الفهرس 
• Acknowledgements •Only 14 pages are availabe for public view
 |  | from | 167 |  |  |
| | | from | 167 | | |
Abstract
HCV infection remains a major global public health burden with
an estimated 71 million persons chronically infected. The prevalence of chronic HCV infection is estimated to be 0.9-1.3% in the US, affecting 2.9-4.1 million Americans. In China, the prevalence of chronic HCV infection is estimated at 0.7-1.3%, representing around 9.8-18.2 million people. Egypt had the largest HCV epidemic worldwide as the prevalence of HCV reached 14.7% before initiation of the National Program for Treatment of CHC.
Roughly 10-20% of persons with chronic HCV infection will
develop cirrhosis after 20-30 years of infection. Once cirrhosis
has developed, the annual incidence of HCC has been reported to be 1-5% and hepatic decompensation to be 3-6%.
The DAAs are nowadays considered the cornerstone of HCV management. The goal of antiviral therapy is to eradicate HCV RNA, which is predicted by achieving SVR. Achieving SVR was associated with decreasing liver-related deaths, hepatocellular carcinoma rates and liver-related complications, even among those patients with advanced liver fibrosis.
Previous studies demonstrate that lower rates of comorbidities, lower HCV viral loads, ALT, AST levels, and FIB-4 score were predictors of SVR12 in interferon based regimen. Patients with younger age, less fibrotic liver (FIB-4 score <1.45) and lower levels of HCV initial viral load (<800K IU/ML) were more likely to achieve treatment success (SVR12). Factors such as diabetes, HCV viral load >6MM IU/ML, FIB-4 score >3.25 and DAAs plus ribavirin were independently associated with treatment failure. However, little is known about the predictors of SVR12 to DAAs.
Chemokine (C-X-C motif) ligand 10 (CXCL10) and other CXCR3 chemokines are involved in the pathogenesis of acute and chronic hepatitis C virus infection. CXCL10 in plasma is mirrored by intrahepatic CXCL10 mRNA, and both strikingly predict the first days of elimination of HCV RNA (“first phase decline”) during therapy for all HCV genotypes.
CXCL10 below 150 pg/mL independently predicted the first phase viral decline and rapid virological response, which in turn independently predicted SVR. DAA agents-mediated clearance of HCV is associated with the loss of intrahepatic immune activation by IFN-α, associated by decreased levels of CXCL10.
The main aims of our study were:
1) To assess the pattern of response in chronic HCV infected patients treated with sofosbuvir 400 mg plus daclatasvir 60 mg with or without ribavirin for 12 weeks.
2) To study the predictors of non-response to this regimen in the non-responder.
3) To study the predictors of non-response to this regimen in relapsed groups.
Our study was conducted on 506 CHC infected patients who attended the Tropical Medicine and Gastroenterology outpatient clinic in Sohag University Hospital and advised to receive anti HCV treatment in a specialized center. The study protocol was approved by Sohag Faculty of Medicine Ethical Committee. All participants gave a written consent before participating in the study.
Before starting treatment, patients were categorized into CHC infected patients with non-cirrhotic liver and CHC infected patients with liver cirrhosis (compensated or decompensated).
The cirrhotic patients were classified according to Child-Pugh score.
After completing the course of treatment, all patients were followed up for 6 months and categorized into patients with sustained virological response and those with non-sustained virological response.
Pretreatment abdominal ultrasonography, fibroscan, alpha fetoprotein (AFP) and random blood sugar were performed to all patients. Hepatitis C virus RNA were performed pretreatment, at the end of the treatment, post treatment week 12, and post treatment week 24. Liver function tests and complete blood count (CBC) were performed pretreatment, treatment week 4, 8, 12. Serum sample were taken pretreatment to measure C-X-C motif chemokine10 (CXCL10) by ELIZA.
Our study revealed that rate of SVR was 98.2%. The response rate was 24.5% in cirrhotics and 75.5% in noncirrhotics. Presence of liver cirrhosis and the need for receiving triple therapy were the main factors that predicted relapse in univariate analysis. However this result couldn’t be confirmed in multivariate analysis. Pretreatment CXCL10 value showed no statistically significant difference between responders and relapsers.
Conclusion:
With well tolerated DAAs, response rates in patients with
cirrhosis remains lower than in noncirrhotics. Lower Child-Pugh score and use of DAA regimens without ribavirin were significant predictors of achieving SVR.
Recommendations:
We recommend further studies conducted on large number of decompensated patients.