Brancaccio Giuseppina, Salpini Romina, Piermatteo Lorenzo, Surdo Matteo, Fini Vanessa, Colagrossi Luna, Cantone Marco, Battisti Arianna, Oda Yasunori, Di Carlo Domenico, Ceccherini-Silberstein Francesca, Perno Carlo Federico, Gaeta Giovanni Battista, Svicher Valentina
Infectious Diseases, University Hospital of Padua, 35128 Padua, Italy.
Department of Experimental Medicine, Tor Vergata University, 00133 Rome, Italy.
Microorganisms. 2021 Apr 2;9(4):752. doi: 10.3390/microorganisms9040752.
Hepatitis B virus (HBV) contains three surface glycoproteins-Large-HBs (L-HBs), Middle-HBs (M-HBs), and Small-HBs (S-HBs), known to contribute to HBV-driven pro-oncogenic properties. Here, we examined the kinetics of HBs-isoforms in virologically-suppressed patients who developed or did not develop hepatocellular carcinoma (HCC). This study enrolled 30 chronically HBV-infected cirrhotic patients under fully-suppressive anti-HBV treatment. Among them, 13 patients developed HCC. Serum samples were collected at enrolment (T0) and at HCC diagnosis or at the last control for non-HCC patients (median (range) follow-up: 38 (12-48) months). Ad-hoc ELISAs were designed to quantify L-HBs, M-HBs and S-HBs (Beacle). At T0, median (IQR) levels of S-HBs, M-HBs and L-HBs were 3140 (457-6995), 220 (31-433) and 0.2 (0-1.7) ng/mL. No significant differences in the fraction of the three HBs-isoforms were noticed between patients who developed or did not develop HCC at T0. On treatment, S-HBs showed a >25% decline or remained stable in a similar proportion of HCC and non-HCC patients (58.3% of HCC- vs. 47.1% of non-HCC patients, = 0.6; 25% of HCC vs. 29.4% of non-HCC, = 0.8, respectively). Conversely, M-HBs showed a >25% increase in a higher proportion of HCC compared to non-HCC patients (50% vs. 11.8%, = 0.02), in line with M-HBs pro-oncogenic role reported in in vitro studies. No difference in L-HBs kinetics was observed in HCC and non-HCC patients. In conclusion, an increase in M-HBs levels characterizes a significant fraction of HCC-patients while under prolonged HBV suppression and stable/reduced total-HBs. The role of M-HBs kinetics in identifying patients at higher HCC risk deserves further investigation.
乙型肝炎病毒（HBV）包含三种表面糖蛋白——大乙肝表面抗原（L-HBs）、中乙肝表面抗原（M-HBs）和小乙肝表面抗原（S-HBs），已知它们会促成HBV驱动的促癌特性。在此，我们研究了在病毒学抑制的患者中，已发生或未发生肝细胞癌（HCC）的患者体内乙肝表面抗原异构体的动力学变化。本研究纳入了30例接受完全抑制性抗HBV治疗的慢性HBV感染肝硬化患者。其中，13例患者发生了HCC。在入组时（T0）以及HCC诊断时或非HCC患者的最后一次对照时（中位（范围）随访时间：38（12 - 48）个月）采集血清样本。设计了专门的酶联免疫吸附测定法（ELISA）来定量检测L-HBs、M-HBs和S-HBs（Beacle）。在T0时，S-HBs、M-HBs和L-HBs的中位（四分位间距）水平分别为3140（457 - 6995）、220（31 - 433）和0.2（0 - 1.7）ng/mL。在T0时，发生或未发生HCC的患者之间，三种乙肝表面抗原异构体的比例没有显著差异。在治疗过程中，S-HBs在相似比例的HCC患者和非HCC患者中出现>25%的下降或保持稳定（HCC患者为58.3%，非HCC患者为47.1%，P = 0.6；HCC患者为25%，非HCC患者为29.4%，P = 0.8）。相反，与非HCC患者相比，M-HBs在更高比例的HCC患者中出现>25%的增加（50%对11.8%，P = 0.02），这与体外研究报道的M-HBs的促癌作用一致。在HCC患者和非HCC患者中未观察到L-HBs动力学的差异。总之，在长期HBV抑制且总乙肝表面抗原稳定/降低的情况下，M-HBs水平升高是相当一部分HCC患者的特征。M-HBs动力学在识别HCC风险较高患者中的作用值得进一步研究。
