الفهرس 
Introduction & Aim of the workOnly 14 pages are availabe for public view
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Abstract
Introduction:
Hepatitis C virus infection is considered a great challenge in Egypt. It has been estimated that 10% of the Egyptian population between 15 and 59 years of age are chronically infected with HCV. The use of DAAs for the treatment of HCV patients provides a good chance of achieving sustained virological response. The SVR rate with their use is approximately ≥ 95 %.
Dysregulated immune responses towards HCV were observed. These dysreulated responses were linked to poor treatment response in the previously used interferone based regimens. Of the most important previously studied immunological markers is IP-10 (CXCL10).
Aim of the study:
-Identification of clinical, laboratory, imaging or immunological predictors of virological response to DAAs.
-Ellucidation the influence of HCV-induced immune dysfunction on virological response to DAAs .
Patients and methods:
This study included 200 chronic hepatitis C patients receiving DAAs treatment at the outpatient clinic of Minia university liver center. After written consents had been taken, they were classified into 2 groups: group one; included HCV cirrhotic patients, group two; included CHC patients without liver cirrhosis.
After full history taking and clinical examination had been done, the following investigations were done: CBC, LFTs, ALT, AST, serum creatinine, AFP, HCV RNA by PCR, HBA1c, CXCL10, IL12, flowcytometry to evaluate PBMN and identify NK cells and their subset by their expression of CD56 and CD16, and abdominal sonography.
All patients received a combination of Sofosbuvir plus Daclatasvir with the addition of ribavirin in cirrhotic patients, for 3 months.
By the end of treatment; all investigations were re-done.
3 month after the end of treatment; HCV RNA PCR was done to evaluate response using SVR12.
Results:
There was a statistically significant difference between means of age of both groups as it was 41.4 ± 10.9 for group I, while it was 63.2 ± 8.1 for group II. Also significant differences were present between platelets counts and albumin levels of both groups. Moreover, a statistically significant difference was found between CXCL10 levels of both groups as it was 148 (144-154) for group I, while it was 253 (247-260) for group II (P < 0.001), the percentage of CD56-16+ NK cells was higher in group II.
Three months after the end of treatment, SVR12 was evaluated and revealed the following: group I showed a significant higher rate of response than group II, as SVR12 was achieved in 130 (96.3 %) patients of group I, while it was achieved in 55 (84.6 %) patients of group II.
Responders and non-responders were compared regarding demographic characteristics, pre-treatment laboratory values, imaging and revealed there were significant differences between age, albumin levels, platelets counts and presence of splenomegaly of responders and non-responders. Also non-responders showed a higher pretreatment level of CXCL10 and a higher pretreatment percentage of the dysfunctional NK subset.
Conclusion:
The predictor factors of response to DAA treatment are advanced age, low pretreatment platelet count, high pretreatment serum CXCL10 level, and high baseline frequency of the dysfunctional CD56- 16+ NK subset. Thus, all these factors should be considered prior to the initiation of a sofosbuvir/daclatasvir regimen.