Details

Autor(en) / Beteiligte

• Wang, Jing
• Yu, Yiqi
• Li, Guojun
• Shen, Chuan
• Meng, Zhefeng
• Zheng, Jianming
• Jia, Yanhong
• Chen, Shaolong
• Zhang, Xiao
• Zhu, Mengqi
• Zheng, Jiangjiang
• Song, Zhangzhang
• Wu, Jing
• Shao, Lingyun
• Qian, Peiyu
• Mao, Xiaona
• Wang, Xuanyi
• Huang, Yuxian
• Zhao, Caiyan
• Zhang, Jiming
• Qiu, Chao
• Zhang, Wenhong

Titel

Relationship between serum HBV-RNA levels and intrahepatic viral as well as histologic activity markers in entecavir-treated patients

Ist Teil von

• Journal of hepatology, 2018-01, Vol.68 (1), p.16-24

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2018

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• [Display omitted] •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. In 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. A 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. Serum HBV-RNA was detected in 35 of 47 patients (74.47%, 2.33–4.80log10copies/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. Serum 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. Serum 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.