HCV infection is considered a major clinical burden in β thalassemia patients. The prevalence of HCV is much higher among patients with beta-thalassemia, as these patients constitute a 4 high-risk group. A systematic review based on the literature database showed that the anti-HCV antibody among β thalassemia patients has been estimated at 18%, 45%, 63%, and 69% in Iran, Pakistan, Saudi Arabia, and Egypt, respectively . Approximately 70–80% of those patients will progress to CHC and up to 20% will go on to cirrhosis . It is also known that HCV infection is a risk factor for HCC, which has been considered as the second common cause of mortality in this population .
Herein, our study provides further proof that oral DAAs are highly effective and tolerable by β thalassemia patients with CHC. All enrolled patients achieved SVR at 12 weeks and at 24 weeks. Compared to the Italian cohort  and the Greek cohort , SVR was achieved in most of the patients (98% and 90%, respectively). Both studies included 57.1% vs. 78.7% and previously treated patients 42.9% vs. 75%. The achievement of 100% SVR in our study could be explained by the fact that all enrolled patients were treatment naïve and had no cirrhosis as the median FIB-4 score was 0.52. However, those patients should be monitored for the possibility of reinfection.
Hezode et al.  published a trial using a fixed combination of elbasvir and grazoprevir in patients with congenital blood disorders and CHC, including β thalassemic patients. Forty β thalassemia major patients received treatment for 12 weeks, and SVR was achieved in 97.6% of them. This study showed that treatment was well-tolerated by the patients, and hemoglobin levels were not affected by treatment. The most frequently reported side effects in this study were, e.g., headache, fatigue, nausea, and asthenia. However, this combination is not currently available in Egypt.
Also, in a case series of four β thalassemia patients with CHC associated with advanced hepatic fibrosis, treated with the LDV/SOF combination for 12 weeks, all patients achieved SVR with accepted drug safety and tolerability. The only reported adverse events were mild asthenia and headache. There were no changes in chelation therapy or transfusion requirements during the treatment period. Similar results were presented by Mangia et al. [20, 21].
In the present study, there were no major adverse events, and no discontinuation of treatment was reported. Only one case required temporary treatment discontinuation due to acute kidney injury after the prolonged use of NSAIDs then resumed DAAs after the decline of serum creatinine to the normal value. Mild symptoms occurred in approximately 22.72% of the patients. The most common side effects were fatigue (18%), anemia (13.63%), and headache (4.5%). This is in accordance with the published data from certain clinical trials [18, 22]. These side effects were more common among patients receiving SOF plus DCV than in patients receiving SOF plus LDV; however, this difference in the rates of occurrence of side effects was not statistically significant (p = 0.58). Also, no drug-drug interactions were observed.
There was a significant improvement of mean ALT values and a significant decrease in serum bilirubin after treatment. On the other hand, no statistically significant difference in the hemoglobin level, platelet count, and WBCs count were found before and after DAAs. Only 12 patients had increased blood transfusion requirements, despite a non-significant difference being noticed between the mean HB level before and after DAAs. The dose and type of iron-chelating therapy did not require any modifications during the treatment course.
A high hepatic iron concentration was proposed as a negative predictor of response to DAAs in different ethnic populations. There was no consensus on whether iron accumulation in the sinusoidal cells or hepatocytes and portal track macrophages was more significant for poor response to treatment .
Assessment of hepatic iron concentration was limited and mainly based on serum ferritin levels and non-invasive techniques without liver histology and the data of post-treatment assessment of hepatic iron overload were not obtainable during the study. So, we need further studies with larger samples and newer DAA combinations.