Serum HBV DNA plus RNA shows superiority in reflecting the activity of intrahepatic cccDNA in treatment-naïve HBV-infected individuals

Huang, Hongxin; Wang, Jie; Li, Weijie; Chen, Ran; Chen, Xiangmei; Zhang, Fengmin; Xu, Da; Lu, Fengmin

doi:10.1016/j.jcv.2017.12.016

Cited by 73 publications

(101 citation statements)

References 45 publications

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“…Though the weak correlation of serum HBV RNA with both serum HBcrAg and HBsAg indicated a different possibility for its applicability in future, serum HBV RNA should be at least not an ideal indicator for the activity of HBV replication in liver tissue. In fact, the poor efficacy of serum HBV RNA in reflecting intrahepatic cccDNA activity was also reported in another recently published study …”

Section: Discussioncontrasting

confidence: 69%

“…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). Undetectable serum HBV RNA level has been reported to be associated with sustained virological response to antiviral therapy, and it might serve as a new potential surrogate marker to reflect the status of intrahepatic cccDNA . In addition, some scholars have called for a new definition of sustained virological response (using undetectable HBV DNA plus HBV RNA in place of undetectable HBV DNA) .…”

Section: Introductionmentioning

confidence: 99%

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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%

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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“…The RACE–quantitative PCR–based flRNA quantification has been widely employed in recent studies . In addition to RACE–quantitative PCR, regular quantitative RT‐PCR methods with HBV‐specific primers targeting the X, C, or S region of the HBV genome were developed to quantify serum HBV RNA . However, in order to avoid DNA contamination during quantitative RT‐PCR, deoxyribonuclease I treatment of the nucleic acids extracted from serum is required.…”

Section: Serum Hbv Rna Species and Measurementmentioning

confidence: 99%

“…Consistently, van Bommel et al have demonstrated that the levels of both serum HBV flRNA and trRNA strongly correlate with serum HBV DNA before treatment, but the correlation becomes weaker upon receiving NAs (Table ). For untreated patients, the correlation coefficient of serum HBV pgRNA and DNA is higher in hepatitis B e antigen (HBeAg)–negative patients than HBeAg‐positive patients ( r = 0.741 and r = 0.532, P < 0.001, respectively) . However, van Campenhout et al reported a comparable correlation of serum HBV flRNA to DNA between HBeAg‐positive and HBeAg‐negative patients ( r = 0.72 and r = 0.78, P < 0.001, respectively) .…”

Section: Correlation Between Serum Hbv Rna and Other Hbv Markersmentioning

confidence: 99%

Serum Hepatitis B Virus RNA: A New Potential Biomarker for Chronic Hepatitis B Virus Infection

et al. 2019

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Chronic hepatitis B infection is one of the major etiological causes of liver failure, cirrhosis, and hepatocellular carcinoma (HCC) worldwide. This condition cannot be completely cured by currently available drugs due to the persistent existence of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), the bona fide transcription template for HBV RNAs, in infected hepatocytes. Because quantifying cccDNA per se requires an invasive procedure, serum biomarkers reflecting intrahepatic cccDNA activity are warranted. Recently, a growing body of research suggests that the circulating HBV RNA may serve as a serum biomarker for HBV infection, treatment, and prognosis. In order to delineate the molecular and clinical characteristics of serum HBV RNA, we systematically reviewed the available literature on serum HBV RNA dating back to the early 1990s. In this review, we summarize the reported serum HBV RNA quantification methods and discuss the potential HBV RNA species in patient serum. We also compare the reported correlations of serum HBV RNA with other serological markers, including HBV DNA, hepatitis B surface antigen, e antigen, and core‐related antigen, as well as their correlations with intrahepatic cccDNA, to assess their potential in clinical applications. Future directions for serum HBV RNA research are also discussed.

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“…In this study, the S gene mutation was found in a patient with HBV DNA reappearance and HBV DNA level high enough for the PCR‐based sequence analysis. Furthermore, the positive serum HBV RNA with negative HBV DNA indicated that intrahepatic cccDNA might be in a transcriptional active state, but with the decreased reverse transcriptional activity of HBV DNA polymerase (p‐protein) mediated by either NAs treatment and/or the P gene mutation . Accordingly, for the diagnosis of occult HBV infection (OBI), we suggest that the persistence of HBV RNA should also be taken into consideration.…”

Section: Discussionmentioning

confidence: 99%

Serum HBV RNA is a Potential Predictor of Hepatitis B Surface Antigen Reversion

Wang

Chen

et al. 2018

Hepatology Communications

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Serum HBV DNA plus RNA shows superiority in reflecting the activity of intrahepatic cccDNA in treatment-naïve HBV-infected individuals

Cited by 73 publications

References 45 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

Serum Hepatitis B Virus RNA: A New Potential Biomarker for Chronic Hepatitis B Virus Infection

Serum HBV RNA is a Potential Predictor of Hepatitis B Surface Antigen Reversion

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