الفهرس 
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Abstract
This is a prospective observational study that described the effect of 12 weeks of daily oral sofosbuvir 400 mg plus daclatasvir 60 mg with or without ribavirin 1000–1200 mg for patients with CHC and early liver cirrhosis both interferon experienced and treatment naïve patients. It included Egyptian patients that fulfilled the inclusion criteria to receive DAAs and treated in AL Rajhy hospital, Asyut, Egypt, in the period between January 2018 to December 2019. The addition of RBV to treatment was kept for difficult to treat patients (cirrhotic and/or treatment experienced).
This study aimed to evaluate safety and efficacy of the sofosbuvir/daclatasvir treatment of chronic HCV GT-4 infection and to assess the occurrence and the prevalence of RAVs in patients with treatment failure and relapse after sofosbuvir and daclatasvir with identification of their types.
Eligibility criteria were adult patients with chronic HCV infection and HCV related liver cirrhosis with detected serum HCV RNA. Patients could have compensated cirrhosis child A & early B.
Diagnosis of cirrhosis in our study depended on the following laboratory: platelets < 100 x 103 /L, bilirubin < 2 mg/dL, albumin < 3.5 g/dL, and INR > 1.7. Imaging and endoscopic parameters: or esophageal varices,
The following patients were excluded from the study:
Decompensated cirrhosis (late Child B or C) or with history of decompensation, HIV or hepatitis B virus infection, chronic liver disease of non-HCV etiology (e.g.: autoimmune, vascular,…..), Bilirubin >2 mg/dl, Alanine and aspartate aminotransferase > 10 times ULN, Platelets < 50 x 103 /L, HCC.
We enrolled a total of 850 patients, all patients with chronic hepatitis C infection received dual therapy (n=548) while those with HCV related liver cirrhosis received triple therapy for 12 weeks (n=302). Follow up was done for 12weeks after last dose.
Regimens that were used in those patients were safe and tolerable, the most frequently recorded adverse events were headache (20%), fatigue (14%) and myalgia (5.2%). Diarrhea, abdominal pain and itching were experienced in 39 (4.6%), 34 (4%), and 17 (2%) patients, respectively. Insomnia was noticed in only 1.2% of patients. Patients were devided into two grops (CHC& liver cirrhosis). Both groups had no significant difference as regard adverse events with exception of significantly higher frequency of diarrhea among patients with liver cirrhosis (7.3%) vs. (3.1%).
There was a significant difference between both groups as regard SVR-12. The majority (91.2%) of patients achieved SVR-12 and 75 (8.8%) patients failed to achieve SVR-12.
In our study , as regards to the predictive factors associated with non-response to therapy were age more than 60 years, liver cirrhosis, FIB-4 more than 3.25 and APRI more than 1.45.
Because of financial issue, we couldn’t perform baseline RAVs among all the enrolled patients. So, we randomly select a sample of 100 patients with chronic HCV as representative to the studied patients. We found that 10 (10%) patients had RAVs before DAAs therapy.
At the end of therapy, we found that 75/850 (8.8%) patients from all enrolled patients failed to achieve SVR-12. RAVs were tested in those patients and found that only 1/75 (1.3%) from the non-responders had RAVs. Two non-responder (2 /75) patients have baseline RAVs.
Among naïve CHC genotype 4 patients naturally occurring resistance were encountered in 10 % of patient and the most frequent RAS were R270K, K304R, R231K, P300T, V252A. The occurrence of these RASs did not appear to have influenced therapeutic response after treatment, since most HCV are genotype 4-monoinfected patients had achieved SVR (>90%).
Out of patients tested for RAVs (100 at baseline & 75 non-responder), all patients had G4 while one patient has G1.
Conclusion
Treatment of CHC and early liver cirrhosis due to HCV infection with sofosbuvir/daclatasvir with or without ribavirin is generally safe and tolerable without significant side effects.
Sofosbuvir/daclatasvir combination is effective in treatment of CHC genotype 4 with SVR-12>90 %.
According to our test sample, RAVs testing is not routinely recommended before treatment of CHC as resistant variants occur naturally in patients with CHC in Egypt.
Most of these baseline substitutions did not seem to negatively impact treatment outcome, especially for GT 4 since most patients achieved SVR.