Caviglia Gian Paolo, Abate Maria Lorena, Noviello Daniele, Olivero Antonella, Rosso Chiara, Troshina Giulia, Ciancio Alessia, Rizzetto Mario, Saracco Giorgio Maria, Smedile Antonina
Department of Medical Sciences, University of Turin, Turin, Italy.
Department of Gastroenterology, Città della Salute e della Scienza Hospital, Turin, Italy.
Hepatol Res. 2017 Jul;47(8):747-754. doi: 10.1111/hepr.12811. Epub 2016 Sep 27.
The aim of this study was to evaluate the correlation between hepatitis B core-related antigen (HBcrAg) and hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) levels, and to investigate HBcrAg kinetics during nucleos(t)ide analogue (NA) or pegylated-interferon (PEG-IFN)-α treatment in a cohort of chronic hepatitis B (CHB) genotype D patients.
One hundred thirty eight sequential serum samples were collected from 28 hepatitis B e antigen-negative CHB genotype D patients (20 men and 8 women; median age, 54 years [range, 47-58 years]) who underwent NA (n = 20) or PEG-IFN-α (n = 8) treatment. Serum HBcrAg levels were determined by chemiluminescent enzyme immunoassay. Longitudinal analysis was carried out at 6, 12, 24, and 36 months after NA treatment initiation and at 6, 12, and 18 months and at follow-up month 6 after PEG-IFN-α treatment.
Basal HBcrAg levels were 4.7 ± 1.8 Log U/mL and 3.3 ± 1.6 Log U/mL in NA- and PEG-IFN-α-treated patients, respectively. Hepatitis B core-related antigen showed a moderate correlation with HBV DNA (r = 0.498, P < 0.0001) and no correlation with HBsAg (r = 0.192, P = 0.0669). In serial serum samples, a significant HBcrAg reduction was observed only in patients receiving NA (P = 0.019). In these patients, we observed a group (n = 12) with an early HBcrAg decline to undetectable levels between months 6-12, whereas the other group (n = 8) still had detectable HBcrAg at month 36 (4.4 ± 0.6 Log U/mL), independently from HBV DNA and HBsAg kinetics.
Serum HBcrAg correlates with HBV DNA levels, most likely through expression of viral replication activity. We observed two different HBcrAg kinetics in NA-treated patients, suggesting different relapse risk related to NA cessation. Further studies on larger patient cohorts will elucidate the role of HBcrAg in the safe discontinuation of NA in CHB genotype D patients.
本研究旨在评估乙型肝炎核心相关抗原（HBcrAg）与乙型肝炎病毒（HBV）DNA及乙型肝炎表面抗原（HBsAg）水平之间的相关性，并在一组慢性乙型肝炎D基因型（CHB）患者队列中，研究核苷（酸）类似物（NA）或聚乙二醇干扰素（PEG-IFN）-α治疗期间HBcrAg的动态变化。
从28例接受NA（n = 20）或PEG-IFN-α（n = 8）治疗的乙型肝炎e抗原阴性的CHB D基因型患者（20例男性和8例女性；中位年龄54岁[范围47 - 58岁]）中，连续收集138份血清样本。采用化学发光酶免疫分析法测定血清HBcrAg水平。在开始NA治疗后的6、12、24和36个月以及PEG-IFN-α治疗后的6、12和18个月及随访第6个月进行纵向分析。
在接受NA和PEG-IFN-α治疗的患者中，基础HBcrAg水平分别为4.7±1.8 Log U/mL和3.3±1.6 Log U/mL。乙型肝炎核心相关抗原与HBV DNA呈中度相关（r = 0.498，P < 0.0001），与HBsAg无相关性（r = 0.192，P = 0.0669）。在系列血清样本中，仅在接受NA治疗的患者中观察到HBcrAg显著降低（P = 0.019）。在这些患者中，我们观察到一组（n = 12）在6 - 12个月期间HBcrAg早期下降至不可检测水平，而另一组（n = 8）在36个月时仍有可检测的HBcrAg（4.4±0.6 Log U/mL），与HBV DNA和HBsAg的动态变化无关。
血清HBcrAg与HBV DNA水平相关，很可能是通过病毒复制活性的表达实现的。我们在接受NA治疗的患者中观察到两种不同的HBcrAg动态变化，提示与NA停药相关的不同复发风险。对更大患者队列的进一步研究将阐明HBcrAg在CHB D基因型患者安全停用NA中的作用。
