Review article: novel therapies for hepatitis B virus cure – advances and perspectives

Lin, Chun-Han; Kao, Jia‐Horng

doi:10.1111/apt.13694

Cited by 51 publications

(32 citation statements)

References 107 publications

(190 reference statements)

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“…This situation may be partly due to the presence of drug-resistant mutations of the virus and other factors such as intrinsic stability of the nuclear form of viral genome, the covalently closed circular DNA, and dysfunctional anti-HBV immune response of the host[11,15]. Our findings indicate that drug-resistant mutations of the virus are a minor but important reason for failure of virus eradication, a finding that is consistent with a previous report in which approximately 2% of nucleoside/nucleotide analogue-naïve Chinese patients with chronic hepatitis B had drug-resistant HBV[16].…”

Section: Discussionmentioning

confidence: 99%

“…Highly sensitive magnetic bead-based detection reagent was purchased from Hunan Shengxiang Biotechnology Co., Ltd (Northeast Gate, Hunan Province, China). The lower limit of detection with this reagent kit is 10 IU/mL, with comparable sensitivity and specificity to those with the COBAS TaqMan HBV assay for HBV DNA detection (Roche)[15,16]. A real-time PCR 7500 system was purchased from Applied Biosystems Inc. (Carlsbad, CA).…”

Section: Methodsmentioning

confidence: 99%

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Early hepatitis B viral DNA clearance predicts treatment response at week 96

Tan

Liu

et al. 2017

WJG

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AIMTo investigate whether hepatitis viral DNA load at 24 wk of treatment predicts response at 96 wk in patients with chronic hepatitis B.METHODSA total of 172 hepatitis B envelope antigen (HBeAg)-positive chronic hepatitis B patients who received initial treatment at 16 tertiary hospitals in Hunan Province, China were enrolled in this study. All patients received conventional doses of lamivudine and adefovir dipivoxil, telbivudine, entecavir dispersible tablets, or entecavir tablets for 96 wk. Patients who used other antiviral drugs or antitumor and immune regulation therapy were excluded. Patients were stratified into three groups according to their viral DNA load at 24 wk: < 10 IU/mL (group 1), 10-103 IU/mL (group 2), and > 103 IU/mL (group 3). Correlations of 24-wk DNA load with HBeAg negative status and HBeAg seroconversion at 96 wk were analyzed. Receiver operating characteristic curve analysis was used to test the predictive value of the HBV DNA load at 24 wk for long-term response.RESULTSThe rates of conversion to HBeAg negative status and HBeAg seroconversion rates were 53.7% and 51.9%, respectively, in group 1; 35.21% and 32.39% in group 2; and 6.38% and 6.38% in group 3. The receiver operating characteristic curves for the three subgroups revealed that the lowest DNA load (< 10 IU/mL) was better correlated with response at 96 wk than a higher DNA load (10-103 IU/mL). Nested PCR was used for amplifying and sequencing viral DNA in patients with a viral DNA load > 200 IU/mL at 96 wk; resistance mutations involving different loci were present in 26 patients, and three of these patients had a viral DNA load 10-103 IU/mL at 96 wk.CONCLUSIONHepatitis B viral DNA load at 24 wk of antiviral treatment in patients with chronic hepatitis B is a predictor of the viral load and response rate at 96 wk.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Early hepatitis B viral DNA clearance predicts treatment response at week 96

Tan

Liu

et al. 2017

WJG

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“…HTAs, which act by improving host immune ability, include therapeutic vaccines, immune checkpoint inhibitors, stimulators of exogenous interferon, and agents that induce APOBEC3A and APOBEC3B. These novel therapies are undergoing pre-clinical or clinical testing, and their effects should be further investigated [51,52]. …”

Section: Discussionmentioning

confidence: 99%

In Silico Analysis of Epitope-Based Vaccine Candidates against Hepatitis B Virus Polymerase Protein

Zheng

Lin

Wang

et al. 2017

Viruses

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Hepatitis B virus (HBV) infection has persisted as a major public health problem due to the lack of an effective treatment for those chronically infected. Therapeutic vaccination holds promise, and targeting HBV polymerase is pivotal for viral eradication. In this research, a computational approach was employed to predict suitable HBV polymerase targeting multi-peptides for vaccine candidate selection. We then performed in-depth computational analysis to evaluate the predicted epitopes’ immunogenicity, conservation, population coverage, and toxicity. Lastly, molecular docking and MHC-peptide complex stabilization assay were utilized to determine the binding energy and affinity of epitopes to the HLA-A0201 molecule. Criteria-based analysis provided four predicted epitopes, RVTGGVFLV, VSIPWTHKV, YMDDVVLGA and HLYSHPIIL. Assay results indicated the lowest binding energy and high affinity to the HLA-A0201 molecule for epitopes VSIPWTHKV and YMDDVVLGA and epitopes RVTGGVFLV and VSIPWTHKV, respectively. Regions 307 to 320 and 377 to 387 were considered to have the highest probability to be involved in B cell epitopes. The T cell and B cell epitopes identified in this study are promising targets for an epitope-focused, peptide-based HBV vaccine, and provide insight into HBV-induced immune response.

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“…The approaches can be divided into virologic approaches and host immune approaches. With the exceptions of tenofovir alafenamide and besifovir, all other compounds are in pre-clinical or phase I or II trials [184]. Novel therapies with virologic approaches are shown in Fig.…”

Section: Novel Therapiesmentioning

confidence: 99%

Drugs in Development for Hepatitis B

Dawood

Basit

Jayaraj

et al. 2017

Drugs

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With high morbidity and mortality worldwide, there is great interest in effective therapies for chronic hepatitis B (CHB) virus. There are currently several dozen investigational agents being developed for treatment of CHB. They can be broadly divided into two categories: (1) direct-acting antivirals (DAAs) that interfere with a specific step in viral replication; and (2) host-targeting agents that inhibit viral replication by modifying host cell function, with the latter group further divided into the subcategories of immune modulators and agents that target other host functions. Included among the DAAs being developed are RNA interference therapies, covalently closed circular DNA (cccDNA) formation and transcription inhibitors, core/capsid inhibitors, reverse transcriptase inhibitors, hepatitis B surface antigen (HBsAg) release inhibitors, antisense oligonucleotides, and helioxanthin analogues. Included among the host-targeting agents are entry inhibitors, cyclophilin inhibitors, and multiple immunomodulatory agents, including Toll-like receptor agonists, immune checkpoint inhibitors, therapeutic vaccines, engineered T cells, and several cytokine agents, including recombinant human interleukin-7 (CYT107) and SB 9200, a novel therapy that is believed to both have direct antiviral properties and to induce endogenous interferon. In this review we discuss agents that are currently in the clinical stage of development for CHB treatment as well as strategies and agents currently at the evaluation and discovery phase and potential future targets. Effective approaches to CHB may require suppression of viral replication combined with one or more host-targeting agents. Some of the recent research advances have led to the hope that with such a combined approach we may have a functional cure for CHB in the not distant future.

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Review article: novel therapies for hepatitis B virus cure – advances and perspectives

Cited by 51 publications

References 107 publications

Early hepatitis B viral DNA clearance predicts treatment response at week 96

Early hepatitis B viral DNA clearance predicts treatment response at week 96

In Silico Analysis of Epitope-Based Vaccine Candidates against Hepatitis B Virus Polymerase Protein

Drugs in Development for Hepatitis B

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