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

Wang, Jing; Yu, Yiqi; Li, Guojun; Shen, Chuan; Meng, Zhi Qiang; Zheng, Jianming; Jia, Yanhong; Chen, Shao-Long; Xiao, Zhijian; Zhu, Mengqi; Jun, Zheng; Song, Zhangzhang; Wu, Jing; Shao, Lingyun; Qian, Peng; Mao, Xiaona; Wang, Xuanyi; Huang, Yuxian; Zhao, Caiyan; Zhang, Jiming; Qiu, Chao; Zhang, Wenhong

doi:10.1016/j.jhep.2017.08.021

Cited by 107 publications

(173 citation statements)

References 29 publications

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“…In the present study, the levels of serum HBV RNA were similar between patients with different inflammation grade and fibrosis stage. However, Prof. Zhang WH and his team reported an association between serum HBV RNA levels and liver histological changes ( r = 0.665 for grading and r = 0.722 for staging) in patients receiving NAs therapy . Due to the fact that there were limited studies and small samples were provided, more data are still required to clarify whether the level of serum HBV RNA could effectively predict severe inflammation and advanced fibrosis.…”

Section: Discussioncontrasting

confidence: 69%

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Serum HBcrAg is better than HBV RNA and HBsAg in reflecting intrahepatic covalently closed circular DNA

Chen

Wang

Tao

et al. 2019

Journal of Viral Hepatitis

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Summary The correlation between serum HBcrAg and HBV RNA is unclear, and correlations of intrahepatic cccDNA with HBcrAg, HBV RNA and HBsAg are rarely reported in the same cohort. This study aimed to assess the correlation of HBcrAg with HBV RNA and HBsAg, and investigate whether serum HBcrAg is superior to serum HBV RNA and HBsAg in reflecting intrahepatic HBV cccDNA in HBeAg‐positive and HBeAg‐negative CHB patients. In this study, 85 HBeAg‐positive and 25 HBeAg‐negative patients who have never received antiviral therapy were included. Among HBeAg‐positive patients, HBcrAg was correlated positively with HBsAg (r = 0.564, P < 0.001) and HBV RNA (r = 0.445, P < 0.001), and HBV RNA was also correlated positively with HBsAg (r = 0.323, P = 0.003). Among HBeAg‐negative patients, no significant correlation was observed between HBcrAg, HBsAg and HBV RNA. By multivariable linear regression, HBcrAg (β = −0.563, P < 0.001), HBsAg (β = −0.328, P < 0.001) and HBV RNA (β = 0.180, P = 0.003) were all associated with cccDNA levels among HBeAg‐positive patients, but only serum HBcrAg was associated with cccDNA level (β = 0.774, P = 0.000) among HBeAg‐negative patients. HBcrAg was better correlated with cccDNA as compared to HBsAg and HBV RNA, irrespective of HBeAg status. Among HBeAg‐positive patients, though HBcrAg level was influenced by hepatic inflammatory activity and HBV DNA levels, the good correlations of HBcrAg with cccDNA persisted after stratification by inflammatory activity and HBV DNA levels. In conclusion, correlations of serum HBcrAg, HBV RNA and HBsAg levels differ significantly between HBeAg‐positive and HBeAg‐negative patients, but serum HbcrAg correlates with cccDNA levels better than HBV RNA and HBsAg, irrespective of HBeAg status.

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Section: Discussioncontrasting

confidence: 69%

“…Recently, serum HBV RNA is also attracting attention as a useful biomarker . As early as 1996, serum HBV RNA was identified in HBV‐infected patients but its nature and origin were unclear until recently when serum HBV RNA was confirmed to be pregenomic RNA (pgRNA).…”

Section: Introductionmentioning

confidence: 99%

Serum HBcrAg is better than HBV RNA and HBsAg in reflecting intrahepatic covalently closed circular DNA

Chen

Wang

Tao

et al. 2019

Journal of Viral Hepatitis

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“…Halgand et al, showed a correlation between the detection of pgRNA and cccDNA in tumors, and the absence of tumorous microvascular invasion and better patient survival (24). Wang et al, revealed that the serum HBV RNA level is in correlation with the intrahepatic HBV RNA level, intrahepatic HBV RNA, cccDNA, and the histological scores for grading and staging (25). The current study also found that the pretreatment intrahepatic cccDNA was positively correlated with serum HBV RNA (r = 0.25, P = 0.02) (16).…”

supporting

confidence: 71%

Characterization of Serum HBV RNA in Patients with Untreated HBeAg-Positive and -Negative Chronic Hepatitis B Infection

et al. 2018

Hepat Mon

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Background: The serum hepatitis B virus (HBV) RNA is suggested as a potential new biomarker of HBV infection. However, it is not fully understood. Objectives: The current study aimed at characterizing serum HBV RNA in patients with untreated chronic hepatitis B (CHB) and genotype B and C HBV infection. Methods: A large cohort of 483 patients with hepatitis B e antigen (HBeAg)-positive and -negative was performed. The routine serum biomarkers of HBV infection were tested. HBV genotyping was carried out by direct sequencing. Serum HBV RNA levels were quantified using a method described in the authors' previous study (lower limit of detection: 66.7 IU/mL). Results: Serum HBV RNA was detected in 92.5% (394/426) of the patients with HBeAg-positive and 31.6% (18/57) of HBeAg-negative ones; a positive association was observed between HBeAg and HBV RNA statuses in the subjects. Alanine aminotransferase (ALT), HBV DNA, and genotype were the independent predictors in patients with HBeAg-positive CHB (P = 0.024, 0.001 and 0.014, respectively), while it was HBV DNA in the negative ones (P = 0.000) for serum HBV RNA detectability. Serum HBV RNA was positively correlated with ALT, aspartate transaminase (AST) and HBV DNA, regardless of HBeAg status, and with hepatitis B surface antigen (HBsAg) in HBeAg-positive ones (P < 0.05). Conclusions: Serum HBV RNA may be affected by HBeAg status, serum HBV DNA, HBsAg levels, HBV genotype, ALT, and AST levels. There might be some similarities between the characteristics of serum HBV RNA, and serum HBV DNA and HBsAg, regardless of its distinctive features. The roles of serum HBV RNA in viral replication, infection, survival, disease progression, and antiviral responses need to be investigated in further studied.

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“…Primer sequences and protocols for each target used in the study are listed in Figure and Table . The primers HBV cccDNA‐FW and HBV cccDNA‐RV were the same as those used in previous studies by ourselves and other groups . HBV viral load was quantified using COBAS AmpliPrep and COBAS TaqMan Kits (Roche Diagnostics, Mannheim, Germany) with a detection limit of 20 IU mL −1 (100 copies mL −1 ).…”

Section: Methodsmentioning

confidence: 99%

Natural history of serum HBV‐RNA in chronic HBV infection

Wang

et al. 2018

Journal of Viral Hepatitis

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Virus-like particles encapsulating HBV-RNA represent a serum biomarker for assessing viral replication activity in clinical practice. However, baseline levels of serum HBV-RNA and their associations with viral replicative intermediates and liver disease in phases of chronic hepatitis B remain unknown. In this cross-sectional study, 102 patients were categorized into immune-tolerant (IT), HBeAg-positive immune active (HBeAg+IA), inactive carrier (IC) and HBeAg-negative immune active (HBeAg-IA) phases. HBV-RNA in serum samples and in 66 paired liver biopsies were quantified and correlated with serum ALT levels, histopathological scores and the levels of other viral replicative intermediates. Mean levels of serum HBV-RNA differed among phases, with the highest levels among IT (6.78 ± 0.83 log copies mL ) patients, followed by HBeAg+IA (5.73 ± 1.16 log copies mL ), HBeAg-IA (4.52 ± 1.25 log copies mL ) and IC (2.96 ± 0.40 log copies mL ) patients. Serum HBV-RNA levels correlated with HBV DNA in all phases, although correlations with other viral replicative intermediates weakened or disappeared when cases were stratified into phases. Distinct compositions of viral products were found among phases: the ratio of HBsAg to serum HBV-RNA was highest in IC patients, while the ratio of serum HBV-RNA to intrahepatic HBV-RNA and the ratio of intrahepatic HBV-DNA to intrahepatic HBV-RNA were significantly higher in IT patients. In conclusion, baseline levels of HBV-RNA and the composition of viral replicative intermediates differ significantly across the natural course of chronic HBV infection. These findings shed light on the nature of viral replication and pathogenesis of disease among different phases of chronic HBV infection.

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

Cited by 107 publications

References 29 publications

Serum HBcrAg is better than HBV RNA and HBsAg in reflecting intrahepatic covalently closed circular DNA

Serum HBcrAg is better than HBV RNA and HBsAg in reflecting intrahepatic covalently closed circular DNA

Characterization of Serum HBV RNA in Patients with Untreated HBeAg-Positive and -Negative Chronic Hepatitis B Infection

Natural history of serum HBV‐RNA in chronic HBV infection

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