Is an ?� la carte? combination interferon alfa-2b plus ribavirin regimen possible for the first line treatment in patients with chronic hepatitis C?

Poynard, Thierry; McHutchison, John G.; Goodman, Zachary; Ling, Mei-Hsiu; Albrecht, Janice K.

doi:10.1002/hep.510310131

Cited by 337 publications

(261 citation statements)

References 17 publications

(17 reference statements)

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“…Quasispecies in NS5A region of HCV as predictors of response to therapy. HCV genotype 1, particularly genotype 1b, are most resistant to combined IFN-R therapy [5] . Among viral factors, genetic variability has been studied in many regions of the HCV genome, mainly in hypervariable region 1 (HVR1) and PKR-eIF2α phosphorylation homology domain (PePHD) of E2 region and in PKRbd (including ISDR) of NS5A [17,22,[39][40][41][42][43] .…”

Section: Variability In Six Different Regions Along the Ns5a Genementioning

confidence: 99%

“…Current combination therapy of pegylated interferon (IFN) alpha and ribavirin (IFN-R) is not universally effective in patients with chronic hepatitis C; patients infected with genotypes 2 or 3 show a high rate of sustained virological response (SVR) (90%) whereas the HCV genotype 1 infected patients have the lowest level of SVR (40% to 50%) [2][3][4] . Factors that can predict the response to antiviral therapy are not well established; the accepted predictive parameters are: age, sex, pre-treatment viral load, fibrosis stage and HCV genotype [5] . Numerous studies have been undertaken to explain the resistance of genotype 1-infected patients to IFN therapy.…”

Section: Introductionmentioning

confidence: 99%

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Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b during interferon or combined interferon-ribavirin therapy

Veillon

Payan²,

Guillou‐Guillemette³

et al. 2007

WJG

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AIM:To evaluate the implication of substitutions in the hepatitis C virus (HCV) non-structural 5A (NS5A) protein in the resistance of HCV during mono-interferon (IFN) or combined IFN-ribavirin (IFN-R) therapy. Although NS5A has been reported to interact with the HCV RNAdependent RNA polymerase, NS5B, as well as with many cellular proteins, the function of NS5A in the life cycle of HCV remains unclear.METHODS: HCV quasispecies were studied by cloning and sequencing of sequential isolates from patients infected by HCV genotype 1b. Patients were treated by IFN-α2b for 3 mo followed by IFN-α2b alone or combined IFN-R therapy for 9 additional months. Patients were categorized intro two groups based on their response to the treatments: 7 with sustained virological response (SVR) (quasispecies = 150) and 3 non-responders (NR) to IFN-R (quasispecies = 106). RESULTS:Prior to treatment, SVR patients displayed a lower complexity of quasispecies than NR patients. Most patients had a decrease in the complexity of quasispecies during therapy. Analysis of amino acids substitutions showed that the degree of the complexity of the interferon sensitivity-determining region (ISDR) and the V3 domain of NS5A protein was able to discriminate the two groups of patients. Moreover, SVR patients displayed more variability in the NS5A region than NR patients. CONCLUSION:These results suggest that detailed molecular analysis of the NS5A region may be important for understanding its function in IFN response during HCV 1b infection.

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Section: Variability In Six Different Regions Along the Ns5a Genementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b during interferon or combined interferon-ribavirin therapy

Veillon

Payan²,

Guillou‐Guillemette³

et al. 2007

WJG

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“…Los pacientes con genotipos 2, 3 y 5 representan sólo el 3,8, 11,6 y 3,8%, del total del grupo estudiado, respectivamente, por lo que no es posible llegar a conclusiones sobre la infl uencia del genotipo en la RVS en nuestro estudio. A diferencia de estudios previos, en nuestro trabajo no se observó una mayor tasa de respuesta al tratamiento en pacientes de género femenino 12 . Por el contrario, se consiguió una RVS en 56% de los hombres versus 36% en las mujeres, que si bien no alcanza signifi cancia estadística, muestra una clara tendencia.…”

Section: Discussionunclassified

“…De los pacientes respondedores, sólo 13% de ellos tenía fi brosis F3 y F4 del score Metavir, y 87% restante correspondían a F0 y F1, siendo un importante predictor de respuesta la ausencia de fi brosis signifi cativa. Esta situación está ampliamente descrita en la literatura, en que el parámetro histológico es otro de los principales factores independientes predictivos de RVS, tanto en análisis univariado como multivariado 5,[12][13][14] .…”

Section: Discussionunclassified

Resultados del tratamiento con peginterferón alfa-2a y ribavirina en pacientes con hepatitis crónica C

et al. 2011

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“…It is known that approximately 60% of the patients infected with HCV genotype 1 and nearly 40% of those infected with genotype 3 do not achieve an SVR when treated with the conventional regimen of IFN and RBV [2][3][4][5][6][7]. The availability of PEG-IFNs has reduced the percentage of patients experiencing treatment failure.…”

mentioning

confidence: 99%

Retreatment of hepatitis C patients who previously experienced treatment failure

Gonçales

Lopes²

2007

Braz J Infect Dis

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In its different formulations, interferon (IFN) alpha combined with ribavirin (RBV) is the best treatment alternative for patients infected with the hepatitis C virus (HCV) [1]. In such patients, the objective is to achieve an end-of-treatment virological response -negative serum HCV ribonucleic acid (RNA) -followed by a sustained virological response (SVR), which is defined as HCV RNA negativity for six months after the suspension of treatment.The treatment regimens for HCV infection have evolved from monotherapy with conventional IFN alpha to combined therapy with IFN and RBV and, more recently, to combined therapy with pegylated IFN (PEG-IFN alpha-2a or alpha-2b) and RBV [2,3]. It is known that approximately 60% of the patients infected with HCV genotype 1 and nearly 40% of those infected with genotype 3 do not achieve an SVR when treated with the conventional regimen of . The availability of PEG-IFNs has reduced the percentage of patients experiencing treatment failure. In large international trials involving treatment-naïve patients, regimens that include the combination of PEG-IFN and RBV have produced significantly higher rates of SVR than those observed with the use of the conventional combination of IFN and RBV (54-56% vs. 44-47%) [5][6][7].Similar to what occurs in treatment-naïve patients, retreatment provides the patient with a new chance to achieve an SVR. Long-term studies have proven that the vast majority of the patients who achieve an SVR usually remain negative for HCV RNA for a long time [8].The arguments in favor of retreating patients would be the possibility of eradicating HCV, reducing fibrosis, and decreasing the risk of evolving to hepatocarcinoma. With regard to the new antiviral agents, we do not know when they will be available or whether all patients will be able to wait several years to initiate retreatment.It is known that patients who experience relapse after treatment with conventional IFN, with or without RBV, respond better to retreatment with PEG-IFN alpha and RBV than do those presenting no response to treatment with conventional IFN (with or without RBV). Krawitt et al. observed an SVR rate of 55% in 66 relapsing patients who were retreated with PEG-IFN alpha-2b (100-150 µg/week) and RBV (1000 mg/day), compared with only 20% in 116 previous nonresponders treated with the same regimen [9]. An SVR was observed in 53% of the relapsing patients infected with genotype 1, compared with 59% of the relapsing patients infected with genotypes 2 or 3. There were, therefore, no significant differences between these groups of patients. This was not observed in the previous nonresponders receiving retreatment. Of those, only 17% of the individuals infected with genotype 1, in comparison with 57% of the individuals infected with genotypes 2 or 3, achieved an SVR. Therefore, genotype had an influence on SVR in the previous nonresponders who underwent retreatment.Studies conducted in Brazil and involving nonresponders to IFN/RBV demonstrated SVR rates resulting from retreatment with the PEG-...

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Is an ?� la carte? combination interferon alfa-2b plus ribavirin regimen possible for the first line treatment in patients with chronic hepatitis C?

Cited by 337 publications

References 17 publications

Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b during interferon or combined interferon-ribavirin therapy

Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b during interferon or combined interferon-ribavirin therapy

Resultados del tratamiento con peginterferón alfa-2a y ribavirina en pacientes con hepatitis crónica C

Retreatment of hepatitis C patients who previously experienced treatment failure

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