The worldwide burden of HCV is estimated at 185 million out of which 12 million Egyptians suffer from HCV. Known to us is the morbidity of HCV as a leading cause of cirrhosis, hepatocellular carcinoma, and also known to us are the hepatorenal effects of HCV eventually leading to a higher rate of mortality among hemodialysis patients in specific. Hemodialysis has been identified as a separate risk factor for contracting HCV and taking into account the limited access of antiviral drugs due to the known toxicity of traditional HCV treatment on dialysis patients, new DAAs appeared as a better choice with ribavirin in those patients namely Qurevo ombitasvir/paritaprevir/ritonavir [9,10,11,12,13].
Our results revealed, regarding the efficacy, our SVR12 rate was 96% (48/50); 2 patients had virologic failure. This goes in line with the RUBY-I and RUBY-II trials presented at the meeting of the American Association for the Study of Liver Diseases (AASLD) held in Boston in November 2016, in which the SVR12 rate was 96% (46/48) in RUBY-I  and 94% (17/18) in RUBY-II by Gane et al. . Also, like the study in Japan by Atsukawa et al. , SVR12 rate was 96.8% (30/31), and like study in Egypt by Hanno et al. , SVR12 was also 96% (48/50). It was similar to a study in the USA by Lawitz et al. , the SVR12 rate was 95% (63/66), and in another study in Japan by Arai year 2018, SVR12 was 98.7%.
As regards the safety and adverse events, the most frequent were fatigue/asthenia in 44 patients (88%) and worsening anemia (Hb dropped to < 10 g/dl) in 42 patients (84%). GIT upset occurred in 10 patients (20%), sleep disorders in 8 patients (16%), decreased appetite in 8 patients (16%), respiratory distress in 6 patients (12%), and headache and dizziness in 6 patients (12%). Muscle spasms in 4 patients (8%). Itching (pruritis) occurred in 3 patients (6%). Two patients (4%) were non-responders to treatment, and another 2 (4%) were relapsers. Death was reported in 4 patients (8%), post-treatment probably unrelated to treatment, due to myocardial infarction, pulmonary edema, severe hypotension on hemodialysis sessions, and shock due to blood loss in retroperitoneal hematoma following peritoneal dialysis. Hepatic decompensation, hypersensitivity (angioedema), teratogenicity, and drug interactions did not occur in any patient (0%). Other events occurred in 11 patients (22%)% during therapy, not yet proved to be related or not to the drug. They were parenchymal liver changes in ultrasound at the end of therapy, after being normal before therapy (in 3 patients), thrombocytopenia, increased alkaline phosphatase, hiccough, deterioration of hypertension, urinary tract infection, lower limb cellulitis, vaginal bleeding, and chest infection (in 1 patient each). These results go in line with the RUBY-I trial  and Lawitz et al.  study in the USA, in which anemia was the most common adverse event. But, unlike the study of Atsukawa et al.  in Japan, which used a ribavirin-free regimen, and Hanno et al.  in Egypt, which enrolled different CKD stages (2–5) in which pruritis was the most common adverse event.
As regards follow-up CBC, liver enzymes, and liver functions in weeks 4, 8, and 12, we found that HGB levels decrease, total and indirect bilirubin increase due to ribavirin (RBV)-associated hemolysis , and AST, ALT, and INR levels decrease. This is in agreement with Hanno et al.  study in Egypt.
As regards anemia being the most common adverse event, several studies including ours confirm 2 observations. First, anemia during HCV treatment occurs higher with more advanced renal failure (more in CKD 5 dialysis patients than CKD 2–5 than non-CKD) shown by Osinusi et al. . Second, it occurs in the majority of the studies with ribavirin including regimens. This was obvious in our study which included both advanced renal failure, ESRD patients on regular hemodialysis, and ribavirin including regimen.
To overcome anemia in ESRD receiving HCV therapy, ribavirin dose is 200 mg/day (typically starting at 200 mg three times weekly and titrating up to 200 mg/day as tolerated). Ribavirin should be discontinued if the hemoglobin level decreases by more than 2 g/dl despite the use of erythropoietin according to (AASLD) guidelines . SVR12 rate in our study was achieved in 100% of patients who had to stop or modify RBV dose; this means that RBV absence did not affect the SVR12 in these patients. This leads us to think of RBV-free regimens in ESRD patients as a safer option of treatment to avoid severe hemolytic anemia with ribavirin that occurs with these patients despite various anemia managements during therapy.
The current guidelines recommend two ribavirin-free regimens for patients with HCV infection and stage 4 or 5 CKD, elbasvir/grazoprevir, which is approved for the treatment of patients with GT1 or 4 infection, and glecaprevir/pibrentasvir, which has pan-genotypic activity. Both show high efficacy (SVR12) with no anemia as adverse event in ESRD. For this reason, the regimen used in our study ombitasvir/paritaprevir/ritonavir and ribavirin would be considered to be alternatives to the 2 recommended regimens . However, these 2 regimens are not yet available in Egypt.
There were several limitations in our study. First, we could not study the effect of our drug on CKD staging because our patients were all ESRD, CKD 5 on regular hemodialysis. Second, ribavirin caused hemolytic anemia, which was an inconvenient adverse event. Third, only 4 patients had to stop or modify RBV which was a small number. So, we could not draw a firm conclusion about RBV-free ombitasvir/paritaprevir/ritonavir regimen as being effective alone in the treatment of HCV. Fourth, our study had 2 virologic failures and 2 relapses. We correlated between them and RBV dose modification and also HCV viral load but there was no statistically significant relation. It was difficult to know the exact causes of failure of treatment and relapse due to a small number of them. However, other studies attribute the cause to resistance-associated substitutions in the NS3/4A region before treatment. For instance, Q80K shows a threefold resistance to paritaprevir (NS3/4A protease inhibitor). The detection rate of pre-existing D168 substitution is also found . Fifth, we did not do genotyping on the patients assuming that genotype 4 is the most common variant of HCV throughout Egypt and represents more than 90% of HCV isolates from Egyptian patients . So, we could not study the effect of our drug in different HCV genotypes (1–6) However, it is obvious that our drug shows high efficacy in genotype 4 assuming that most HCV Egyptians have genotype 4.