الفهرس 
Acknowledgement
Natural History of HCV Recurrence after LTOnly 14 pages are availabe for public view
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Abstract
The major indication for LT in North America and Western Europe is liver disease resulting from chronic infection with HCV (Crespo et al., 2012). In Egypt, HCV infection is a major health concern (Amer and Marwan, 2016). The prevalence of HCV among the 15−59 year-age group is estimated to be 10% (the highest prevalence in the world)(Kandeel et al., 2017). The high prevalence of HCV related chronic liver diseases has led to increasing numbers of Egyptian patientssuffering from ESLD, necessitating LT; The vast majority of indications (64%) were HCV related (Amer and Marwan, 2016).
For patients with detectable serum levels of HCV RNA at the time of transplantation, recurrence of HCV infection is immediate and universal (Wiesner et al., 2003). Recurrent HCV infection after transplantation is generally aggressive, and progression to cirrhosis and decompensation is more rapid than in patients with HCV who have not been transplanted(Berenguer and Schuppan, 2013).
Treatment options for patients with recurrent HCV after transplantation were limited. For patients with severe recurrence, IFN based regimens are difficult to tolerate and have disappointing efficacy with hard-to-manage drug interactions(Lens et al., 2014). Triple-therapy regimens with protease inhibitors have been shown to improve efficacy, but exacerbate the side effects of treatment and are complicated to be administered with immunosuppressive drugs (Burton and Everson, 2013).
Therefore, there is a great need for a more-potent as well as more-tolerable regimen without drug interactions for LT recipients with recurrent HCV. SOF is a potent inhibitor of the HCV NS5B polymerase. SOF has been approved in combination with RBV, with or without Peg-IFN, for treatment of CHC genotypes 1-6 (Jacobson et al., 2013).
Real-life data regarding the safety profile, tolerability and effectiveness of SOF based regimens in the organ transplant recipients are limited, especially in early post-transplantation period. Our single arm prospective cohort emerged to evaluate the efficacy and the tolerability of a combination of 400mg SOF and median dose of 800 mg RBV for 24 weeks for post-transplant patients with documented recurrent hepatitis C who were followed for another 12 weeks post-treatment.
from August 2014 till January 2016, sixty patients were enrolled, 78.3% were male, 70% had genotype 1 and 61.7% received previous HCV treatment. At baseline, 21 patients (35%) had severe fibrosis according to Ishak score. The median time interval from LT was 51 months (5-284), immunosuppressive therapy was Tac based in 78.4%. The median baseline HCV-RNA was 2.341.172 IU/mL (770-52.330.800 IU/mL).
The combination of SOF and RBV in the treatment of recurrent HCV infection after liver transplantation was safe and tolerated regimen with no recorded serious side effects or deaths directly related to drugs used in our study. Anemia was the most frequent event (38.3%) which was attributed to the hemolytic effect of RBV and asthenia as the second one (16.7%), while dyspnea and fatigue presented in about 6-8%.
There was no significant interaction between SOF and Tac which was the backbone of immunosuppression in our study. We reported no considerable changes in the level or the dose of Tac during the course of the therapy.
SOF and RBV were fairly effective regimen in treatment of recurrent HCV infection after transplantation. In the present cohort, we concluded that the factors affecting SVR, are the presence of baseline HE, the degree of hepatic fibrosis, pre-treatment LS values; being measured by Fibroscanand the previous antiviral therapy for HCV post-transplant.
There was significant decrease in liver enzymes; ALT, AST and ALP towards the normal values, associated with increase in albumin value post-treatment. Treatment of recurrent HCV post-transplant results in marked clinical improvement as we noticed disappearance of ascites in most of the patients that involved in our study with subsequent improvement in Child-Pugh score. Furthermore, we reported significant decrease in the score of LS post-treatment as measured by Fibroscan in all patients of the study especially in patients who achieved SVR in comparison to those who did not achieve. Also, the current study showed that non-invasive biomarkers of liver fibrosis as APRI and FIB-4 scores were significantly improved in those patients who achieved SVR. Although in patients who didn’t achieved SVR, APRI and FIB-4 were decreased, yet this decrease had no significant changes.
There was no significant change in total lymphocytic count and lymphocytic subpopulations before and after therapy except for NK count which was significantly increased in the patients who achieved SVR.