The safety and efficacy of pegylated interferon (PEG-IFN) alfa-2a and ribavirin were studied among patients treated for genotype 4 chronic hepatitis C. Ninety-five patients with chronic hepatitis C genotype 4 were treated with PEG-IFN alfa-2a (180 microg/week) plus ribavirin (> or =11 mg/kg/day) for 48 weeks. The primary end point was sustained virological response, defined as non-detectable levels of HCV RNA at the end of follow up (week 72). The proportion with sustained virological response was 58/95 = 61.1% (95% CI = 50.5-70.9%). Side effects were generally mild, well managed by dose reductions (in 62% of patients); in only two patients were side effects sufficiently severe to require treatment interruption. Ninety percent of patients adhered to treatment up to week 12, and their sustained virological response rate was higher compared to non-adherent (65% vs. 22%, respectively, P = 0.012). None of the patients who failed to achieve 1 log reduction of viral load by week 8 (n = 15), or 2 log reduction by week 12 (n = 17), had a sustained virological response. In conclusion, sustained virological response in genotype 4 Egyptian patients treated with PEG-IFN alfa-2a and ribavirin was estimated around 60%, intermediate between sustained virological response observed in genotype 1 and genotype 2-3 patients in Western countries. The early virological response (week 4 or week 8) should be investigated as a criterion to decide whether the patient may benefit from a shorter duration of therapy.
"Factors associated with SVR to interferon treatment have not been fully investigated in HCV genotype 4 infected patients. Previous studies demonstrated that age, body weight, baseline ALT, baseline HCV RNA viral load, HCV genotype and the level of fibrosis or cirrhosis are some predictors of response [8-12]. However, recent studies indicated that cytokines could be used as markers for disease progression in HCV infected patients . "
[Show abstract][Hide abstract] ABSTRACT: Combined pegylated interferon-alpha and ribavirin therapy has sustained virological response (SVR) rates of 54% to 61%. Pretreatment predictors of SVR to interferon therapy have not been fully investigated yet. The current study assesses a group of chemokines that may predict treatment response in Egyptian patients with chronic HCV infection.Patients and methods: CXCL5, CXCL9, CXCL11, CXCL12, CXCL 13, CXCL 16 chemokines and E-Cadherin were assayed in 57 chronic HCV patients' sera using quantitative ELISA plate method. All studied patients were scheduled for combined pegylated interferon alpha and ribavirin therapy (32 patients received pegylated interferon alpha 2b, and 25 patients received pegylated interferon alpha 2a). Quantitative hepatitis C virus RNA was done by real time RT-PCR and HCV genotyping by INNOLIPAII.
There was no significant difference (p > 0.05) in baseline HCV RNA levels between responders and non-responders to interferon. A statistically significant difference in CXCL13 (p = 0.017) and E-Cadherin levels (P = 0.041) was reported between responders and nonresponders at week 12. Significant correlations were found between changes in the CXCL13 levels and CXCL9, CXCL16, E-cadherin levels as well as between changes in E-cadherin levels and both CXCL16 and ALT levels that were maintained during follow up. Also, significant changes have been found in the serum levels of CXCL5, CXCL13, and CXCL16 with time (before pegylated interferon alpha 2 a and alpha 2 b therapy, and at weeks 12 and 24) with no significant difference in relation to interferon type and response to treatment.
Serum levels of CXCL13 and E-Cadherin could be used as surrogate markers to predict response of combined PEG IFN-alpha/RBV therapy, especially at week 12. However, an extended study including larger number of patients is needed for validation of these findings.Clinical trial No: NCT01758939.
"Most of them are chronically infected with risk to develop liver cirrhosis or hepatocellular carcinoma (HCC) . Combination therapy of pegylated interferon and ribavirin has been recommended and approved for patients with HCV infection . But treatment is costly and causes many side effects . "
[Show abstract][Hide abstract] ABSTRACT: Human leukocyte antigens class II play an important role in immune response against HCV. We investigated whether HLA class II alleles influence susceptibility to HCV infection and response to interferon therapy. HLA-DRB1 and -DQB1 loci were genotyped using PCR-SSO Luminex technology. According to our regimen, 41 (66%) of patients achieved sustained virological response to combined treatment of IFN and ribavirin. Frequencies of DQB1∗0313 allele and DRB1∗04-DRB1∗11, DQB1∗0204-DQB1∗0313, DQB1∗0309-DQB1∗0313, and DQB1∗0313-DQB1∗0319 haplotypes were significantly more frequent in nonresponders than in responders. In contrast, DQB1∗02, DQB1∗06, DRB1∗13, and DRB1∗15 alleles were significantly more frequent in responders than in nonresponders. Similarly, DRB1∗1301, DRB1∗1361, and DRB1∗1369 alleles and DRB1∗1301-DRB1∗1328, DRB1∗1301-DRB1∗1361, DRB1∗1301-DRB1∗1369, DRB1∗1328-DRB1∗1361, and DRB1∗1328-DRB1∗1369 haplotypes were significantly found only in responders. Some alleles and linkages showed significantly different distributions between patient and healthy groups. These alleles may be used as predictors for response to treatment or to susceptibility to HCV infection in the Egyptian population.
Mediators of Inflammation 03/2013; 2013:392746. DOI:10.1155/2013/392746 · 3.24 Impact Factor
"ODN 320 studied herein targets a highly conserved region in the otherwise highly variable HCV genome  (Figure 2F). Thus, ODN 320 may be suitable as antiviral agent against different strains of HCV, including those resistant to standard therapy, especially genotypes 1 and 4 [7,8]. Overall, this study underlines the potential of partially double-stranded ODNs as antiviral agents. "
[Show abstract][Hide abstract] ABSTRACT: Background
Persistent infection with hepatitis C virus (HCV) is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Standard therapy consists of a combination of interferon-alpha and ribavirin, but many patients respond poorly, especially those infected with HCV genotypes 1 and 4. Furthermore, standard therapy is associated with severe side-effects. Thus, alternative therapeutic approaches against HCV are needed.
Here, we studied the effect of a new class of antiviral agents against HCV, short, partially double-stranded oligodeoxynucleotides (ODNs), on viral replication. We targeted the 5’ nontranslated region (5’ NTR) of the HCV genome that has previously been shown as effective target for small interfering RNAs (siRNAs) in vitro. One of the investigated ODNs, ODN 320, significantly and efficiently reduced replication of HCV replicons in a sequence-, time- and dose-dependent manner. ODN 320 targets a genomic region highly conserved among different HCV genotypes and might thus be able to inhibit a broad range of genotypes and subtypes.
ODNs provide an additional approach for inhibition of HCV, might be superior to siRNAs in terms of stability and cellular delivery, and suitable against HCV resistant to standard therapy. This study underlines the potential of partially double-stranded ODNs as antiviral agents.
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