乙型肝炎表面抗原异构体作为预测慢性丁型肝炎患者对布列韦肽病毒学反应的创新生物标志物
HBsAg Isoforms as Innovative Biomarkers in Predicting Virological Response to Bulevirtide in Patients With Chronic Hepatitis D.
作者信息
D'Anna Stefano, Salpini Romina, Degasperi Elisabetta, Piermatteo Lorenzo, Facchetti Floriana, Sambarino Dana, Torre Giulia, Borghi Marta, Anolli Maria Paola, Monico Sara, Svicher Valentina, Lampertico Pietro
机构信息
Department of Biology, University of Rome Tor Vergata, Rome, Italy.
Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
出版信息
Liver Int. 2025 May;45(5):e70094. doi: 10.1111/liv.70094.
BACKGROUND AND AIMS
HDV exploits HBV surface-protein (HBsAg) for entering into hepatocytes. HBsAg consists of 3 isoforms: Large- (L-HBs, predominantly present in virions and mediating binding to NTCP-receptor), Middle- (M-HBs) and Small-HBsAg (S-HBs). Here, we investigated the kinetics of HBs isoforms under bulevirtide treatment (BLV).
METHODS
67 consecutive patients with HDV-related compensated cirrhosis starting BLV 2 mg/day were enrolled. L-HBs, M-HBs and S-HBs were quantified by ad-hoc ELISAs in baseline and week 48 (W48) samples.
RESULTS
At baseline, median (IQR) HDV-RNA was 5.1 (4.3-5.7) log IU/mL while median (IQR) S-HBs, M-HBs and L-HBs levels were 3801 (1401-7462), 743 (211-1710) and 5 (1-13) ng/mL. At W48, virological responses (VR) were observed in 72% (48/67) of patients, while 25.4% (17/67) achieved undetectable HDV-RNA (11/17 with ALT-normalisation). A decline of S-HBs, M-HBs and L-HBs levels was observed in 51%, 63% and 31% of patients (median [IQR] decline: 961 [461-1985], 258 [68-626] and 4 [2-12] ng/mL). Notably, patients with undetectable HDV-RNA at W48 had baseline L-HBs and S-HBs levels lower than patients not achieving this end-point (1 [0.3-7] vs. 6 [2-13] ng/mL, p = 0.04 and 1570 [369-5185] vs. 4015 [1646-8687] ng/mL, p = 0.002). By AUROC, patients with baseline L-HBs < 3 ng/mL or S-HBs < 3400 ng/mL were more likely to achieve HDV-RNA undetectability at W48 (39.3% vs. 15.8%, p = 0.04 and 38.7% vs. 13.9%, p = 0.03). Furthermore, the combination of pre-treatment L-HBs < 3 ng/mL + HDV-RNA < 5logIU/mL and S-HBs < 3400 ng/mL + HDV-RNA < 5logIU/mL was the best predictor for achieving undetectable HDV-RNA at W48 (56.3% vs. 15.7%, p = 0.002 and 60% vs. 11%, p < 0.001).
CONCLUSIONS
Quantification of L-HBs and of S-HBs, along with HDV-RNA, may reflect the burden of circulating infectious virions in HBV/HDV co-infection, providing a promising tool to identify patients more likely to respond to BLV.
背景与目的
丁型肝炎病毒（HDV）利用乙型肝炎病毒表面蛋白（HBsAg）进入肝细胞。HBsAg由3种亚型组成：大蛋白（L-HBs，主要存在于病毒颗粒中并介导与NTCP受体的结合）、中蛋白（M-HBs）和小蛋白HBsAg（S-HBs）。在此，我们研究了布列韦肽（BLV）治疗下HBs亚型的动力学变化。
方法
纳入67例开始接受每日2mg BLV治疗的HDV相关代偿期肝硬化患者。通过特制酶联免疫吸附测定法（ELISA）对基线和第48周（W48）样本中的L-HBs、M-HBs和S-HBs进行定量分析。
结果
基线时，HDV-RNA中位数（四分位间距）为5.1（4.3 - 5.7）log IU/mL，而S-HBs、M-HBs和L-HBs水平中位数（四分位间距）分别为3801（1401 - 7462）、743（211 - 1710）和5（1 - 13）ng/mL。在W48时，72%（48/67）的患者出现病毒学应答（VR），25.4%（17/67）的患者HDV-RNA检测不到（17例中有11例谷丙转氨酶正常化）。51%、63%和31%的患者S-HBs、M-HBs和L-HBs水平下降（中位数[四分位间距]下降：961[461 - 1985]、258[68 - 626]和4[2 - 12]ng/mL）。值得注意的是，W48时HDV-RNA检测不到的患者基线L-HBs和S-HBs水平低于未达到此终点的患者（1[0.3 - 7]对6[2 - 13]ng/mL，p = 0.04；1570[369 - 5185]对4015[1646 - 8687]ng/mL，p = 0.002）。通过受试者工作特征曲线下面积（AUROC）分析，基线L-HBs < 3 ng/mL或S-HBs < 3400 ng/mL的患者在W48时更有可能实现HDV-RNA检测不到（分别为39.3%对15.8%，p = 0.04；38.7%对13.9%，p = 0.03）。此外，治疗前L-HBs < 3 ng/mL + HDV-RNA < 5 log IU/mL以及S-HBs < 3400 ng/mL + HDV-RNA < 5 log IU/mL的联合指标是W48时实现HDV-RNA检测不到的最佳预测指标（分别为56.3%对15.7%，p = 0.002；60%对11%，p < 0.001）。
结论
L-HBs和S-HBs与HDV-RNA的定量分析可能反映HBV/HDV合并感染中循环感染性病毒颗粒的负荷，为识别更可能对BLV有反应的患者提供了一个有前景的工具。
Zotero 插件