Composition and Interactions of Hepatitis B Virus Quasispecies Defined the Virological Response During Telbivudine Therapy

Zhou, Bin; Dong, Hui; He, Yungang; Sun, Jian; Jin, Weihua; Xie, Qing; Fan, Rong; Wang, Minxian; Li, Ran; Chen, Yangyi; Xie, Shaoqing; Shen, Yan; Huang, Xin; Wang, Shengyue; L, Feng-ming; Jia, Jidong; Zhang, Hui; Locarnini, Stephen; Zhao, Guoping; Jin, Li; Hou, Jinlin

doi:10.1038/srep17123

Cited by 13 publications

(16 citation statements)

References 33 publications

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“…For example, a minor variant that confers drug resistance in HIV that is present in only 2.1% of sequencing reads in a patient at baseline can rapidly become the majority (consensus) variant under the selective pressure of drug treatment 46 . Similar changes in the frequency of resistance-associated alleles during treatment have been observed for HBV 47 , HCV 48 , HCMV 12 and influenza virus 49 .…”

Section: Practical Considerationssupporting

confidence: 70%

Clinical and biological insights from viral genome sequencing

2017

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| Whole-genome sequencing (WGS) of pathogens is becoming increasinglyimportant not only for basic research but also for clinical science and practice. In virology, WGS will be important for the development of novel treatments and vaccines and for increasing the power of molecular epidemiology and evolutionary genomics. In this Opinion article, we suggest that WGS of viruses in a clinical setting will become increasingly important for patient care. We give an overview of different WGS methods used in virology and summarize their advantages and disadvantages. Although there are only partially addressed technical, financial and ethical issues with the clinical application of viral WGS, this technique

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Section: Practical Considerationssupporting

confidence: 70%

Clinical and biological insights from viral genome sequencing

2017

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“…12, 13, 24, 25, 26 However, the characteristics of the entire genomes of HBV quasispecies determined using ultra-deep sequencing during G145R mutant infection have not yet been reported. The quasispecies heterogeneity within the S and RT regions had not changed significantly during the 4th week compared with baseline but clearly increased 1 month after the onset of administration of entecavir.…”

Section: Discussionmentioning

confidence: 99%

Clinical features and viral quasispecies characteristics associated with infection by the hepatitis B virus G145R immune escape mutant

Xue

Wang

Yang

et al. 2017

Emerging Microbes & Infections

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Coexistence of the hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) is an uncommon phenomenon, and the underlying mechanisms remain largely unknown. Amino-acid (aa) substitution from glycine to arginine at aa 145 (G145R), in the major hydrophilic region, has been reported in patients with HBsAg and anti-HBs coexistence. However, there is limited knowledge about the clinical features and viral quasispecies characteristics associated with G145R mutant hepatitis B virus (HBV) infection. We herein describe the dynamic changes in the serological and virological markers in a case of hepatitis B with coexisting HBsAg and anti-HBs, caused by a G145R immune escape mutant (genotype C). Entecavir was administered during the 4th week after admission. Alanine aminotransferase peaked in the 16th week, while both the HBsAg and HBeAg declined rapidly. HBsAg clearance and hepatitis B e antigen (HBeAg)/hepatitis B e antibody (anti-HBe) seroconversion were achieved in the 36th week, and then entecavir was withdrawn. A follow-up of 96 weeks showed that HBV DNA remained undetectable and that anti-HBs was maintained above 100 mIU/mL. The quasispecies characteristics of the G145R mutant HBV were investigated via ultra-deep sequencing. The complexity and genetic distance of the S and RT regions were much higher in the 8th week than at baseline or in the 4th week. Moreover, the frequencies of mutations (L173P, Q181R and A184V) in cytotoxic T lymphocyte epitopes increased before entecavir treatment. These findings extend understanding of the evolution of HBV under host immune pressure and of the clinical outcomes of affected patients.

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“…In the present study, clinical and laboratory assessments were made every 12 weeks or 16 weeks during NAs treatment. HBV DNA and HBV serological markers were measured with the platform of Roche COBAS TaqMan™ HBV Test v1.0 (before April 2014, with a lower limit of detection [LLoD] of 12 IU/mL) or v2.0 (after April 2014, with a LLoD of 20 IU/mL) and ARCHITECT i2000SR at the central laboratory set up by the research group 27 . Undetectable HBV DNA was defined as serum HBV DNA below the LLoD during NAs treatment 4 .…”

Section: Methodsmentioning

confidence: 99%

Factors associated with the biphasic kinetics of serum HBV RNA in patients with HBeAg‐positive chronic hepatitis B treated with nucleos(t)ide analogues

Shi

Liu

et al. 2020

Aliment Pharmacol Ther

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Summary Background Serum hepatitis B virus (HBV) RNA is a novel biomarker for evaluating treatment response. Detailed information regarding serum HBV RNA kinetics during treatment with nucleos(t)ide analogues (NAs) is limited. Aims To ascertain serum HBV RNA kinetics during long‐term NA treatment and identify associated factors. Methods We enrolled 76 HBeAg‐positive chronic hepatitis B patients receiving NA from randomised controlled trials. Laboratory assays were undertaken every 3 months. Factors associated with serum HBV RNA kinetics were identified by generalised estimating equations. Results Baseline serum HBV RNA was 8.5 ± 1.0 log10 copies/mL. Decline in serum HBV RNA during NA therapy was biphasic: the first phase (HBV DNA detectable) had a fast decrease (median slope, −0.207 log10 copies/mL/month) and was followed by a second phase (HBV DNA undetectable) with slow decrease (median slope, −0.071 log10 copies/mL/month). In the first phase, factors independently associated with lower initial serum HBV RNA were male sex (OR, 0.685, P = 0.044), low baseline HBsAg (OR, 0.525, P = 0.001) and rapid virological response (RVR) (OR, 0.624, P = 0.031). In the second phase, only RVR was independently associated with serum HBV RNA kinetics, including its lower initial level (OR, 0.694, P = 0.043) and greater decline (OR, 0.966, P = 0.002). Based on viral dynamics, time needed to achieve undetectable serum HBV RNA from baseline was 43.56 (IQR: 29.49‐66.40) months. Conclusion RVR was a significant determinant for biphasic decline in serum HBV RNA during NA treatment, which significantly influenced the treatment duration required to achieve undetectable serum HBV RNA.

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Composition and Interactions of Hepatitis B Virus Quasispecies Defined the Virological Response During Telbivudine Therapy

Cited by 13 publications

References 33 publications

Clinical and biological insights from viral genome sequencing

Clinical and biological insights from viral genome sequencing

Clinical features and viral quasispecies characteristics associated with infection by the hepatitis B virus G145R immune escape mutant

Factors associated with the biphasic kinetics of serum HBV RNA in patients with HBeAg‐positive chronic hepatitis B treated with nucleos(t)ide analogues

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