الفهرس 
LITERATURE REVIEWOnly 14 pages are availabe for public view
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Abstract
Combined Pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) treatment does not succeed to attain a sustained virological response (SVR) in about 20-50% of patients with chronic hepatitis C virus (HCV) infection. It has been found that Myxovirus resistance protein A (MxA) gene expression is a reliable and sensitive marker for the presence of exogenous type I interferons (IFNs) during IFN treatment. In addition, considering the involvement of anti-IFN-α binding antibodies (anti-IFN-α2a IgG Abs) and anti-IFN-α neutralizing antibodies (NAbs) on the non-response to treatment with PEG-IFN-α2a/RBV, Fifty-two PEG-IFN-α2a/RBV treated patients and sixteen healthy controls (without Hepatitis C) were enrolled in this study. This study is done after 12 weeks of treatment with combined therapy of PEG-IFN-α2a/RBV trying to find factors or markers for early detection of response to figure out the best treatment regimen for patients and reduce treatment costs. Our goal from this investigation was to examine the correlation between MxA gene expression, anti-IFN-α2a IgG Abs and NAbs and the early response to treatment, using both molecular and serological techniques. Then, the data were statistically analyzed.
Our results can be summarized in the following points:
1. Determination of HCV-RNA in plasma has been carried out for all patients at the beginning of treatment and at week12. Results showed that, 26 (50%) out of 52 patients were EVRs for treatment, while 26 (50%) patients were non-EVRs. No statistical significant difference between EVRs and non-EVRs as regard to age sub-categories (p=0.351). As regard to the gender, there was no statistical significant difference in gender distribution among EVRs and non-EVRs groups (p=0.578). There is a significant increase (p=0.012) in the abnormal level of AST (>38IU) in non-EVRs [19(73.1%)] when compared with the EVRs [10(38.5%)].
2. Quantification of MxA mRNA performed by real-time PCR showed a statistical significant elevation in the mean value of MxA mRNA in early virological responders (EVR) (4.10±1.54) when compared with both controls (3.19±0.89, p=0.026) and non-early virological responders (non-EVRs) (2.56±1.09, p=0.001).
3. Anti-IFN-α2a IgG Abs were assessed using indirect ELISA. The percentage of positivity of anti-IFN-α2a IgG antibodies in EVRs was 2/26 (7.7%) and in non-EVRs 4/26 (15.4%). There was no statistical significant difference between the mean values of anti-IFN-α2a IgG antibodies in EVRs (0.46±0.06) and non-EVRs (0.52±0.11), (p=0.321).
4. NAbs were distinguished by means of a neutralizing antibody assay that evaluated the neutralizing effects of serum samples against PEG-IFN-α2a. Serum samples were assessed for the presence of NAbs using rabbit polyclonal antihuman IFN-α2a as a positive control. In the 26 EVRs, no NAbs were detected. Of the 26 non-EVRs, two (7.7%) were positive for NAbs (p=0.149).
In general, this study ensured the importance of the detection of MxA expression as a factor for early assessing the probability of HCV genotype 4 patients to respond to treatment with PEG-IFN-α2a/RBV. Also, it showed that antibody production against IFN-α2a in patients getting treatment for chronic HCV infection is not a significant issue in early prediction of response and is not hindering the response to treatment.
CONCLUSION and RECOMMENDATION
The present study shows that:
1. Antibody production with PEG-IFNα2a in patients receiving treatment for chronic HCV infection is low and is not hampering with the treatment response. In this study single blood sample was taken from each patient after 3 months of initiation of the therapy, therefore it is possible that some cases might have been under reported as that might have produced low level antibodies at that time. It would be worthwhile to collect serial samples in few cases and see if values go up each month or are stable irrespective of the duration of therapy.
2. Also our data revealed that MxA protein expression is a sensitive biological marker for presence of exogenous type 1 IFN and the importance of the analysis of MxA expression during therapy which would be a practical approach to assess the individual molecular efficacy of the used combination PEG IFN-α2/RBV therapy, especially in genotype 4, which has not been previously investigated on the molecular level, and the probability to acheive a response for treatment.
3. Recommendation, studies using a larger number of patients would be very helpful in confirming our data.