الفهرس 
Acknowledgement
Hepatitis C Genotypes and QuasispeciesOnly 14 pages are availabe for public view
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Abstract
Hepatitis C virus (HCV) is a global health problem. It is a leading cause of cirrhosis, hepatocellular carcinoma (HCC), liver transplantation and liver-related death worldwide. Gower et al. (2014) estimated that 80 million persons were living with HCV infection.
Until 2011, the combination of PEG-IFN-α and RBV for 24 or 48 weeks was the approved treatment for chronic hepatitis C. With this regimen, patients infected with HCV genotype 1 had SVR rates of approximately 50% while higher SVR rates were achieved in patients infected with HCV genotypes 2, 3, 5 and 6 and intermediate SVR rates were achieved in those with HCV genotype 4 (Antaki et al., 2010).
Clinical trials have highlighted the safety and efficacy of newly introduced SOF-based regimens, leading to the rapid approval of this therapy. FDA (2013) approved SOF for treatment of CHC infection genotypes 1, 2, 3 and 4 as part of combination antiviral regimen. However, additional data are still needed to optimize both combination therapies’ efficacy and duration in some categories of patients (D’Ambrosio et al., 2015).
The present study aimed to assess the safety of these sofosbuvir (SOF) containing regimens and their efficacy on virological response {end treatment and 3 months after end treatment (sustained virological response)} among HCV related liver cirrhosis. Also, to evaluate the efficacy of these treatment regimens for one year after the end of treatment as well as to evaluate the effect of sustained virological response on the clinical outcomes and liver fibrosis.
This prospective study was conducted on 300 treatment-naive patients with compensated HCV related liver cirrhosis. All patients were recruited from National Viral Hepatitis Treatment Center in Assiut and they were selected according the selection criteria determined by the National Committee for Control of Viral Hepatitis (NCCVH).
All patients were categorized into 3 Groups, each group included 100 patients, group 1 received triple therapy (Sofosbuvir 400 mg/day, PEG-IFN-α2a 180 mcg/week and weight based Ribavirin daily for three months), group 2 received dual therapy (Sofosbuvir 400 mg/day and weight based Ribavirin daily for six months) and group 3 received Sofosbuvir 400 mg/day, Daclatasvir 60 mg/day and Ribavirin (at initial dose of 600 mg/day with a step wise titration upwards) for three months.
Complete blood count and liver function tests were ordered at baseline, monthly during treatment duration, at the end of treatment and during follow-up duration. While abdominal ultrasound and AFP were ordered at baseline, end of treatment then every 6 months for one year after the end of treatment.
HCV RNA level was tested during treatment at week 4, week 12 for all three studied Groups and also at week 24 for group 2. For those who had achieved end treatment response, HCV RNA level was tested at 3 months after end of treatment and for those who achieved SVR12, HCV RNA level was checked after 9 months (SVR48).
Calculation of MELD score and non-invasive indirect markers of fibrosis as APRI and FIB-4 scores was done at baseline, end of treatment and at 3 months after end of treatment for those who achieved end treatment response also at 3 months and 9 months after achieving SVR12.
Fibroscan examination was done for 20 patients in group 1, 20 patients in group 2 and 24 patients in group 3 at the baseline and at 1 year after end of treatment (SVR48).
The sustained virological response (SVR12) rate was 83% in group 1, 75% in group 2 and 96% in group 3. The relapse rate was 16% in group 1, 23% in group 2 and 4% in group 3. All patients who achieved SVR12, have undetectable HCV RNA by PCR at the end of follow-up duration (SVR48).
group 3 had significantly higher SVR12 rate when compared to group 1 and 2 (P value < 0.05), and the least treatment failure rate and relapse rate.
In patients who achieved sustained virological response, there was improvement in platelet count, liver function parameters, AFP, MELD, Child-Pugh score and indirect fibrosis markers (APRI and FIB4) at the time of SVR12 and at the end of follow-up (48 weeks after end of treatment) in comparison to baseline values. Also, liver stiffness measurements improved at the end of follow-up compared to baseline measurements.
152 patients of the three studied Groups (50.6%) suffered from minor side effects which were managed during treatment and only 2 patients in our study stopped RBV (one patient in group 2 and the other in group 3) because of DROP in Hb level to less than 8.5 g/dl.
Sofosbuvir based regimens were effective in treatment of HCV related liver cirrhosis and had efficacy higher than traditional regimen (IFN/RBV). SOF/DAC/RBV was the most efficacious and tolerable treatment regimen as it was associated with the highest SVR rate and the least reported adverse effects. With the further development of sofosbuvir based regimens, the hope to increase efficacy and safety will be raised in cirrhotic patients and special patient Groups.