Journal of HepatologyVolume 68, Issue 1, January 2018, Pages 16-24
Research Article
Relationship between serum HBV-RNA levels and intrahepatic viral as well as histologic activity markers in entecavir-treated patientsAuthor links open overlay panelJingWang1†YiqiYu1†GuojunLi2†ChuanShen3†ZhefengMeng4†JianmingZheng1†YanhongJia3ShaolongChen1XiaoZhang5MengqiZhu1JiangjiangZheng6ZhangzhangSong2JingWu1LingyunShao1PeiyuQian4XiaonaMao7XuanyiWang89YuxianHuang1CaiyanZhao3JimingZhang1ChaoQiu1489WenhongZhang11Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China2Department of Hepatology, The Second Hospital of Yinzhou of Ningbo, Ningbo, China3Department of Infectious Diseases, The Third Hospital of Hebei Medical University, Shijiazhuang, China4Minhang Hospital, Fudan University, Shanghai, China5Continuing Education Office, Healthy School of Huangpu District, Shanghai, China6Department of Pathology, The Second Hospital of Yinzhou of Ningbo, Ningbo, China7Department of Clinical Laboratory, The Second Hospital of Yinzhou of Ningbo, Ningbo, China8Institutes of Biomedical Sciences, Fudan University, Shanghai, China9Key Laboratory of Medical Molecular Virology, Fudan University, Shanghai, China
Received 23 February 2017, Revised 17 August 2017, Accepted 18 August 2017, Available online 21 September 2017.
https://doi.org/10.1016/j.jhep.2017.08.021Get rights and content
Referred to byJing Wang, Yiqi Yu, Zhefeng Meng, Chuan Shen, Miaoqu Zhang, Peiyu Qian, Caiyan Zhao, Xuanyi Wang, Yuxian Huang, Jiming Zhang, Chao Qiu, Wenhong Zhang
Reply to: “HBV RNA virion-like particles produced under nucleos(t)ide analogues treatment are mainly replication-deficient”Journal of Hepatology, Available online 4 November 2017, Pages
PDF (166KB)Jie Wang, Qiuju Sheng, Yang Ding, Ran Chen, Xiaofeng Sun, Xiangmei Chen, Xiaoguang Dou, Fengmin Lu
HBV RNA virion-like particles produced under nucleos(t)ide analogues treatment are mainly replication-deficientJournal of Hepatology, Available online 4 November 2017, Pages
PDF (454KB)
Highlights•Detectable HBV-RNA in serum of NUC successfully treated patients. •Serum HBV-RNA is indicative of the transcriptional activity of cccDNA. •Quasispecies of serum HBV-RNA and intrahepatic HBV-RNA are similar. •Levels of HBV-RNA correlate with histopathological scores.
Background & AimsIn diagnostics, serum hepatitis B virus (HBV)-RNA levels are valuable when the HBV-DNA load in circulation is effectively suppressed by nucleos(t)ide analogue (NUC) therapy. This study aimed to determine the intrahepatic viral replication activity reflected in serum HBV-RNA and whether HBV-RNA contributes to liver histological changes in patients treated with NUC.
MethodsA cross-sectional set of serum and liver biopsy samples was obtained from patients treated with entecavir, who had undetectable levels of serum HBV-DNA. The correlations between serum HBV-RNA concentration and levels of peripheral and intrahepatic viral replicative forms, as well as histological scores, were analyzed. Quasispecies of serum HBV-RNA and intrahepatic viral replicative forms were examined by deep sequencing. HBV-RNA-positive hepatocytes were visualized by in situ hybridization.
ResultsSerum HBV-RNA was detected in 35 of 47 patients (74.47%, 2.33–4.80 log10 copies/ml). These levels correlated not only with the intrahepatic HBV-RNA level and the ratio of intrahepatic HBV-RNA to covalently closed circular DNA (cccDNA), but also with the histological scores for grading and staging. Regarding quasispecies, serum HBV-RNA was dynamic and more genetically homogenous to simultaneously sampled intrahepatic HBV-RNA than to the cccDNA pool. In situ histology revealed that HBV-RNA–positive hepatocytes were clustered in foci, sporadically distributed across the lobules, and co-localized with hepatitis B surface antigen.
ConclusionSerum HBV-RNA levels reflect intrahepatic viral transcriptional activity and are associated with liver histopathology in patients receiving NUC therapy. Our study sheds light on the nature of HBV-RNA in the pathogenesis of chronic HBV infection and has implications for the management of chronic hepatitis B during NUC therapy.
Lay summarySerum HBV-RNA levels are indicative of the intrahepatic transcriptional activity of covalently closed circular DNA and are associated with liver histological changes in patients with chronic B hepatitis who are receiving nucleos(t)ide analogue therapy.
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发表于 2017-12-20 08:37