (ALT ≥5 × ULN and HBV DNA > 2000 IU/mL). The SCALE-B score was calculated for the purposes of model validation.

RESULTS

HBcrAg was tested amongst 65 participants. The median age was 54 years, 54% were male and 83% were Asian. HBcrAg was detectable in 86% patients. HBcrAg level ≥4 log U/mL at EOT was predictive of hepatitis flare [8/10 (80%) vs. 17/55 (31%), p = .001]. The presence of either HBcrAg ≥4 log U/mL or detectable HBV RNA at EOT predicted for both biochemical relapse and hepatitis flare. The SCALE-B model at EOT predicted for virological relapse, biochemical relapse, hepatitis flare and HBsAg loss in this cohort. An increase in the serum HBcrAg level off-treatment was also associated with hepatitis flare. No participant with EOT HBcrAg level ≥4 log U/mL achieved HBsAg loss.

CONCLUSIONS

High levels of serum HBcrAg predict for hepatitis flare after stopping NA therapy and low likelihood of HBsAg loss at week 96. People with high levels of serum HBcrAg are not suitable candidates for NA discontinuation.

摘要

背景与目的

需要准确的生物标志物来预测核苷（酸）类似物（NA）治疗停药后的结局。我们评估了血清乙肝核心相关抗原（HBcrAg）水平作为预测NA停药后结局的生物标志物。

方法

将无肝硬化的HBeAg阴性慢性乙型肝炎（CHB）患者纳入一项前瞻性试验，评估NA停药后直至96周的临床结局。使用治疗结束（EOT）时及停药后的血清HBcrAg、HBsAg、HBV RNA和HBV DNA水平来预测关键临床结局，包括肝炎发作（ALT≥5×ULN且HBV DNA>2000 IU/mL）。为进行模型验证计算了SCALE-B评分。

结果

对65名参与者进行了HBcrAg检测。中位年龄为54岁，54%为男性，83%为亚洲人。86%的患者可检测到HBcrAg。EOT时HBcrAg水平≥4 log U/mL可预测肝炎发作[8/10（80%）对17/55（31%），p = 0.001]。EOT时HBcrAg≥4 log U/mL或可检测到HBV RNA可预测生化复发和肝炎发作。EOT时的SCALE-B模型可预测该队列中的病毒学复发、生化复发、肝炎发作和HBsAg消失。停药后血清HBcrAg水平升高也与肝炎发作相关。EOT时HBcrAg水平≥4 log U/mL的参与者无一人实现HBsAg消失。