الفهرس 
ContentsOnly 14 pages are availabe for public view
 |  | from | 161 |  |  |
| | | from | 161 | | |
Abstract
Since HCV infection is one of the leading causes of liver cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation globally, those patients with HCV are in need for effective antiviral therapy to halt the progression to these complications and hence reduce mortality (Shawkat et al., 2015; Elgharably et al., 2017). Real-life data regarding the safety profile, tolerability and effectiveness of SMV/SOF combination therapy in Egyptian patients are limited. Our prospective, open label, single arm study was emerged to evaluate the efficacy and the tolerability of a combination of 400mg SOF and 150 mg SMV for 12 weeks and were followed up for another 72 weeks post-treatment. from 1st of December 2015 till 30th of November 2017, 59 patients were enrolled, 69.5% were male, 91.5% naïve, 8.5% INF experienced and all of them had genotype 4. At baseline, according to investigation with Fibroscan, the liver fibrosis stage was F4 in 17 patients (28.8%), F3 in 11 patients (18.6%), F2 in 17 patients (28.8%), F1 in 4 patients (6.8%) and F0 in 10 patients (16.9%).All 59 patients were infected with only HCV genotype 4a (100%). To our knowledge, this is the first study that reports the prevalence of baseline NS34A RASs in patients treated with DAAs in routine clinical practice in Upper Egypt and we did not find any baseline RASs in NS34A region of HCV RNA (0%). In the present cohort, we concluded that the efficacy of SMV/SOF combination therapy in achieving SVR was 96.6% and in the improvement of liver fibrosis, according to investigation of liver stiffness by Fibroscan was (80.9%).There was a significant decrease in liver enzymes; ALT and AST towards the normal values. Furthermore, we reported significant improvement in APRI score and Fib-4 index. RASs testing of NS34A region in the two patients who did not achieve SVR revealed the presence of emerging Q80K RAS in one patient (50%).Simeprevir/Sofosbuvir combination therapy was highly effective and safe in treating naïve and INF experienced chronic HCV infected patients either without cirrhosis or with compensated cirrhosis with no recorded serious side effects or deaths directly related to drugs used in our study. Raised bilirubin >1.2 mg was the most frequent event (54.2%) (71.8% <2 mg). Less frequent side effects were noticed including dermatological side effects, headache, bleeding per gum, and fatigue. All side effects were tolerable and reversible. The conclusions to be withdrawn from this study are: All 59 patients were infected with only HCV genotype 4. Absence of baseline RASs in NS34A region of HCV RNA. Simeprevir/Sofosbuvir combination therapy was highly effective and safe in treating naïve and INF experienced chronic HCV infected patients either without cirrhosis or with compensated cirrhosis. Adverse effects of SMV/SOF combination therapy, with special consideration of dermatological side effects and raised bilirubin, were reversible. Liver stiffness and the other laboratory non-invasive markers of liver fibrosis (Fib4 and APRI score), improved significantly after treating CHC patients with SMV/SOF combination therapy and achieving SVR. Emerging Q80K RAS was found in one patient among the two patients who did not achieve SVR12. Although the combination of SMV and SOF was fairly effective in treating chronic HCV infection, it is not recommended now by the latest EASL recommendations in 2018 due to the approval of new regimens of novel DAAs with higher efficacy and safety profile. We can reassure chronic HCV patients either without cirrhosis or with compensated cirrhosis that their liver state can improve after achieving SVR. All 59 patients were infected with only HCV genotype 4 so, to investigate for HCV genotype in Upper Egypt might not be needed in naïve and INF experienced patients. Also, in Upper Egypt, to investigate for RASs in NS34A region before starting treatment with NS34A inhibitors may not be needed in naïve and INF experienced patients, because we did not find any baseline RASs in our study group. Patients who did not achieve SVR to SMV/SOF combination therapy; retreating them with another NS34A inhibitor may not be recommended because we found Q80K RAS in one among of the two relapsed patients, and RAS testing would be useful before retreatment with another NS34A inhibitor. Extended duration of follow up is needed to detect long-term impact of HCV eradication on the improvement of liver fibrosis.