An escalating dose regime of recombinant interferon-alpha 2A in the treatment of chronic hepatitis C

Bosch, Orencio; Tapia, Luis; Quiroga, Juan Antonio; Carréño, Vicente

doi:10.1016/s0168-8278(05)80029-7

Cited by 32 publications

(10 citation statements)

References 11 publications

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“…These data agree with the findings of previous studies that in patients with chronic hepatitis C, an escalating dosage of IFN-␣ does not improve the overall rate of response. 45,46 However, these results do not exclude that higher response rates can be achieved with an initial higher dosage.…”

Section: Discussionmentioning

confidence: 89%

Quantification of the initial decline of serum hepatitis c virus RNA and response to interferon alfa

et al. 1998

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Although several virus-and host-related predictive factors for the response to interferon alfa (IFN-␣) have been defined in patients with chronic hepatitis C, no pretreatment parameter can definitely predict the response to antiviral treatment. Assessment of the initial response by quantification of serum hepatitis C virus RNA before and 4 weeks after initiation of therapy may be a clinically applicable and reliable parameter to predict long-term response. Therefore, the aims of the present study were to test the predictive value of a decline in HCV RNA of at least 3 log in the first 4 weeks of treatment (⌬HCV RNA) in patients treated with 3 ؋ 10 6 units of recombinant IFN-␣2a (rIFN␣2a) three times per week subcutaneously and to compare ⌬HCV RNA with other established predictive factors, such as HCV genotype and pretreatment viremia. Serum HCV RNA was measured by a validated quantitative reverse transcription-polymerase chain reaction (RT-PCR). Geno/ subtyping of HCV was performed by direct sequencing of the nonstructural (NS) 5B region of PCR-amplified isolates and subsequent phylogenetic analysis. Stable HCV RNA levels (⌬HCV RNA I 1 log) within the first 4 weeks of IFN-␣ treatment were present in 42 of 70 patients. A decline in HCV RNA levels between 1 to 3 log and more than 3 log was observed in 9 (13%) and 19 patients (27%), respectively. In 21 of 70 patients (30%), HCV RNA was not detectable at the end of 12 months' treatment. Three of 26 patients (11%) with a pretreatment viremia of I10 6 copies/mL (all HCV subtype 3a) and 6 of 44 patients (14%) with a pretreatment viremia of G10 6 copies/mL (HCV subtypes 1b, 2a, 2c, 3a [two patients], and 4) achieved a virological sustained response to interferon-␣2a treatment. All patients with a virological sustained response had an initial ⌬HCV RNA of more than 3 log. In a stepwise discriminant-function analysis, the initial ⌬HCV RNA was confirmed as the strongest predictor of virological sustained response (P F .0001). In conclusion, the data of the present study suggest that IFN-␣ treatment can be terminated after 4 weeks in patients with a decrease in HCV RNA levels of less than 3 log, when apparent HCV eradication is considered the therapeutic target. The predictive value of ⌬HCV RNA clearly exceeds the significance of HCV genotype and pretreatment viremia as predictors of successful

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Section: Discussionmentioning

confidence: 89%

Quantification of the initial decline of serum hepatitis c virus RNA and response to interferon alfa

et al. 1998

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“…It has been shown to be effective, although initially the relapse rate upon discontinuation of therapy was disappointingly high, with sustained virological response of only 8%-12% [4-6]. Further evidence suggested that increasing the duration of IFN therapy to 12-18 months [5-12] and using larger doses of IFN [9,[13][14][15][16][17] improves the rate of sustained response. Analysis of newer data suggests that daily dosing, or providing a high-dose induction period followed by maintenance therapy, may im-…”

mentioning

confidence: 99%

The Protein Kinase–Interacting Domain in the Hepatitis C Virus Envelope Glycoprotein–2 Gene Is Highly Conserved in Genotype 1–Infected Patients Treated with Interferon

et al. 2000

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The hepatitis C virus (HCV) envelope glycoprotein-2 inhibits the interferon (IFN)-induced, double-stranded RNA-activated protein kinase (PKR) via the PKR eukaryotic initiation factor-2alpha phosphorylation homology domain (PePHD). The present study examined the genetic variability of the PePHD in patients receiving IFN therapy. The PePHD from 12 HCV genotype 1 (HCV-1)-infected patients receiving daily IFN therapy was amplified by reverse-transcriptase polymerase chain reaction and analyzed by direct and clonal sequencing. The PePHD was highly conserved in 38 HCV GenBank isolates. There was no difference in pretreatment PePHD sequences isolated from IFN responders versus nonresponders. The major PePHD quasi-species variant did not change after 6 weeks of daily IFN therapy, and in 1 patient the major quasi-species variant did not change during 9 months of observation. Sequencing of 25 pretreatment PePHD clones from 3 patients confirmed that there was extremely low sequence variability surrounding the PePHD. The PePHD is highly conserved in HCV-1-infected IFN responders and nonresponders and does not appear to evolve in response to IFN therapy.

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“…Interferon alfa-2b (IFN-␣) therapy has been shown to be effective for viral hepatitis caused by HBV 8 or HCV [9][10][11][12][13] in nonimmunosuppressed patients. This treatment has been less effective in virally infected liver allograft recipients.…”

mentioning

confidence: 99%

Incidence and severity of acute allograft rejection in liver transplant recipients treated with alfa interferon

et al. 1998

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An escalating dose regime of recombinant interferon-alpha 2A in the treatment of chronic hepatitis C

Cited by 32 publications

References 11 publications

Quantification of the initial decline of serum hepatitis c virus RNA and response to interferon alfa

Quantification of the initial decline of serum hepatitis c virus RNA and response to interferon alfa

The Protein Kinase–Interacting Domain in the Hepatitis C Virus Envelope Glycoprotein–2 Gene Is Highly Conserved in Genotype 1–Infected Patients Treated with Interferon

Incidence and severity of acute allograft rejection in liver transplant recipients treated with alfa interferon

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