γ-Glutamyltransferase and rapid virological response as predictors of successful treatment with experimental or standard peginterferon-α-2b in chronic hepatitis C non-responders
Article first published online: 15 AUG 2007
Volume 27, Issue 9, pages 1217–1225, November 2007
How to Cite
Bergmann, J. F., Vrolijk, J. M., Van Der Schaar, P., Vroom, B., Van Hoek, B., Van Der Sluys Veer, A., De Vries, R. A., Verhey, E., Hansen, B. E., Brouwer, J. T., Janssen, H. L. A., Schalm, S. W. and De Knegt, R. J. (2007), γ-Glutamyltransferase and rapid virological response as predictors of successful treatment with experimental or standard peginterferon-α-2b in chronic hepatitis C non-responders. Liver International, 27: 1217–1225. doi: 10.1111/j.1478-3231.2007.01540.x
- Issue published online: 15 AUG 2007
- Article first published online: 15 AUG 2007
- Received 26 April 2007accepted 15 May 2007
- peginterferon induction;
- hepatitis C virus;
Background: High-dose peginterferon-α (PegIFN-α) induction and prolongation of therapy may be an option to improve sustained virological response (SVR) rates among hepatitis C virus (HCV) non-responders, although a higher and a longer dosing of PegIFN-α may intensify side effects.
Methods: We randomized 53 patients, who previously failed with standard IFN-α±ribavirin, to a high-dose induction and an extended regimen with PegIFN-α-2b [3.0 μg/kg once weekly (q.w.) 12 weeks2.0 μg/kg q.w. 12 weeks1.5 μg/kg q.w. 48 weeks] or a standard regimen (1.5 μg/kg q.w. 48 weeks). All patients received daily weight-based ribavirin (800–1200 mg/day). The short-form 36 health survey was used to evaluate health-related quality of life (HRQL).
Results: Intention-to-treat analysis showed no significant difference in SVR rate (44% vs. 37%, P=0.62) and relapse rate (9% vs. 31%, P=0.17) between experimental and standard treatment. Overall, 80% of the [positive predictive value (PPV)] patients with rapid virological response (RVR, HCV-RNA negativity at week 4) achieved SVR. No significant dose-related differences in HRQL were seen between both groups. At baseline, genotype 2 or 3 [odds ratio (OR): 7.4, 95% confidence interval (CI): 1.4–33.3, P=0.01] and γ-glutamyltransferase (GGT) levels <2 × ULN (upper limit of normal) (OR: 6.76, 95% CI: 1.5–31.3, P=0.009) were significantly associated with SVR. Multivariate logistic regression at week 4 showed that only baseline GGT <2 × ULN (OR: 7.3, 95% CI: 1.4–38.5, P=0.01) and RVR (OR: 15.6, 95% CI: 3.2–76.9, P<0.001) were independently predictive for SVR.
Conclusion: Retreatment with PegIFN-α-2b and ribavirin for a minimum of 48 weeks should be considered in all patients unresponsive to previous IFN-based therapies. Baseline GGT values and RVR are highly predictive for retreatment outcome.