Li Jie, Sun Xizhen, Fang Jianting, Wang Chuanxi, Han Guoqing, Ren Wanhua
Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Ji'nan, Shandong 250021, China; Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, United States.
Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Ji'nan, Shandong 250021, China.
Clin Res Hepatol Gastroenterol. 2017 Dec;41(6):635-643. doi: 10.1016/j.clinre.2017.03.004. Epub 2017 Apr 21.
This study aimed to investigate the relationship between intrahepatic cccDNA and serum HBsAg in chronic Hepatitis B (CHB) patients with undetectable serum HBV DNA during antiviral therapy.
We investigated HBsAg serum levels and their relationship to intrahepatic total cccDNA and HBV DNA in CHB patients with undetectable serum HBV DNA during oral antiviral therapy. Intrahepatic cccDNA and HBV DNA quantitation were performed in the same needle biopsy material, while serum HBsAg, HBeAg and HBV DNA levels were measured in samples drawn on the day of the liver biopsy.
A total of 90 patients who had a liver biopsy were enrolled, including 80 patients with CHB and 10 patients with liver cirrhosis (LC). All the CHB patients were divided into HBeAg-positive and HBeAg-negative group. By using real-time PCR detection, we found that intrahepatic cccDNA and HBV DNA levels were higher in CHB patients than those in LC patients (Intrahepatic cccDNA: 6.15±1.19 vs. 6.12±0.36, HBV DNA: 7.26±0.49 vs. 5.59±0.45, both P<0.05). Intrahepatic cccDNA level was positively correlated with serum HBsAg in HBeAg-negative (r=0.66, P=0.02) and lower serum HBeAg (≤50S/CO) CHB patients (r=0.47, P=0.03), but not in higher serum HBeAg (>50S/CO) CHB patients (both P>0.05). In HBeAg negative patients, serum HBsAg level was correlated with intrahepatic total HBV DNA level (r=0.52, P=0.006). However, no relationship between HBsAg level and intrahepatic total HBV DNA level was found in HBeAg positive patients (both P>0.05).
Serum HBsAg can be used to predict intrahepatic cccDNA and HBV DNA level in CHB patients with low serum HBeAg statues, especially in HBeAg negative patients.
本研究旨在调查接受抗病毒治疗期间血清HBV DNA检测不到的慢性乙型肝炎（CHB）患者肝内cccDNA与血清HBsAg之间的关系。
我们调查了口服抗病毒治疗期间血清HBV DNA检测不到的CHB患者的HBsAg血清水平及其与肝内总cccDNA和HBV DNA的关系。在同一针穿刺活检材料中进行肝内cccDNA和HBV DNA定量，而在肝活检当天采集的样本中测量血清HBsAg、HBeAg和HBV DNA水平。
共纳入90例接受肝活检的患者，其中包括80例CHB患者和10例肝硬化（LC）患者。所有CHB患者分为HBeAg阳性组和HBeAg阴性组。通过实时PCR检测，我们发现CHB患者肝内cccDNA和HBV DNA水平高于LC患者（肝内cccDNA：6.15±1.19对6.12±0.36，HBV DNA：7.26±0.49对5.59±0.45，均P<0.05）。在HBeAg阴性（r=0.66，P=0.02）和血清HBeAg较低（≤50S/CO）的CHB患者中（r=0.47，P=0.03），肝内cccDNA水平与血清HBsAg呈正相关，但在血清HBeAg较高（>50S/CO）的CHB患者中无相关性（均P>0.05）。在HBeAg阴性患者中，血清HBsAg水平与肝内总HBV DNA水平相关（r=0.52，P=0.006）。然而，在HBeAg阳性患者中未发现HBsAg水平与肝内总HBV DNA水平之间的关系（均P>0.05）。
血清HBsAg可用于预测血清HBeAg水平较低的CHB患者，尤其是HBeAg阴性患者的肝内cccDNA和HBV DNA水平。
