Monitoring the emergence of HBV resistance mutations by HBV-RNA pyrosequencing

Bottecchia, Marcelle; Barcaiu, Halime Silva; Lewis-Ximenez, Lia Laura; Mouta, Sergio da Silva e; Moraes, Marcia Terezinha Baroni de

doi:10.1016/j.bjid.2015.11.004

Cited by 6 publications

(7 citation statements)

References 5 publications

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“…Second, rather than being produced by a viral integrant, serum HBV‐RNA is produced by cccDNA, reflecting cccDNA‐directed viral transcriptional activity, which is required for viral replication . Third, serum HBV‐RNA is more valuable for monitoring drug resistance when serum HBV‐DNA is effectively suppressed . Fourth, sustained undetectable levels of serum HBV‐RNA could be used as an additional endpoint of treatment for defining virological response if a threshold can be determined below which the host is likely to control or inactivate cccDNA‐directed transcriptional activity …”

Section: Discussionmentioning

confidence: 99%

“…31 Third, serum HBV-RNA is more valuable for monitoring drug resistance when serum HBV-DNA is effectively suppressed. 21,22 Fourth, sustained undetectable levels of serum HBV-RNA could be used as an additional endpoint of treatment for defining virological response if a threshold can be determined below which the host is likely to control or inactivate cccDNA-directed transcriptional activity. 12 Our findings also provide clues for further investigation into the mechanisms underlying regulation of viral replication during different phases of CHB.…”

Section: Discussionmentioning

confidence: 99%

“…Serum HBV‐RNA levels have also been implemented in clinical studies for potential use in predicting response to treatment, guiding discontinuation of nucleot(s)ide analog therapy, and monitoring the emergence of viral mutation during antiviral treatment . Sustained undetectable levels of serum HBV‐RNA, indicating low levels of cccDNA‐directed transcriptional activity in the liver, might be a realistic endpoint of treatment for defining the virological response .…”

Section: Introductionmentioning

confidence: 99%

“…17 Serum HBV-RNA levels have also been implemented in clinical studies for potential use in predicting response to treatment, 14,15,[18][19][20] guiding discontinuation of nucleot(s)ide analog therapy, 12 and monitoring the emergence of viral mutation during antiviral treatment. 21,22 Sustained undetectable levels of serum HBV-RNA, indicating low levels of cccDNA-directed transcriptional activity in the liver, might be a realistic endpoint of treatment for defining the virological response. 12,13,23 Hence, monitoring serum HBV-RNA levels may be useful for the management of CHB, aiding in decisions regarding the initiation of therapy, switching of treatment regimens and cessation of treatment for individuals during clinical practice.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Natural history of serum HBV‐RNA in chronic HBV infection

Wang

et al. 2018

Journal of Viral Hepatitis

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“…It was firstly shown that, in patients receiving lamivudine therapy, HBV RNA becomes detectable in serum during treatment and that is inhibited by interferon-alpha (IFN-α) [ 59 , 101 ]. It has also been postulated that serum HBV RNA might be a predictor of early emergence of viral resistance mutations during NA therapy [ 55 , 102 ]. In one fairly recent study that included 12 HBeAg(-) NA treated patients, a positive correlation between the levels of serum HBV RNA and HBV DNA as well as with qHBsAg was demonstrated and the HBV RNA kinetics of HBeAg(-) and HBeAg(+) patients who achieved seroconversion were found to be similar [ 65 ].…”

Section: Clinical Significance Of Viral Biomarkers In Hbeag(-) Infmentioning

confidence: 99%

Viral Biomarkers in Chronic HBeAg Negative HBV Infection

Hadziyannis

Laras

2018

Genes

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Viral biomarkers are important tools for monitoring chronic hepatitis B virus (HBV) hepatitis B early antigen (HBeAg) negative infection, both in its natural course as well as during and after treatment. The biomarkers consist of antibodies against viral epitopes, viral proteins, and molecular surrogate markers of the quantity and transcriptional activity of the stable episomal HBV covalently closed circular DNA (cccDNA) which is located in the nuclei of the infected hepatocytes. HBV deoxyribonucleic acid (DNA) or else viral load measurement in plasma or serum is a marker of HBV replication of major clinical importance. HBV DNA is used for staging and treatment monitoring as described in international scientific guidelines. Quantification of HBV antigens, mainly hepatitis B surface antigen (HBsAg) as well as Hepatitis B core related antigen (HBcrAg), play an important yet secondary role, especially in cases of low or undetectable HBV DNA and has been evaluated for the classification of the inactive carrier state, as a predictor of subsequent HBsAg clearance, treatment outcome, and development of hepatocellular carcinoma (HCC). The measurement of the replicative intermediate HBV RNA in serum is currently evaluated and may also prove to be a significant biomarker particularly in patients treated with nucleot(s)ide analogs. This review focuses on the viral biomarkers mentioned above and their role in HBV, HBeAg negative, infection.

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Nucleos(t)ide analogues altered quasispecies composition of hepatitis B virus (HBV)‐resistant mutations in serum HBV DNA and serum HBV RNA

Liao

Zhang

Shao

et al. 2023

Journal of Medical Virology

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Serum hepatitis B virus (HBV) RNA is a new serological indicator reflecting viral replication with good clinical application prospects. This study aimed to clarify the dynamic changes of serum HBV RNA levels and the quasispecies of HBV RNA viruslike particles in nucleos(t)ide analogues (NAs)-experienced chronic hepatitis B (CHB) patients harboring NAs-resistant mutations and their identifiable effects on NAs resistance. We included CHB patients who were on long-term NAs treatment and with HBV DNA rebound. The longitudinally dynamics of serum HBV RNA levels were quantitatively detected, and the quasispecies differences between serum HBV DNA and serum HBV RNA were compared by high-throughput sequencing. The effect of NAs concentration pressure on altering the resistance mutations quasispecies proportion of HBV DNA and HBV RNA in cell supernatant was analyzed in vitro. A total of 447 serum samples from 36 CHB patients treated with NAs were collected. The median follow-up period was 47 months (about 4 years), and the longest follow-up period was 117 months (about 10 years). Our results showed that HBV RNA could reflect virological breakthrough in 23 (64%, 23/36) patients, and serum HBV RNA rebound earlier than HBV DNA in 12 (52%, 12/23) patients. However, serum HBV RNA remained at a consistently high level and did not fluctuate significantly with the HBV DNA rebound in 6 of 36 patients.

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Monitoring the emergence of HBV resistance mutations by HBV-RNA pyrosequencing

Cited by 6 publications

References 5 publications

Natural history of serum HBV‐RNA in chronic HBV infection

Natural history of serum HBV‐RNA in chronic HBV infection

Viral Biomarkers in Chronic HBeAg Negative HBV Infection

Nucleos(t)ide analogues altered quasispecies composition of hepatitis B virus (HBV)‐resistant mutations in serum HBV DNA and serum HBV RNA

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