الفهرس 
AbstractOnly 14 pages are availabe for public view
 |  | from | 244 |  |  |
| | | from | 244 | | |
Abstract
Introduction:
The discovery of direct-acting antiviral agents (DAA) is an outstanding achievement of modern medicine in the current century. The current study aimed to explore the effectiveness and safety of sofosbuvir (SOF) with other combination therapies of DAA in chronic hepatitis C (CHC) genotype (GT) 4 patients in Egypt.
Material and methods:
A number of 1455 treatment-naïve and treatment-experienced adults aged 18 – 70 years (998 male and 453 female) with chronic HCV-GT4 infection were allocated into six groups based on the type of regimen used. Patients in group 1 received daily oral SOF, RBV (the dose modified according to patient tolerability) plus Peg-INFα-2 once weekly for 12 weeks. In group 2, patients were treated orally with SOF plus daily oral weight-based RBV (24 weeks). Patients in group 3 were treated orally with SOF plus daily oral SMV (12 weeks).on the other hand, patients in group 4 were classified into two subgroups: subgroup 1 (easy to treat) was treated with a dual therapy of SOF/DCV daily for 12 weeks and subgroup 2 (difficult to treat) was treated with a triple therapy of SOF/DCV/RBV daily for 12 weeks. Patients in group 5 were patients were treated orally with SOF plus a fixed-dose combination of OBV/PTV/r + RBV, which was administered orally based on the patients’ tolerability. While patients in group 6 were treated with SOF/ DCV/SMV plus RBV for 12 weeks in Egyptian patients infected with chronic HCV GT4 who failed prior DAA treatments. Efficacy and safety of the treatments were estimated, and baseline characters associated with the sustained virological response at 12 weeks post-treatment (SVR12) were investigated.
Results:
In group 1, sustained virological response 12 weeks after the end of treatment was achieved by 88% (87/99) of all patients, by 93% (55/59) of naive patients and by 80% (32/40) of experienced patients. Otherwise, the most common adverse events observed during the study included headache, nausea, fatigue, dyspnea, influenza-like illness, anemia, and leukopenia.
In the patients who received SOF/RBV therapy for 24 weeks, a sustained virological response (SVR12) was achieved by 89% (90/101) of all patients, 92% (49/53) of naïve patients and 85% (41/48) of experienced patients. In the SOF/SMV group, the SVR12 rate was 92% (92/100) for overall patients, 93% (70/75) of naïve patients and 88% (22/25) of experienced patients. Adverse events (AEs) were reported in 70% of patients in the SOF/RBV group and 42% of patients in the SOF/SMV group. The most common AEs in both groups were fatigue, headache, nausea, and dyspnea.
Among the patient’s cohort in group 4, SVR12 was achieved by 94% (891/946) in the overall patients, by 95% (718/758) in the easy-to-treat group, and by 92% (173/188) in the difficult-to-treat group. The most common adverse events recorded were fatigue, headache, nausea, asthenia, and gastrointestinal troubles. No patient discontinued treatment due to severe adverse events.
Among experienced patients treated with SOF/OBV/PTV/r+RBV, SVR12 rates achieved 97% in overall patients (109/113); SVR12 rates achieved 98% (81/83) of non-cirrhotic patients and achieved 93% (28/30) of cirrhotic patients. Additionally, SOF/DCV/SMV +RBV therapy achieved SVR12 of 97% in overall patients (89/92); SVR12 rates achieved 99% (70/71) of non-cirrhotic patients and achieved 91% (19/21) of cirrhotic patients. Otherwise, the most common adverse events for the two treated groups were fatigue, headache, insomnia, nausea and dyspnea.
Conclusions:
SOF combination-based therapies were considered promising choice regimens for chronic HCV infection. The present findings suggest that the combination of the SOF with other regimens of DAA (with or without RBV) exhibited high effectiveness, was well tolerated in the treatment of chronic HCV GT 4, and revealed itself as a better option for patients with advanced liver disease, making the eradication of HCV a more realistic target to achieve.
Key words:
Egyptian patients, chronic hepatitis C, HCV genotype 4, Sofosbuvir, Peg-interferon α-2, Ribavirin, Simeprevir, Daclatasvir, Ombitasvir, Paritaprevir.