Hepatology, Medicine, University of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia ; Digestive Disease and GI Oncology Center, Medistra Hospital, Jakarta, Indonesia.
Victorian Infectious Disease Reference Laboratory, Melbourne, Australia.
United European Gastroenterol J. 2014 Apr;2(2):99-107. doi: 10.1177/2050640614525151.
Clinical use of hepatitis B viral (HBV) quantitative seromarker\s remains questionable since it is not precisely known whether they represent intrahepatic viral replication. Covalently closed circular DNA (cccDNA), relaxed circular DNA (rcDNA), and pregenomic RNA (pgRNA) are more likely to represent active HBV replication and their measurement can be used to derive virion productivity (VP; rcDNA/cccDNA), subviral particle (SVP) productivity (quantitative HBsAg/cccDNA), and replicative activity (RA; pgRNA/cccDNA). These can be used to compare relative HBV replication between HBeAg-negative and -positive patients.
To study the clinical significance of intrahepatic HBV replication phenomenon between HBeAg-negative and -positive patients and its correlation with quantitative HBV seromarkers.
This was a prospective study between January 2010 and December 2011. Study subjects were naive chronic hepatitis B patients from Cipto Mangunkusumo and Medistra Hospitals. All patient samples underwent liver biochemistry and HBV seromarkers testing (HBeAg, quantitative HBsAg and HBV DNA levels), and patients underwent liver biopsy. Stored liver specimens were analysed for intrahepatic rcDNA, cccDNA, and pgRNA with quantification performed by real-time PCR. Comparison of HBV markers between HBsAg-positive and -negative patients was carried out using the Mann-Whitney U-test. Pearson's correlation test was performed among HBV intrahepatic and seromarkers using their log-transformed values.
A total of 104 patients were enrolled in this study; 54 (51.9%) were male. Patients' mean age was 41.9 ± 11.63 years (range 19-70 years). Sixty-one patients (58.7%) were HBeAg-negative. All HBV markers were significantly higher in HBeAg-positive than HBeAg-negative patients, except for SVP productivity and RA. Serum HBV DNA was strongly correlated with intrahepatic total HBV DNA (r = 0.771), cccDNA (r = 0.774), and rcDNA (r = 0.780) while serum quantitative HBsAg showed only moderate correlation with intrahepatic total DNA (r = 0.671), cccDNA (r = 0.632), rcDNA (r = 0.675), and SVP productivity (r = 0.557).
Serum HBV DNA concentration and quantitative HBsAg might not accurately predict intrahepatic viral activity. Virion and SVP production do not occur in parallel with replicative activity.
乙型肝炎病毒（HBV）定量血清标志物的临床应用仍存在疑问，因为尚不清楚它们是否代表肝内病毒复制。共价闭合环状 DNA（cccDNA）、松弛环状 DNA（rcDNA）和前基因组 RNA（pgRNA）更可能代表活跃的 HBV 复制，其测量可用于推导病毒产量（rcDNA/cccDNA）、亚病毒颗粒（SVP）产量（定量 HBsAg/cccDNA）和复制活性（pgRNA/cccDNA）。这些可用于比较 HBeAg 阴性和阳性患者之间的 HBV 复制相对情况。
研究 HBeAg 阴性和阳性患者之间肝内 HBV 复制现象的临床意义及其与定量 HBV 血清标志物的相关性。
这是一项 2010 年 1 月至 2011 年 12 月的前瞻性研究。研究对象为 Cipto Mangunkusumo 和 Medistra 医院的初治慢性乙型肝炎患者。所有患者样本均进行肝功能和 HBV 血清标志物检测（HBeAg、定量 HBsAg 和 HBV DNA 水平），并进行肝活检。储存的肝标本采用实时 PCR 进行 rcDNA、cccDNA 和 pgRNA 的定量分析。使用 Mann-Whitney U 检验比较 HBsAg 阳性和阴性患者之间的 HBV 标志物。使用其对数转换值对 HBV 肝内和血清标志物进行 Pearson 相关性检验。
本研究共纳入 104 例患者，其中 54 例（51.9%）为男性。患者的平均年龄为 41.9±11.63 岁（19-70 岁）。61 例（58.7%）为 HBeAg 阴性。与 HBeAg 阴性患者相比，所有 HBV 标志物在 HBeAg 阳性患者中均显著升高，除 SVP 产量和 RA 外。血清 HBV DNA 与肝内总 HBV DNA（r=0.771）、cccDNA（r=0.774）和 rcDNA（r=0.780）高度相关，而血清定量 HBsAg 仅与肝内总 DNA（r=0.671）、cccDNA（r=0.632）、rcDNA（r=0.675）和 SVP 产量（r=0.557）中度相关。
血清 HBV DNA 浓度和定量 HBsAg 可能无法准确预测肝内病毒活性。病毒和 SVP 的产生与复制活性并不平行。
