Influence of hepatitis B virus genotypes on the intra‐ and extracellular expression of viral DNA and antigens†‡

Sugiyama, Masaya; Tanaka, Yasuhito; Kato, Takanobu; Orito, Etsuro; Ito, Kiyoaki; Acharya, Subrat Kumar; Gish, Robert G.; Kramvis, Anna; Shimada, Takashi; Izumi, Namiki; Kaito, Masahiko; Miyakawa, Yuzo; Mizokami, Masashi

doi:10.1002/hep.21345

Cited by 275 publications

(304 citation statements)

References 51 publications

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“…Sugiyama et al recently reported the intra-and extracellular expression of HBV DNA and antigen [59]. The intracellular expression of HBV DNA and HBcAg were higher for genotypes B and C than genotypes A and D. The extracellular expression of HBV DNA and HBeAg were also higher for genotypes B and C than genotypes A and D (Table 6).…”

Section: Genotype and Subgenotypementioning

confidence: 89%

Role of viral factors in the natural course and therapy of chronic hepatitis B

Kao

2007

Hepatol Int

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Hepatitis B virus (HBV) infection is a global health problem that causes a wide spectrum of liver disease, including acute or fulminant hepatitis, inactive carrier state, chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The pathogenesis of hepatocyte damage associated with HBV is mainly through immune-mediated mechanisms. On the basis of the virus and host interactions, the natural history of HBV carriers who are infected in early life can be divided into four dynamic phases. The frequency, extent, and severity of hepatitis flares or acute exacerbation in the second immune clearance and/or fourth reactivation phase predict liver disease progression in HBV carriers. In the past decade, hepatitis B viral factors including serum HBV DNA level, genotype, and naturally occurring mutants predictive of clinical outcomes have been identified. The higher the serum HBV DNA level after the immune clearance phase, the higher the incidence of adverse outcomes over time. In addition, high viral load, genotype C, basal core promoter mutation, and pre-S deletion correlate with increased risk of cirrhosis and HCC development. As to the treatment of chronic hepatitis B, patients with high HBV DNA level and genotype C or D infection are shown to have a worse response to interferon therapy. In conclusion, serum HBV DNA level, genotype, and naturally occurring mutants are identified to influence liver disease progression and therapy of chronic hepatitis B. More investigations are needed to clarify the molecular mechanisms of the viral factors involved in the pathogenesis of each stage of liver disease and the response to antiviral treatments.

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Section: Genotype and Subgenotypementioning

confidence: 89%

Role of viral factors in the natural course and therapy of chronic hepatitis B

Kao

2007

Hepatol Int

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“…We used the 1.38‐fold‐genome length molecular clone, which contains two copies of the X region (Fig. 2) and therefore has some advantages in replication efficiencies in comparison with the minimum‐length molecular clones 18. We considered it preferable to obtain sufficient replication efficiency of the HBV molecular clones with patient‐derived sequences.…”

Section: Discussionmentioning

confidence: 99%

Resistance mutations of hepatitis B virus in entecavir‐refractory patients

Yamada

Sugiyama

Nitta

et al. 2017

Hepatology Communications

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The emergence of resistance mutations in the reverse transcriptase gene of hepatitis B virus (HBV) is associated with treatment failure. Entecavir (ETV) is one of the most potent anti‐HBV reagents; it has a very low resistance rate and is used as the first‐line treatment for chronic hepatitis B. In this study, we isolated HBVs in 4 ETV‐refractory patients (2 with viral breakthrough, 1 with partial virological response, and 1 with flare‐up) and assessed ETV resistance using replication‐competent 1.38‐fold HBV genome‐length molecular clones. The full genome sequences of infected HBVs in ETV‐refractory patients were determined. The HBV molecular clones were generated with the patient‐derived sequences. After transfection of these molecular clones into HepG2 cells, viral replications and ETV susceptibilities were evaluated by measuring the amount of intracellular core‐particle‐associated HBV DNA using Southern blotting and real‐time polymerase chain reaction. Among these cases, ETV‐resistant variants were detected in 2 patients with viral breakthrough and responsible amino acid mutations in reverse transcriptase were successfully identified in these variants. No ETV‐resistant mutation was detected in the other cases. The identified ETV‐resistant mutations did not confer resistance to tenofovir disoproxil fumarate. Conclusion: The HBV replication model with patient‐derived sequences is useful for assessing replication efficiency, susceptibility to anti‐HBV reagents, and responsible resistance mutations and can aid in choosing the appropriate treatment strategy for treatment‐failure cases of chronic hepatitis B. (Hepatology Communications 2017;1:110‐121)

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“…53,54 This may also explain the clinically milder disease associated with genotype A-infected strains described earlier from India.…”

Section: Hepatitis B Virus Genotypes and Response To Interferon Therapymentioning

confidence: 69%