Liver disease center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China.
Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment & Research, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China.
Int J Med Sci. 2022 May 9;19(5):858-866. doi: 10.7150/ijms.71737. eCollection 2022.
Correlations between serum viral markers and intrahepatic cccDNA in patients undergoing long-term nucleos(t)ide analogues (NAs) treatment haven't been fully explored. In this study, we evaluate the correlation between intrahepatic cccDNA and other serum viral markers and intrahepatic HBV DNA in HBeAg positive chronic hepatitis B (CHB) patients during 60-month treatment with NAs. Fifty-four HBeAg positive CHB patients received long-term NAs treatment were included in this study. Serial serum samples were regularly collected and quantitatively analyzed for HBsAg, HBV DNA, HBV RNA and HBcrAg. Histological samples from liver biopsy at baseline and month 60 were analyzed for intrahepatic HBV DNA and cccDNA. At baseline, serum HBV DNA plus RNA was positively associated with intrahepatic cccDNA in multivariate regression analysis (β=0.205, <0.001). In the correlation analysis between cccDNA and serum viral markers, HBV DNA plus RNA had the highest correlation coefficient (r=0.698, <0.001), followed by serum HBV DNA (r=0.641, <0.001), HBV RNA (r=0.590, <0.001), and HBcrAg (r=0.564, <0.001). At month 60, correlations between these serum viral markers and cccDNA were not observed (>0.05). Multivariate regression analysis showed that only the decreased HBV DNA plus RNA was positively associated with cccDNA decline (β=0.172, =0.006). Changes of HBV DNA plus RNA (r=0.525, =0.001) was better correlated with cccDNA decline as compared to HBV RNA (r=0.384, =0.008), HBV DNA (r=0.431, =0.003), and HBsAg (r=0.342, =0.029). Serum HBV DNA plus RNA better correlated with intrahepatic cccDNA than other viral makers before and during NAs treatment in HBeAg positive CHB patients.
血清病毒标志物与接受长期核苷（酸）类似物（NAs）治疗的患者肝内cccDNA 之间的相关性尚未得到充分探讨。本研究旨在评估 HBeAg 阳性慢性乙型肝炎（CHB）患者在接受 NAs 治疗 60 个月期间，肝内 cccDNA 与其他血清病毒标志物和肝内 HBV DNA 之间的相关性。
本研究纳入了 54 例接受长期 NAs 治疗的 HBeAg 阳性 CHB 患者。定期采集连续的血清样本，定量分析 HBsAg、HBV DNA、HBV RNA 和 HBcrAg。基线和 60 个月时的肝活检组织样本用于分析肝内 HBV DNA 和 cccDNA。
在多变量回归分析中，基线时血清 HBV DNA 加 RNA 与肝内 cccDNA 呈正相关（β=0.205，<0.001）。在 cccDNA 与血清病毒标志物的相关性分析中，HBV DNA 加 RNA 的相关系数最高（r=0.698，<0.001），其次是血清 HBV DNA（r=0.641，<0.001）、HBV RNA（r=0.590，<0.001）和 HBcrAg（r=0.564，<0.001）。60 个月时，这些血清病毒标志物与 cccDNA 之间无相关性（>0.05）。多变量回归分析显示，仅 HBV DNA 加 RNA 的降低与 cccDNA 下降呈正相关（β=0.172，=0.006）。与 HBV RNA（r=0.384，=0.008）、HBV DNA（r=0.431，=0.003）和 HBsAg（r=0.342，=0.029）相比，HBV DNA 加 RNA 的变化（r=0.525，=0.001）与 cccDNA 下降的相关性更好。
在 HBeAg 阳性 CHB 患者中，血清 HBV DNA 加 RNA 在 NAs 治疗前后与肝内 cccDNA 的相关性优于其他病毒标志物。
