Egypt used to be on the top of the countries with heavy HCV burden. Treatment of HCV in Egypt has become one of the top national priorities since 2007. Egypt started a national treatment program intending to provide cure for Egyptian HCV-infected patients. Mass HCV treatment program had started using pegylated interferon and ribavirin between 2007 and 2014. Yet, with the development of highly effective direct-acting antivirals (DAAs) for HCV, elimination of viral hepatitis has become a real possibility. Egypt adopted a strategy that represents a model of care that could help other countries with high HCV prevalence rate in their battle against HCV Omran et al. [6].
The results of our study revealed that 95.1% of prevalent hemodialysis patients achieved SVR12 to the combination of ombitasvir/paritaprevir/ritonavir but treatment failure was observed in 4% of patients. Most of patients tolerated treatment; only 6 patients (12%) discontinued treatment due to side effects including severe anemia, fatigue, and GIT intolerance. In our study, three patients died during the treatment course. The most common side effects were anemia in 5 (10%) patients, requiring blood transfusion; gastrointestinal disturbance including nausea and vomiting in 7 patients (14%); severe fatigue in 3 (6%) patients; and itching in 2 (4%) patients.
The three patients that died during the course of treatment 2 patients had sudden death and 1 patient died due to cerebral hemorrhage despite normal platelet level and normal INR.
During the course of treatment, our study showed that patient had hemoglobin level drop, AST and ALT level improvement, increase at bilirubin level, and no change at albumin level, platelet level, total leukocyte count, and creatinine level.
Similar to our study, Liu et al. [7] investigated paritaprevir/ritonavir/ombitasvir for East-Asian non-cirrhotic hepatitis C virus patients receiving hemodialysis. Their study sample included 46 patients. The primary efficacy endpoint was sustained virologic response 12 weeks off-therapy (SVR12). The SVR12 rate was 100% (46 of 46 patients) like our study common side effects were hemoglobin drop (23%), pruritus (19.6%), and fatigue (15.2%). Their study results were different from the results of the present study as our study listed 6 patients that stopped treatment due to adverse effects but the other study reported that all patients tolerated treatment well.
In agreement with the present study, Lawitz et al. [8] investigated the efficacy and safety of ombitasvir/paritaprevir/ritonavir in patients with hepatitis C virus genotype 4 infection and advanced kidney disease. They selected 65 patients including 50 (76%) on dialysis and 15 (23%) had compensated cirrhosis. They reported that SVR12 rate was 95% (63/66); 3 patients discontinued treatment due to adverse events. Seventy-three percent (27/37) of patients receiving RBV had adverse events leading to RBV dose modification.
Another study, the results of which came similar to ours, is the study in which Mekky et al. [9] investigated the efficacy of ombitasvir/paritaprevir/ritonavir with ribavirin in the management of HCV genotype 4 and end-stage kidney disease study which enrolled 110 patients. As regards SVR12, it was 96% in HD and 91.4% in non-HD patients. Treatment failure was observed in 6 patients. There were no reported serious adverse events. Anemia was observed in 66.6% in HD group and in 31.4% in non-HD group.
The study by El Kassas et al. [10] observed high rates for the use of ombitasvir/paritaprevir/ritonavir containing regimens study which included 325 patients (age, 47.63 ± 12.63 years); SVR12 was attained by 100% of patients who received OBV/rPTV/RBV as assessed by modified intention to treat analysis. In concordance with the present study, they found that there was a significant improvement of baseline alanine aminotransferase and aspartate aminotransferase. The most common reported adverse effects were anemia, fatigue, and elevated indirect bilirubin four patients stopped treatment at week 4.
In contrast to our study, Said et al. [11] investigated ritonavir-boosted paritaprevir and ombitasvir plus ribavirin and 171 patients were included. All included patients reached the end of treatment with no treatment discontinuations. The overall end of treatment response was 100%; 16 patients required blood transfusions.
The study by Yaraş et al. [12] was different from the results of the present study as they reported that all 25 patients well tolerated the treatment regimen. Serious side effects causing treatment interruption were not observed. But their study agreed with the present study as they reported that the most frequent side effects were fatigue and itching. In accordance with the present results of the current study, a significant decrease in the level of serum alanine transaminase from 16.6 to 8.7 U/l after treatment was observed. This study enrolled 25 hemodialysis-dependent patients; they found that there was no difference in serum albumin levels. The mean serum bilirubin levels increased from 0.49 to 0.56 mg/dL after treatment.
To study the efficacy of paritaprevir/ritonavir/ombitasvir plus dasabuvir regimen in the treatment of chronic hepatitis C infection in patients with severe renal impairment and end-stage renal disease. Sperl et al. [13] enrolled 23 patients; SVR12 rate was 100%. Unlike our study, none of the patients presented with a significant decrease in hemoglobin level during the treatment period. The most frequent adverse events were nausea, hypotension, and diarrhea. Four patients presented with a serious adverse event unrelated to the antiviral drugs (salmonellosis, non-functional kidney graft rejection, early gastric cancer, renal cyst infection). Concomitant medication had to be modified with the treatment initiation in 10 out of 23 (43.5%) patients (calcium channel blockers, ACE inhibitors, statins, diuretics); four patients required further adjustment of antihypertensive drugs. Our study listed that no patients required dose adjustment of their medications.
In concordance with the present study, Atsukawa et al. [14] investigated the efficacy and safety of ombitasvir/paritaprevir/ritonavir and ribavirin for chronic hepatitis patients in 94 patients. In agreement with the current study, they found that SVR were 97.9%. Only two patients failed to achieve SVR. The median ALT levels decreased significantly after treatment. The hemoglobin levels decreased significantly during the treatment period, the most frequent adverse event was anemia (20.2%; 19/94 patients) and pruritus.
In agreement to our study, Liu et al. [15] assessed effectiveness and safety of paritaprevir/ritonavir/ombitasvir. One hundred and three patients were enrolled in the study. One patient prematurely discontinued treatment due to hepatic decompensation, 23 patients complained of fatigue, 23 patients had nausea, 14 had pruritus, and 9 patients had dropped hemoglobin level.
Abad et al. [16] observed sustained viral response to the combination of ombitasvir/paritaprevir/ritonavir. Thirty-five patients with genotypes 1 and 4 were treated with that DAA regimen. Sustained viral response was achieved in 100% of patients. Adverse effects were negligible, and no patient had to discontinue treatment. The most significant side effect was anemia, which led to a significant increase in the dose of erythropoiesis-stimulating agents. Anemia was more marked in patients receiving ribavirin. No patients required transfusions.
Atsukawa et al. [17] studied efficacy and safety of ombitasvir/paritaprevir/ritonavir in dialysis patients with chronic hepatitis C. The study enrolled 31 patients and end-of-treatment response SVR12 were 93.5%, while our study reported that SVR12 at hemodialysis group was 96.0% and at normal group was 100%. The incidence of adverse events was 35.5%. One discontinued the treatment. The most common adverse effect was pruritus (6.5%), while our study reported that 12% of patients stopped treatment and the most common adverse effect was hemoglobin drop.
Another study, the results of which came similar to ours, is the study in which Pockros et al. [18] studied the efficacy of direct-acting antiviral combination for patients with hepatitis C. Study sample included 20 patients completed 12 weeks of treatment. Eighteen of the 20 patients achieved SVR, one patient died after the end of the treatment (unrelated to the treatment) and 1 relapse accounted. Adverse events were primarily mild or moderate, and no patient discontinued treatment due to an adverse effect. Four patients experienced serious adverse effects all were considered unrelated to treatment. Ribavirin therapy was interrupted in 9 patients due to anemia. No blood transfusions were needed in contrast to our study in which patients needed blood transfusion. Most patients experienced side effects, the majority of which were mild or moderate in severity. No patient discontinued DAAs due to adverse effects. In agreement to our study, the most common side effects were anemia (45%), fatigue (35%), diarrhea (25%), and nausea (25%).
Arai et al. [19] studied efficacy and safety of ombitasvir/paritaprevir/ritonavir combination therapy for genotype 1b chronic hepatitis C patients complicated with chronic kidney disease; their study included 54 patients with impaired renal functions and 181 patients with normal renal functions. They concluded that only one patient among normal renal function group had increased in his serum creatinine level. This comes in agreement with our study that found that there is no effect of ombitasvir/paritaprevir/ritonavir on serum creatinine level during the course of treatment.