Quasispecies as predictive factor of rapid, early and sustained virological responses in chronic hepatitis C, genotype 1, treated with peginterferon–ribavirin

Salmerón, Javier; Casado, J.; Rueda, Paloma; Lafuente, Víctor de; Diago, M.; Romero‐Gómez, Manuel; Palacios, A.; León, Josefa; Gila, A.; Quiles-Pérez, Rosa; Rodríguez, Luis Ramón Ruiz; Ruiz-Extremera, Ángeles

doi:10.1016/j.jcv.2007.11.023

Cited by 16 publications

(13 citation statements)

References 21 publications

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“…The current regression analysis suggests that among both coinfected and monoinfected subjects, baseline HCV complexity is an independent factor in achieving EVR. Other investigators have noted an association between treatment response and baseline quasispecies complexity among HCV monoinfected subjects [20, 21, 22]. There was no difference in quasispecies complexity as analyzed at baseline prior to treatment assignment in the entire cohort.…”

Section: Discussionmentioning

confidence: 66%

Hepatitis C Virus (HCV) Quasispecies Complexity and Selection in HCV/HIV‐Coinfected Subjects Treated with Interferon‐Based Regimens

et al. 2010

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HCV/HIV coinfection has emerged as a major cause of morbidity and mortality due to liver disease. Interferon-based therapy response rates have been disappointingly low. Baseline HCV complexity and the relationship between complexity and viral kinetic parameters has not been well described in HCV/HIV subjects. A subset of patients enrolled in ACTG 5071 underwent sampling to evaluate viral kinetics and HCV complexity changes. Early kinetic parameters, baseline complexity, and treatment outcomes, including rapid (RVR), early (EVR), and sustained (SVR) viral response were evaluated. HCV monoinfected subjects were matched to HCV/HIV coinfected subjects. RESULTS Baseline complexity was determined in 108 HCV/HIV coinfected subjects and 13 HCV controls. Quasispecies complexity was 2.24 in HCV/HIV and 1.90 in monoinfected subjects (p=0.14). Lower baseline complexity was associated with EVR (p=0.04) and approached significance for SVR. In patients who underwent viral kinetic modeling, complexity decrease was associated with RVR (p= 0.03), and was independent of the correlation between first phase viral decline efficiency and RVR. CONCLUSION Baseline HCV complexity is an independent predictor of early viral response in HCV/HIV subjects. Complexity decrease occurs by 4 weeks of interferon-based therapy and is associated with RVR. These findings may enhance predictive modeling of treatment outcomes in HCV/HIV patients.

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Section: Discussionmentioning

confidence: 66%

Hepatitis C Virus (HCV) Quasispecies Complexity and Selection in HCV/HIV‐Coinfected Subjects Treated with Interferon‐Based Regimens

et al. 2010

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“…Significant factors associated with SVR are the baseline HCV load and genotype. Despite HCV quasispecies and treatment response being a controversial topic, HCV quasispecies complexity before therapy has been independently associated with treatment response (1,7,8,10,29,31,36,43,45). However, although prior studies have demonstrated correlations in the genetic complexity of HCV hypervariable region 1 (HVR1) at the baseline and nonresponse to IFN-based therapy (31), other studies have found that HVR1 genetic complexity or heterogeneity did not correlate with HCV susceptibility to IFN-based therapy (23,38).…”

Section: Discussionmentioning

confidence: 99%

Complexity and Catalytic Efficiency of Hepatitis C Virus (HCV) NS3 and NS4A Protease Quasispecies Influence Responsiveness to Treatment with Pegylated Interferon plus Ribavirin in HCV/HIV-Coinfected Patients

Aparicio

Franco

Parera

et al. 2011

J Virol

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Hepatitis C virus (HCV) nonstructural protein 3 (NS3) contains a serine protease that cleaves the virus-encoded polyprotein and inactivates cellular proteins required for innate immunity. HCV NS3/4A protease functions as an antagonist of virus-induced interferon (IFN) regulatory factor 3 activation and IFN-␤ expression through its ability to block retinoic acid-inducible gen I (RIG-I) and Toll-like receptor 3 signaling by cleaving caspase recruitment domain adaptor-inducing IFN-␤ (Cardif) and Toll/interleukin-1 (IL-1) receptor domain-containing adaptor-inducing IFN proteins, respectively. NS3/4A protease activity allows the virus to evade the cellular innate immune response, which may influence the subsequent development of adaptive immunity to HCV, virus persistence, and the response to IFNbased therapy (21).HCV is the causal agent of chronic liver infection, which afflicts more than 170 million people worldwide

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“…Other viral factors associated with SVR include the degree of viral quasi-species complexity [178][179][180] and the number of mutations within specific regions of the HCV genome (i.e. the NS5A region) [181][182][183].…”

Section: Virologic Parametersmentioning

confidence: 99%

Treatment predictors of a sustained virologic response in hepatitis B and C

Kau

Vermehren

Sarrazin

2008

Journal of Hepatology

294

212

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Treatment predictors are important tools for the management of therapy in patients with chronic hepatitis B and C virus (HBV, HCV) infection. In chronic hepatitis B, several pretreatment parameters have been identified for prediction of virologic response to interferon alfa-based antiviral therapies or treatment with polymerase inhibitors. In interferon alfa and pegylated interferon alfa-treated patients, low baseline HBV DNA concentrations, HBV genotype A (B), and high baseline ALT levels are significantly associated with treatment response. In patients treated with nucleos(t)ide analogues, low baseline HBV DNA but not viral genotype is positively associated with virologic response. During treatment the best predictor of response is HBV DNA kinetics. Early viral suppression is associated with favourable virologic response and reduced risk for subsequent resistance mutations. For the current standard treatment with pegylated interferon alfa and ribavirin in patients with chronic hepatitis C, infection with HCV genotypes 2 and 3, baseline viral load below 400,000-800,000 IU/ml, Asian and Caucasian ethnicity, younger age, low GGT levels, absence of advanced fibrosis/cirrhosis, and absence of steatosis in the liver have been identified as independent pretreatment predictors of a sustained virologic response. After initiation of treatment, initial viral decline with undetectable HCV-RNA at week 4 of therapy (RVR) is the best predictor of sustained virologic response independent of HCV genotype.

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Quasispecies as predictive factor of rapid, early and sustained virological responses in chronic hepatitis C, genotype 1, treated with peginterferon–ribavirin

Cited by 16 publications

References 21 publications

Hepatitis C Virus (HCV) Quasispecies Complexity and Selection in HCV/HIV‐Coinfected Subjects Treated with Interferon‐Based Regimens

Hepatitis C Virus (HCV) Quasispecies Complexity and Selection in HCV/HIV‐Coinfected Subjects Treated with Interferon‐Based Regimens

Complexity and Catalytic Efficiency of Hepatitis C Virus (HCV) NS3 and NS4A Protease Quasispecies Influence Responsiveness to Treatment with Pegylated Interferon plus Ribavirin in HCV/HIV-Coinfected Patients

Treatment predictors of a sustained virologic response in hepatitis B and C

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