Adding interferon to lamivudine enhances the early virologic response and reversion of the precore mutation in difficult-to-treat HBV infection

Yuki, Nobukazu; Nagaoka, Takayuki; Nukui, Kazuhiko; Omura, Masao; Hikiji, Kazumasa; Kato, Masaaki

doi:10.1007/s00535-008-2174-9

Cited by 10 publications

(12 citation statements)

References 18 publications

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“…Our results are compatible with these findings. Also, it has been reported that during the course of antiviral therapy, reversions from PC/BCP mutants to wild type HBV may occur (21, 22). In summary, in the current study, there is a relationship between mutation in the precore region and high viral load, which can involve in severity of liver damage.…”

Section: Discussionmentioning

confidence: 99%

Correlation Between Viral Load of HBV in Chronic Hepatitis B Patients and Precore and Basal Core Promoter Mutations

et al. 2013

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BackgroundMore than two billion people have been exposed to hepatitis B virus (HBV) worldwide. Furthermore, four hundred million of them are infected with chronic HBV infection. The predominant mutation of the precore region involves a G to A change at nucleotide1896, which creates a premature stop codon at codon 28. Two mutations of A1762T and G1764A are reported as the most prevalent mutations in the basal core promoter (BCP).ObjectivesThe purpose of this study was to investigate the relationship between mutations in precore (PC) and basal core promoter regions, and the viral load.Patients and MethodsFifty serum samples from patients with hepatitis B were used. Levels of liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured at the same time of serological markers of hepatitis B by ELISA. HBV-DNA was extracted from the sera, and then PCR performed on the HBV-DNA extracted with the use of specific primer of gene C. HBV viral load was determined by real-time PCR. The PC/ BCP mutations were determined by applying Line Probe Assay technique. The data were analyzed using SPSS software, version 20.ResultsOnly 82% of the patients were HBeAb positive and 76% of the patients had basal core/ precore mutations and mean viral load was 3/7 × 106 ± 9/7 × 105 IU/ml. Prevalence of mutations in the precore and basal core promoter regions were 46% and 30%, respectively.ConclusionsOur data indicated that there is a statistically significant relationship between HBV viral load and mutations in precore region (P < 0.05).

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Section: Discussionmentioning

confidence: 99%

Correlation Between Viral Load of HBV in Chronic Hepatitis B Patients and Precore and Basal Core Promoter Mutations

et al. 2013

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“…Antigen was only rarely visualized in bronchiolar epithelium and was not found in VOL. 83,2009 INFLUENZA VIRUS PATHOGENESIS IN GUINEA PIGS 2857 alveolar cells. This lack of virus antigen, along with moderate lung titers and the focal lung pathology among H5N1 and 1918 virus-infected guinea pigs, suggests that sites of virus replication are more restricted in the guinea pig lung than in other animal models.…”

Section: Discussionmentioning

confidence: 99%

Pathogenesis of 1918 Pandemic and H5N1 Influenza Virus Infections in a Guinea Pig Model: Antiviral Potential of Exogenous Alpha Interferon To Reduce Virus Shedding

Hoeven

Belser

Szretter

et al. 2009

J Virol

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Although highly pathogenic avian influenza H5N1 viruses have yet to acquire the ability to transmit efficiently among humans, the increasing genetic diversity among these viruses and continued outbreaks in avian species underscore the need for more effective measures for the control and prevention of human H5N1 virus infection. Additional small animal models with which therapeutic approaches against virulent influenza viruses can be evaluated are needed. In this study, we used the guinea pig model to evaluate the relative virulence of selected avian and human influenza A viruses. We demonstrate that guinea pigs can be infected with avian and human influenza viruses, resulting in high titers of virus shedding in nasal washes for up to 5 days postinoculation (p.i.) and in lung tissue of inoculated animals. However, other physiologic indicators typically associated with virulent influenza virus strains were absent in this species. We evaluated the ability of intranasal treatment with human alpha interferon (␣-IFN) to reduce lung and nasal wash titers in guinea pigs challenged with the reconstructed 1918 pandemic H1N1 virus or a contemporary H5N1 virus. IFN treatment initiated 1 day prior to challenge significantly reduced or prevented infection of guinea pigs by both viruses, as measured by virus titer determination and seroconversion. The expression of the antiviral Mx protein in lung tissue correlated with the reduction of virus titers. We propose that the guinea pig may serve as a useful small animal model for testing the efficacy of antiviral compounds and that ␣-IFN treatment may be a useful antiviral strategy against highly virulent strains with pandemic potential.

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“…In one report, combination of interferon-α with LMV for 24 weeks followed by LMV alone for 28 weeks resulted in 90% complete virologic response rate at week 8, compared with 33% in the LMV monotherapy group. At week 52, YMDD mutants were detected in 8% of patients on combination therapy versus 30% on the monotherapy [44]. In another study, interferon was used to reduce the viral load to less than 10 3 copies/mL; LMV was then added for 1 month, and continued as monotherapy for 24 months.…”

Section: Prevention Of Drug Resistancementioning

confidence: 97%

HBV Drug Resistance Development, Testing, and Prevention

2010

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Chronic infection by hepatitis B virus (HBV) can result in cirrhosis, hepatic failure, and hepatocellular carcinoma (HCC) if left untreated. The extent of liver injury and the risk of HCC closely correlate with active viral replication, as indicated by high levels of circulating HBV DNA. Five oral antiviral agents, each targeting the viral DNA polymerase, are currently available in the United States to inhibit viral replication. Their effective use requires proper monitoring of drug resistance development. The current clinical guidelines recommend measuring "total" circulating HBV DNA to evaluate the efficacy of treatment and to serve as an indirect measure of drugresistant mutant viruses. This may result in delayed identification of drug-resistant mutants that can cause hepatic injuries and decompensation. This review discusses the virologic mechanisms of drug resistance, the need and strategies for early detection of mutant viruses, and the recent studies on the prevention of drug resistance.

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Adding interferon to lamivudine enhances the early virologic response and reversion of the precore mutation in difficult-to-treat HBV infection

Cited by 10 publications

References 18 publications

Correlation Between Viral Load of HBV in Chronic Hepatitis B Patients and Precore and Basal Core Promoter Mutations

Correlation Between Viral Load of HBV in Chronic Hepatitis B Patients and Precore and Basal Core Promoter Mutations

Pathogenesis of 1918 Pandemic and H5N1 Influenza Virus Infections in a Guinea Pig Model: Antiviral Potential of Exogenous Alpha Interferon To Reduce Virus Shedding

HBV Drug Resistance Development, Testing, and Prevention

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