Serum hepatitis B virus RNA levels as an early predictor of hepatitis B envelope antigen seroconversion during treatment with polymerase inhibitors

Bömmel, Alena van; Bartens, Anne; Myšičková, Alena; Hofmann, Jörg; Krüger, Detlev H.; Edelmann, Anke

doi:10.1002/hep.27381

Cited by 208 publications

(262 citation statements)

References 21 publications

(68 reference statements)

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“…Mean HBV RNA level was 2.4 log 10 lower in HBeAg‐negative as compared to HBeAg‐positive patients, and the proportion of patients with undetectable HBV RNA serum level 23% in HBeAg‐negative as compared to only 0.5% in HBeAg‐positive patients ( P < 0.001). This is in line with previous findings in smaller patient cohorts 4, 7, 16. The correlation of HBV RNA with HBV‐DNA levels was similar in HBeAg‐positive and HBeAg‐negative individuals.…”

Section: Discussionsupporting

confidence: 94%

“…Quantification of polyadenylated HBV RNA was performed using specific primers (including HBV RNA RT primer 5′‐ACC ACG CTA TCG CTA CTC AC (dT17)GWA GCT C) designed according to van Bömmel et al7 For the current study the assay's lower limit of detection (LLD) for HBV RNA was 800 (2.9 log 10 ) copies/mL (c/mL), with a corresponding linear range of 800 to 10 6 c/mL. HBV RNA levels measured below the LLD were set to 450 c/mL before statistical analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Thus, before and during treatment with nucleos(t)ide analogue (NA) or pegylated interferon alfa (PEG‐IFN), a correlation between serum HBV RNA and the transcriptional activity of cccDNA was demonstrated 6. In addition, serum HBV RNA levels were found to be associated with the probability of response to treatment with either NAs or PEG‐IFN 2, 4, 7, 8, 9. However, before the further development of serum HBV RNA as a response‐predicting marker, it is mandatory to evaluate which factors which may influence HBV RNA levels in individuals who are eligible for treatment.…”

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confidence: 99%

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Host and viral factors associated with serum hepatitis B virus RNA levels among patients in need for treatment

et al. 2018

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Hepatitis B virus (HBV) RNA in serum is a novel biomarker for intrahepatic HBV replication and treatment response. For its proper use, it is essential to identify factors influencing serum HBV RNA level. Using a rapid amplification of complimentary DNA (cDNA) ends (RACE) PCR technique (lower limit of detection [LLD], 800 copies/mL [c/mL]), serum HBV RNA levels were measured in samples of 488 untreated individuals with chronic HBV infection who were eligible to treatment according to currently used recommendations. We explored the association of serum levels of HBV RNA with patient‐ and virus‐associated factors. HBV genotype distribution was 21/10/20/46/3% for A/B/C/D/other. Mean HBV RNA serum level was 5.9 (1.6) log10 c/mL (hepatitis B e antigen [HBeAg]‐positive chronic hepatitis B [CHB], 6.5 [1.2] log c/mL; HBeAg‐negative CHB, 4.1 [1.2] log c/mL; P < 0.001). By multivariable linear regression, factors associated with lower HBV RNA level were HBeAg negativity (β = –0.69; P < 0.001), HBV genotypes A (β = –0.13; P = 0.002), B (β = –0.07; P = 0.049), and C (β = –0.61; P < 0.001) in comparison to D, and presence of HBV basal core promoter mutation either alone (β = –0.14; P = 0.001) or in combination with precore mutation (β = –0.22; P < 0.001). Higher serum alanine aminotransferase (ALT) was associated with higher HBV RNA (β = 0.23; P < 0.001). HBV RNA correlated strongly with HBV DNA (HBeAg‐pos, r = 0.72; P < 0.001; HBeAg‐neg, r = 0.78; P < 0.001) and moderately with quantitative hepatitis B surface antigen (qHBsAg; HBeAg‐pos, r = 0.54; P < 0.001; HBeAg‐neg, r = 0.19; P = 0.04) and quantitative hepatitis B surface antigen (qHBeAg; r = 0.41; P < 0.001). Conclusion: In this multiethnic cohort of 488 untreated individuals with CHB, factors associated with serum HBV RNA level were HBeAg status, serum ALT, HBV genotype, and presence of basal core promotor mutations. For the future use of serum HBV RNA as a clinical marker, it seems mandatory to take these factors into consideration. (Hepatology 2018).

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Section: Discussionsupporting

confidence: 94%

Section: Methodsmentioning

confidence: 99%

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Host and viral factors associated with serum hepatitis B virus RNA levels among patients in need for treatment

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“…[236][237][238] A strong correlation between quantitative serum HBV RNA dynamics and HBeAg loss in both NA and PegIFNa treated patients 239 was recently demonstrated by using a new rapid amplification of cDNA-ends with polymerase chain reaction (RACE-PCR). 240 HBV RNA quantification might be also helpful in predicting viral rebound after discontinuation of NAs. 236 It should be further explored whether the simultaneous testing of different replicative, transcriptional and translational HBV biomarkers will allow for a better definition of the individual ''activity" of the chronic HBV infection helping to better predict long-term treatment outcomes.…”

Section: New Biomarkers Of Hbv Infectionmentioning

confidence: 99%

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

Lampertico¹,

Agarwal²,

Berg³

et al. 2017

Journal of Hepatology

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“…The serum HBV RNA are reported detectable in patients with chronic HBV infection (3,6,7) and its clinical significance are also suggested (8)(9)(10). It showed that serum HBV RNA dynamics had a strong correlation with HBeAg loss in patients treated with nucleoside-analogue or pegin-terferon (PegIFN)-α (9).…”

Section: Introductionmentioning

confidence: 97%

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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Serum hepatitis B virus RNA levels as an early predictor of hepatitis B envelope antigen seroconversion during treatment with polymerase inhibitors

Cited by 208 publications

References 21 publications

Host and viral factors associated with serum hepatitis B virus RNA levels among patients in need for treatment

Host and viral factors associated with serum hepatitis B virus RNA levels among patients in need for treatment

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

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

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