Meta-analysis Shows Extended Therapy Improves Response of Patients With Chronic Hepatitis C Virus Genotype 1 Infection
ABSTRACT Clinical trials provided conflicting results about whether extended duration of treatment with pegylated interferon-alfa (pegIFN-alfa) and ribavirin (more than 48 weeks) improves rates of sustained virologic response (SVR) in patients infected with hepatitis C virus (HCV) genotype 1 and slow virologic response. We performed a meta-analysis to determine the overall impact of extended treatment, compared with standard treatment, on virologic response rates in these patients.
We performed a literature search to identify randomized controlled trials (RCTs) that included monoinfected, treatment-naive patients infected with HCV genotype 1; data were compared between slow responding patients treated with pegIFN-alfa-2a/b plus ribavirin for 48 weeks and those that received extended treatment (as much as 72 weeks). End points included SVR rates, end-of-treatment (EOT) response and relapse rates; they were calculated according to the DerSimonian-Laird estimate.
Six RCTs assessed the benefits of extended treatment with pegIFN-alfa-2a/b and ribavirin in treatment-naive patients with HCV genotype 1 that were slow responders (n = 669). The extended treatment significantly improved SVR rates in slow responders, compared with the standard of care (14.7% increase in overall SVR; 95% confidence interval, 4%-25.5%; P = .0072). Rates of viral relapse were significantly reduced by extended treatment, but EOT response rates were similar. The frequency of voluntary treatment discontinuation, but not of serious adverse events, was significantly increased by extended therapy.
Extending the duration of treatment with pegIFN-alfa-2a/b and ribavirin in patients with HCV genotype 1 and a slow response to therapy improves the rate of SVR.
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- "Apparently, HCV genotype 1 (and 4) patients with poorresponse IL28B alleles should be considered as difficult to cure patients. Traditional approaches such as prolonged therapy with pegIFN-a and ribavirin are of limited efficacy . In contrast, phase II and III clinical trials have evidenced an enormous potential of telaprevir or boceprevir in combination with pegIFN-a and ribavirin in previous partial non-responders and relapsers to standard therapy  . "
ABSTRACT: Recent genome-wide association studies (GWAS) have identified genetic variations near the IL28B gene which are strongly associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection. Protective IL28B variations are strongly associated with on-treatment viral kinetics and approximately 2-fold increased sustained virologic response (SVR) rates in HCV genotype 1 and 4 patients. In HCV genotype 1 patients, IL28B variations were shown to be the strongest pre-treatment predictor of virologic response. In the treatment of HCV genotype 2 and 3 infected patients, IL28B variations play only a minor role. Preliminary data indicate that IL28B variations are also associated with treatment outcome of regimens, including directly acting antiviral (DAA) agents, though their impact seems to be attenuated compared to standard treatment. Here, we review these important findings and discuss possible implications for clinical decision making in the treatment of HCV infection.Journal of Hepatology 03/2011; 55(3):692-701. DOI:10.1016/j.jhep.2011.03.006 · 10.40 Impact Factor
Conference Paper: Pre-develop bake for end point stabilization with photo-BCB polymers[Show abstract] [Hide abstract]
ABSTRACT: The use of a bake prior to development stabilizes the develop end point of photo-BCB films and removes the time dependence of the develop end point. The elimination of this source of process variability enables the implementation of a develop process in which, for a given film thickness and set of bake conditions, the optimum develop time is a constant, and monitoring of the end point is unnecessaryAdvanced Packaging Materials, 1998. Proceedings. 1998 4th International Symposium on; 04/1998