Methodology-dependent performance of serum HBV RNA in predicting treatment outcomes in chronic hepatitis B patients

Shi, Liu; Wu, Yaobo; Deng, Rui; shen, Sheng; Fan, Rong; Peng, Jie; Li, Wanying; Liang, Xieer; Hou, Jinlin; Sun, Jian; Zhou, Bin

doi:10.1016/j.antiviral.2021.105037

Cited by 12 publications

(10 citation statements)

References 28 publications

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“…Currently, there are various methods to detect serum pgRNA determined by targets used by the assays. Shi Liu et al 18 reported that methodologies targeting both the 5′and 3′ends of the HBV pgRNA, the S region, and the Xregion had similar performance in predicting clinical relapse and HBeAg loss. Targeting polyA tail of HBV RNA was not satisfactory.…”

Section: Discussionmentioning

confidence: 99%

Reduction in Intrahepatic cccDNA and Integration of HBV in Chronic Hepatitis B Patients with a Functional Cure

Wei¹,

Gao²,

Gu³

et al. 2022

J Clin Transl Hepatol

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Background and Aims: Functional cure (FC) is characterized by the clearance of the hepatitis B surface antigen from the serum of patients with chronic hepatitis B (CHB). However, the level of intrahepatic covalently closed circular DNA (cccDNA) and hepatitis B virus (HBV) integration remains unclear. We conducted this study to determine them and reveal their value in the treatment of CHB. Methods: There were two sessions to elucidate the changes in intrahepatic cccDNA and HBV integration after antiviral therapy. In the first session, 116 patients were enrolled and divided into FC, non-functional cure (NFC), and CHB groups, including 48 patients with functionally cured CHB, 27 with CHB without functional cure after antiviral treatment, and 41 with treatment-naïve CHB. Patients were tested for both intrahepatic cccDNA and other viral markers. All patients in the FC group were followed up for at least 24 weeks to observe relapse. In the second session, another ten patients were included for in-depth whole-genome sequencing to analyze HBV integration. Results: Thirteen patients in the FC group were negative for intrahepatic cccDNA. Intrahepatic cccDNA was much higher in the CHB group compared with the FC group. Seven patients had HBsAg seroreversion, including two with virological relapse. Integration of HBV was detected in one (33.3%) functionally cured patients and in seven (100%) with CHB. 28.0% of the HBV breakpoints were assigned in the 1,500 nt to 1,900 nt range of the HBV genome. Conclusions: After achieving an FC, the rate of intrahepatic

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Section: Discussionmentioning

confidence: 99%

Reduction in Intrahepatic cccDNA and Integration of HBV in Chronic Hepatitis B Patients with a Functional Cure

Wei¹,

Gao²,

Gu³

et al. 2022

J Clin Transl Hepatol

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“…As a surrogate biomarker for intrahepatic cccDNA quantity and transcript activity, serum HBV RNA level has been con rmed to be a valuable marker for CHB management, including natural course management and antiviral management [10-16, 18-20, 24-27]. [30] but also different in treatment outcomes [31]. Therefore, before serum RNA is applied to clinical practice in the future, further understanding of the biological signi cance of serum HBV pgRNA and standardization of testing methods is critical.…”

Section: Discussionmentioning

confidence: 99%

Early Serum HBV RNA Level in Combination With the HBeAg Response Can Effectively Predict the HBeAg Response in Patients on Nucleos(t)ide Analogue Therapy (ClinicalTrials.gov (NCT03909191)

Liu

Liao

et al. 2021

Preprint

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Background: Serum HBV RNA level has the potential to monitor antiviral therapy in patients with chronic hepatitis B. This study aimed to explore serum HBV RNA dynamic change pattern and its predict value on the efficacy of 96 weeks nucleos(t)ide analogue (NA) treatment in HBeAg-positive and HBeAg-negative patients with chronic hepatitis B (CHB).Methods: A real-life cohort study of 78 patients with CHB on NA treatment was conducted. Dynamic change patterns of serum HBV RNA and correlation with other HBV markers in the early treatment period of 96 weeks of NA treatment in patients with CHB were determined and compared. The performance of serum HBV RNA on treatment efficacy was analyzed by receiver operating characteristic (ROC) analyses. Results: HBeAg-positive and HBeAg-negative patients with CHB had similar viral change patterns during NA treatment. Serum HBV RNA level was consistently correlated with HBeAg and HBsAg titers in HBeAg-positive patients during NA treatment, but serum HBV RNA was only moderately correlated with serum HBV DNA level in HbeAg-negative patients before treatment. Serum HBV RNA decreased more rapidly in patients with the HBeAg seroconversion (SC) response than in patients without the HBeAg SC response; it had good early discriminatory ability for the HBeAg response with area under the ROC curve (AUROC) of 0.70 and 0.730 at 12 and 24 weeks of treatment, respectively. The cutoff value of serum HBV RNA of 4.31 log cps/mL in combination with the HBeAg decrease degree of 1.55 at 24 weeks of treatment had a good two-way predictive capability for the HBeAg response (PPV%: 83.33% and NPV%: 81.25%), and the specificity was 96.30%. Conclusion: Serum HBV RNA level had early discriminatory ability for the HBeAg response. Early HBeAg response can improve the discriminatory ability of serum HBV RNA.

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“…The wtRNA quantification assay has been previously reported in our publications. [13][14][15][16] The positions of the primers designed to detect spRNAs are shown in Supporting Information S1: Figure 2. The RT-qPCR system for specifically quantifying spRNA was optimized, rendering it incapable of quantifying HBV wtRNA (Supporting Information S1: Table 2).…”

Section: Quantification Of Serum Hbv-spliced and Wtrnasmentioning

confidence: 99%

Serum hepatitis B virus spliced RNA proportion increases with liver disease progression in patients with chronic hepatitis B

Lu,

Li,

Deng

et al. 2024

Journal of Medical Virology

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Serum hepatitis B virus (HBV) spliced RNAs (spRNAs) are ubiquitous in HBV‐infected patients; however, their clinical significance remains unknown. Therefore, we aimed to explore the relationship between HBV spRNAs and liver disease progression in chronic hepatitis B (CHB) patients; in vitro cell line assessment was also performed. The serum HBV wild‐type RNA (wtRNA) and spRNA levels were individually quantified in a cohort of 279 treatment‐naïve, hepatitis B e antigen positive CHB patients with or without cirrhosis. The spRNA proportion was determined as (spRNA × 100%)/(spRNAs + wtRNA). 20 patients' serum samples underwent spRNA species profiling using next‐generation sequencing. Serum spRNA species 1, 2, 3, 4, and 5 were the most common variants. The spRNA proportion varied from 0.00% to 19.02%, with higher levels in HBV genotype C patients than in those with genotype B (1.76% vs. 0.84%, p < 0.001). The spRNA proportion was positively associated with the alanine aminotransferase levels (r = 0.144, p = 0.053) and significantly higher in cirrhotic than in non‐cirrhotic patients (1.69% vs. 1.04%, p = 0.001). Multivariate analysis revealed a 2.566‐fold higher risk of cirrhosis in patients with elevated spRNA proportion (p = 0.024). In vitro experiments confirmed that spRNAs contributed to hepatic stellate cell activation, which is critical in liver fibrosis development. Therefore, increased HBV spRNA expression poses a risk for liver disease progression. Quantifying serum HBV spRNAs can aid in monitoring liver disease progression. Furthermore, the therapeutic targeting of spRNAs may improve the prognosis of patients with CHB.

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Methodology-dependent performance of serum HBV RNA in predicting treatment outcomes in chronic hepatitis B patients

Cited by 12 publications

References 28 publications

Reduction in Intrahepatic cccDNA and Integration of HBV in Chronic Hepatitis B Patients with a Functional Cure

Reduction in Intrahepatic cccDNA and Integration of HBV in Chronic Hepatitis B Patients with a Functional Cure

Early Serum HBV RNA Level in Combination With the HBeAg Response Can Effectively Predict the HBeAg Response in Patients on Nucleos(t)ide Analogue Therapy (ClinicalTrials.gov (NCT03909191)

Serum hepatitis B virus spliced RNA proportion increases with liver disease progression in patients with chronic hepatitis B

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