Measurement of viral interferon sensitivity in patients with chronic hepatitis C. Prospective, randomised, open label phase III clinical trial

Vogel, Wolfgang; Brünner, H.; Lin, Werner; Stauber, Rudolf; Ptacek-Wegerer, Karin; Gschwantler, Michael; Stadler, Bernhard

doi:10.1016/s0168-8278(02)80486-x

Cited by 6 publications

(3 citation statements)

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“…Preliminary data in 60 patients showed no effect of ribavirin on viral disappearance. The increase in viral load in the second part of the week was observed both in patients with or without ribavirin administration [18].…”

Section: Discussionmentioning

confidence: 99%

Twice‐weekly administration of peginterferon‐α‐2b improves viral kinetics in patients with chronic hepatitis C genotype 1

Formann

Jessner

Bennett³

et al. 2003

Journal of Viral Hepatitis

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The decline in hepatitis C viral load on treatment with peginterferon-alpha-2b is not continuous. The aim of this study was to investigate whether twice weekly dosing of peginterferon-alpha-2b may improve viral kinetics. Ten interferon-naïve patients with chronic hepatitis C (genotype 1a or b) were randomized to receive either 1.0 microg/kg peginterferon-alpha-2b once (group A) or twice weekly (group B) for 4 weeks. Viral load and serum concentrations of peginterferon-alpha-2b were measured. Peginterferon-alpha-2b reached maximal blood concentrations 24 h after the first dose, followed by a linear decline during the subsequent days. On the day before administration of the next dose, peginterferon-alpha-2b was undetectable in nine patients in group A (once weekly dosing). The same pattern was observed during the next 3 weeks of therapy. In group B (twice weekly dosing) peginterferon-alpha-2b was detectable at any given time point and higher than in group A (P between 0.01 and <0.0001). Viral load decreased in all patients within 2 days after the first dose of peginterferon-alpha-2b, but increased again on day 3. In group A, it further increased until day 7. A similar pattern was observed in the second week. In contrast, in group B, viral load decreased again on day 4 and remained lower until the end of the study (P < 0.001). To achieve continuous drug exposure and to improve initial viral clearance, peginterferon-alpha-2b has to be given at least two times weekly.

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Section: Discussionmentioning

confidence: 99%

Twice‐weekly administration of peginterferon‐α‐2b improves viral kinetics in patients with chronic hepatitis C genotype 1

Formann

Jessner

Bennett³

et al. 2003

Journal of Viral Hepatitis

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“…Vogel et al . in another preliminary study, demonstrated that the per cent drop in the first 24 h following a single 10 m U dose of IFNα2b or a single dose of PEG‐IFN α2b separated out responders from nonresponders at month 3 of treatment [22]. Patients who cleared virus had a greater than 98% drop in viral levels while those who were nonresponders had a 87–89% decline in viral levels over 24 h.…”

Section: Discussionmentioning

confidence: 99%

“…[20,21] and Vogel et al . [22] provide information that lack of SVR may be predicted in a number of patients as early as 24 h into therapy. In patients who demonstrate a lack of adequate IFN effectiveness, SVR is very unlikely.…”

Section: Discussionmentioning

confidence: 99%

First phase viral kinetic parameters as predictors of treatment response and their influence on the second phase viral decline

Layden

Reddy

et al. 2002

Journal of Viral Hepatitis

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It has recently been shown that upon initiation of interferon (IFN) treatment there is a biphasic decline in hepatitis C virus (HCV) RNA levels. In preliminary results, the rate of second phase viral decline has been shown to be an excellent predictor of treatment response. In this analysis, we determined whether the first phase viral kinetic parameters affected the rate of second phase viral decline. We also assessed whether first phase viral kinetic parameters could be used to predict treatment response within 24 h of initiating treatment. This study is a retrospective analysis of two completed studies from which detailed kinetic data were obtained in patients infected with genotype 1 HCV. In both studies, viral levels were measured frequently over the first 24 h, allowing the determination of IFNs effectiveness in blocking viral production and the viral load at the end of the first phase (v1). The second phase decline slope was calculated by log-linear regression on measurements of serum HCV RNA during days 2, 7 and 14. In study one, sustained viral response (SVR) rates were obtained, allowing the determination of the first phase's predictive power for SVR. Logistic regression and fisher exact tests were used to analyse data. In study one, no patient achieved SVR without an IFN effectiveness greater than 98% and a V1 less than 250 000 copies/mL. When V1 and IFN effectiveness were combined to predict SVR, a negative predictive value= 100%, positive predictive value=71% and accuracy of 95% was obtained after only 24 h of IFN treatment. Both studies illustrated strong correlations for both IFN effectiveness and V1 with the rate of 2nd phase slope (P < 0.001). V1 also correlated significantly with a calculation of infected cell loss (delta), which is a major determinant of the second phase viral decline. These results suggest that early viral kinetics may predict lack of response after only 24 h of treatment initiation and indicate a strong link between the degree of viral load reduction during the first phase, and the subsequent 2nd phase decline slope. This might be explained by a viral dynamics model assuming a jump-start of the immune response when viral loads are reduced below a threshold, subsequently giving rise to a faster 2nd phase decline slope.

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Ribavirin plus interferon versus interferon for chronic hepatitis C

Brok

Gluud

2005

Cochrane Database of Systematic Reviews

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Measurement of viral interferon sensitivity in patients with chronic hepatitis C. Prospective, randomised, open label phase III clinical trial

Cited by 6 publications

References 0 publications

Twice‐weekly administration of peginterferon‐α‐2b improves viral kinetics in patients with chronic hepatitis C genotype 1

Twice‐weekly administration of peginterferon‐α‐2b improves viral kinetics in patients with chronic hepatitis C genotype 1

First phase viral kinetic parameters as predictors of treatment response and their influence on the second phase viral decline

Ribavirin plus interferon versus interferon for chronic hepatitis C

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