Efficacy of interferon dose and prediction of response in chronic hepatitis C: Benelux study in 336 patients

Brouwer, Johannes T.; Nevens, Frederik; Kleter, Bernhard; Elewaut, André; Alder, Mike; Brenard, R.; Chamuleau, R. A. F. M.; Michielsen, P.; Pirotte, Jean; Hautekèete, M.; Weber, Joseph; Bourgeois, Nadine; Hansen, Bettina E.; Bronkhorst, Carolien C.M.; Kate, F. J. W. Ten; Heijtink, Rudolf R.A.; Fevery, Johan; Schalm, Solko W.

doi:10.1016/s0168-8278(98)80342-5

Cited by 41 publications

(22 citation statements)

References 33 publications

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“…Although induction leads to a higher initial response, this effect is often lost after dose reduction [20][21][22][23]. Prolonged induction treatment is still under consideration [24,25].…”

Section: Discussionmentioning

confidence: 99%

Reduction of relapse rates by 18-month treatment in chronic hepatitis C. A Benelux randomized trial in 300 patients☆

Brouwer

Nevens²,

Bekkering

et al. 2004

Journal of Hepatology

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“…Although induction leads to a higher initial response, this effect is often lost after dose reduction [20][21][22][23]. Prolonged induction treatment is still under consideration [24,25].…”

Section: Discussionmentioning

confidence: 99%

Reduction of relapse rates by 18-month treatment in chronic hepatitis C. A Benelux randomized trial in 300 patients☆

Brouwer

Nevens²,

Bekkering

et al. 2004

Journal of Hepatology

Self Cite

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“…The treatment of choice is interferon-␣ (IFN-␣ ), that has proven antiinflammatory and antiviral efficacy [Davis et al, 1989;Di Bisceglie et al, 1989;Malaguarnera et al, 1995]. The proportion of patients responding to therapy in terms of a sustained virological response is relatively low, however, varying around 15% [Brouwer et al, 1998;Lindsay, 1997;Reichard et al, 1998]. Some investigators described an IFN-␣ dose-dependent clearance of hepatitis C virus (HCV) RNA from serum [Lam et al, 1997;Neumann et al, 1998, Zeuzem et al, 1998].…”

Section: Introductionmentioning

confidence: 99%

MxA gene expression in peripheral blood mononuclear cells from patients infected chronically with hepatitis C virus treated with interferon-?

Meier¹,

Mihm²,

Ramadori³

2000

J. Med. Virol.

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Hepatitis C virus (HCV) infection causes acute and often chronic liver disease. The treatment of choice is interferon-alpha (IFN-alpha). The proportion of patients responding to therapy in terms of a sustained virological response, however, is relatively low. One possible reason for the lack of effectiveness might be neutralization of the drug by host's inhibitory factors. Recent kinetic studies suggested that high doses of IFN-alpha-, especially during the initial phase of therapy, might improve the virological response rates. Eighteen patients infected chronically with HCV were treated with IFN-alpha either at a standard dose (3 x 10(6) to 6 x 10(6) IU IFN-alpha three times weekly) for 6 to 12 months or with an intensified therapy (6 x 10(6) IU IFN-alpha daily) for at least one month. As surrogate parameter for the intracellular effect of the drug, MxA gene expression was quantified in RNA preparations from peripheral blood mononuclear cells. Beta-2-microglobulin (beta2M) concentrations were measured in serum. Serum HCV RNA titers were monitored in parallel. When compared to healthy individuals, untreated patients infected chronically with HCV were found to express 2.8-fold higher amounts of MxA specific transcripts. MxA gene expression and serum beta2M concentrations were found to be induced after administration of IFN-alpha, independent of the virological response not only during the initial phase of the intensified therapy but also over several months during standard therapy. It is concluded from these results that both early non-effectiveness of high dose IFN-alpha therapy as well as long-term non-effectiveness of standard therapy are not due to IFN-alpha inhibitory or neutralizing elements in serum.

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“…All patients met the inclusion and exclusion criteria previously described [10]. Note that all patients in these studies were considered "difficult-to-treat", either because they were non-responders to previous treatment or had cirrhosis and/or high baseline viral load.…”

Section: Methodsmentioning

confidence: 99%

Changes in anti-viral effectiveness of interferon after dose reduction in chronic hepatitis c patients: a case control study

et al. 2001

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BackgroundHigh dose interferon induction treatment of hepatitis C viral infection blocks viral production over 95%. Since dose reduction is often performed due to clinical considerations, the effect of dose reduction on hepatitis C virus kinetics was studied.MethodsA new model that allowed longitudinal changes in the parameters of viral dynamics was used in a group of genotype-1 patients (N = 15) with dose reduction from 10 to 3 million units of interferon daily in combination with ribavirin, in comparison to a control group (N = 9) with no dose reduction.ResultsDose reduction gave rise to a complex viral kinetic pattern, which could be only explained by a decrease in interferon effectiveness in blocking virion production. The benefit of the rapid initial viral decline following the high induction dose is lost after dose reduction. In addition, in some patients also the second phase viral decline slope, which is highly predictive of success of treatment, was impaired by the dose reduction resulting in smaller percentage of viral clearance in the dose reduction group.ConclusionsThese findings, while explaining the failure of many induction schedules, suggest that for genotype-1 patients induction therapy should be continued till HCVRNA negativity in serum in order to increase the sustained response rate for chronic hepatitis C.

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Efficacy of interferon dose and prediction of response in chronic hepatitis C: Benelux study in 336 patients

Cited by 41 publications

References 33 publications

Reduction of relapse rates by 18-month treatment in chronic hepatitis C. A Benelux randomized trial in 300 patients☆

Reduction of relapse rates by 18-month treatment in chronic hepatitis C. A Benelux randomized trial in 300 patients☆

MxA gene expression in peripheral blood mononuclear cells from patients infected chronically with hepatitis C virus treated with interferon-?

Changes in anti-viral effectiveness of interferon after dose reduction in chronic hepatitis c patients: a case control study

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