Combining hepatitis B core-related and surface antigens at end of nucleos(t)ide analogue treatment to predict off-therapy relapse risk
Combining hepatitis B core-related and surface antigens at end of nucleos(t)ide analogue treatment to predict off-therapy relapse risk
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DOI：
10.1111/apt.15058
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发表时间：
2019-01-01
影响因子：
7.6
通讯作者：
Chang, Chi-Yang
中科院分区：
文献类型：
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作者：
Hsu, Yao-Chun;Nguyen, Mindie H.;Chang, Chi-Yang
背景 对于用于评估慢性乙型肝炎 (CHB) 中停用核苷（酸）类似物 (NA) 的风险的便利生物标志物的需求仍未得到满足。目的 研究乙型肝炎核心相关抗原 (HBcrAg) 是否独立于表面抗原 (HBsAg)，以预测 NA 停止的风险。方法 这项前瞻性多中心研究纳入了 135 名慢性乙型肝炎患者，他们在中位病毒缓解 25.2 个月后停用恩替卡韦或替诺福韦。所有患者均在 HBeAg 阴性且病毒 DNA 检测不到的情况下停止 NA，然后观察临床复发和 HBsAg 消失情况。使用 Cox 比例风险模型探索包括 HBsAg 和 HBcrAg 水平在内的预测因子，并进行加权以制定风险评分。结果 在中位随访 25.9 个月期间，分别有 66 名患者和 8 名患者出现临床复发和 HBsAg 消失，5 年累积发生率分别为 56.1% (95% CI 46.7-66.0%) 和 8.8% (95% CI 4.3-17.4%)。 HBcrAg 以及 HBsAg、年龄、ALT 和替诺福韦的使用是独立的复发预测因素。替诺福韦使用的评分 (SCALE-B) 通过 35*HBsAg (log IU/mL) + 20*HBcrAg (log U/mL) + 2* 年龄 (年) + ALT (U/L) + 40 等式计算。 1、2、3、4 和 5 年临床复发的一致性率分别为 0.87、0.88、0.87、0.85 和 0.90。此外，HBsAg 消失仅发生在评分预测的低风险患者中。结论 血清 HBcrAg 和 HBsAg 水平是 NA 外复发的独立预测因子，可纳入风险评分中以指导 CHB 患者停止治疗。
Background There remains an unmet need for convenient biomarkers to assess the risks of discontinuing nucleos(t)ide analogues (NAs) in chronic hepatitis B (CHB). Aim To investigate if hepatitis B core-related antigen (HBcrAg) is an independent of surface antigen (HBsAg) for risk prediction of NA cessation. Methods This prospective multicentre study enrolled 135 CHB patients who stopped entecavir or tenofovir after achieving viral remission for a median of 25.2 months. All patients stopped NA with negative HBeAg and undetectable viral DNA, and were then observed for clinical relapse and HBsAg loss. Predictors including HBsAg and HBcrAg levels were explored using Cox proportional hazard model and weighted to develop a risk score. Results During a median follow-up of 25.9 months, clinical relapse and HBsAg loss occurred in 66 and eight patients, respectively, with a 5-year cumulative incidence of 56.1% (95% CI 46.7-66.0%) and 8.8% (95% CI 4.3-17.4%), respectively. HBcrAg was an independent relapse predictor, as well as HBsAg, age, ALT and tenofovir use. A score (SCALE-B) was calculated by the equation of 35*HBsAg (log IU/mL) + 20*HBcrAg (log U/mL) + 2*age (year) + ALT (U/L) + 40 for tenofovir use. The concordance rates for clinical relapse were 0.87, 0.88, 0.87, 0.85 and 0.90 at 1, 2, 3, 4 and 5 years, respectively. Moreover, HBsAg loss occurred exclusively in low-risk patients predicted by the score. Conclusions Serum HBcrAg and HBsAg levels were independent predictors of off-NA relapse and can be factored into a risk score to guide treatment cessation in patients with CHB.