Real-life results of triple therapy with the combination of sofosbuvir-pegylated interferon-ribavirin for Egyptian patients with hepatitis C Prof. Gamal Esmat Prof. Hepatology & Vice President of Cairo University, Egypt Member of WHO Strategic Committee for Viral Hepatitis www.gamalesmat.com
G Esmat 1, W Elakel 1, M Elserafy 1, A Yosry 1, A Omar 1, W Doss 1, I Waked 2, MH Elsayed 3, Z Mahran 3, M Makhlouf 3, Y Elshazly 3, N Elgarem 1, A Gaballa 1, K Kabil 4, M Hassany 5 1 Cairo University, Cairo, Egypt, 2 National Liver Institution, Menoufia, Egypt, 3 Ain Shams University, Cairo, Egypt, 4 National Committee for Control of Viral Hepatitis, Cairo, Egypt, 5 National Hepatology and Tropical Medicine Research, Cairo, Egypt
Global prevalence &genotype distribution
Prevalence of HCV in Egypt Socioeconomic characteristic Urban-rural residence Urban Rural Place of residence Urban Governorates Lower Egypt Urban Rural Upper Egypt Urban Rural Frontier Governorates Education No education Some primary Primary complete/some secondary Secondary complete/higher Wealth quintile Lowest Second Middle Fourth Highest HCV antibody positive, % 10.3 18.0 9.5 17.5 11.8 19.3 14.7 10.9 16.4 3.8 24.0 20.4 11.5 10.5 18.6 17.1 16.4 11.6 10.2 Total 14.7 El-Zanaty F & Way A. Egypt Demographic & Health Survey 2008
National Survey (DHS) 2015 (1-59 years) 2015(1-59 Y) HCV Ab 6.3% HCV PCR 4.4%
Egypt faces the largest burden of HCV infection in the world, and infection is predominantly with genotype 4. Triple therapy with sofosbuvir (SOF), pegylated interferon (PEG) and ribavirin (RBV) has shown very high sustained virological response (SVR) rates in clinical trials that included HCV-genotype 4 patients. Its introduction in late 2014 in a national treatment program marked the beginning of a new era in HCV therapy in Egypt. The real-life results of this therapy for HCV genotype 4 is not known.
SVR12 (%) Resource-limited settings: the Egyptian example Gilead access program 100 reduced 100 cost drastically National treatment 88 83 program started October 80 2014.by SOF based therapy 60 SOF-PEG-RBV 12 40wks for IFN eligible patients (triple therapy) 20 SOF-RBV 24 weeks for IFN-ineligible patients(dual therapy) 0 DCV PEG-RBV 24-48 wks SMV PEG-RBV Naiive 12+24 wks SMV PEG-RBV Experienced 12+48 wks 96 SOF PEG-RBV 12 wks 100 SOF RBV 24-wks Naiive 87 SOF RBV 24wks Experienced 738,000 registered for evaluation 95 Of them 202521 100 were 100 evaluated 100 90.9 40,000 F3 and F4 selected for treatment 20% 15,000 started treatment, 33% SOF+PEG-RBV 67% SOF+RBV By the end of 2014, 899 patients received triple therapy were included in this analysis and have currently LED SOF reached PAR/r-OBM12PAR/r-OMB weeks PAR/r-OMB after the ASV+BCV+DCV end 12 wks RBV Naiive RBV Experienced of therapy. 1. He zode C, et al. Gut, 2014 2. Moreno, C., et al. J Hepatol, 2014, 3. Lawitz, E., et al. N Engl J Med, 2013. 4. Ruane P et al. EASL 2014, 5. Esmat G el al. AASLD 2014, 6. Kapoor et al. AASLD 2014, 7. Pol S. et al. Hepatology 2014
Outcome of treatment of 899 patients (F3&F4 compensated) with Triple therapy 4 pts stopped @W4 4 pts stopped @W8 899 triple therapy 2 pts stopped due to severe anemia 5 pts stopped due to hepatic decompensation 1 mortality (esophageal bleeding) 8 DC ETR 96% 27 positive viremia 864 negative viremia SVR 86% 91 positive viremia (relapser) 773 Negative viremia
Relapse rate 11% DC, 8 Positive, 91 NA, 27 SVR 86% Negative, 773
Demographic features of the studied patients SVR (n=773) non SVR (n=126) P value Gender M/F 496/277 84/42.586 Age Mean ±SD 52.8±7.9 51.5±9.1.092 BMI Mean ±SD 28.7±4 29.4±4.116 DM No (%) 97 (13%) 21 (17%) 0.20 Treatment Experienced No (%) 285 (37%) 57 (45%).073
Baseline lab results SVR non SVR P value Mean SD Mean SD ALT 64.48 44.92 75.49 52.72 0.015 AST 72.81 39.50 85.27 48.40 0.008 log_10_baseline_viremia 5.57 0.84 5.65 0.88 0.355 AFP (IU/L) 16.64 40.82 33.16 65.51 0.008 Albumin (g/dl) 4.00 0.49 3.86 0.53 0.005 Total BILIRUBIN (mg/dl) 0.91 0.44 0.98 0.40 0.111 Indirect Bilirubin (mg/dl) 0.59 0.42 0.65 0.32 0.354 TSH 1.68 1.03 1.59 1.02 0.413 WBCx10^3/mm^3 5.86 3.53 5.84 1.68 0.947 ANCx10^3/mm^3 2.98 1.75 2.84 1.04 0.449 Hb (G/L) 13.67 1.56 13.87 1.64 0.192 plateletsx10^3/mm^3 153.78 53.26 155.86 47.90 0.683 PC (%) 85.31 12.40 83.73 12.38 0.206 INR 1.14 0.17 1.19 0.27 0.072 Creatine (mg/dl) 0.85 0.27 0.88 0.53 0.363
95% CI for predictor for failure of treatment in the 899 studied patients 3 2.5 2 1.5 1 0.5 0 Age ALT T exp AFP Albumin Hb LC
SVR in the studied patients SVR 100 95 90 85 80 75 70 65 60 55 50 86 Overall (n=899) 83 84 previous treatment (n=342) cirrhotic (n=479) 80 Varices (n=166) 85 85 Splenomegaly (n=414) Fib-4 >3.25 (n=445)
No of patients Reported Side effects sideeffects, 194 120 108 no side effects, 705 100 80 60 40 20 72 63 14 Presence of side effects is significantly associated with failure of treatment (OR 1.4, P 0.02) 0 week 1 week 2 week 4 week 12
No of patients Reported Side effects 120 100 80 60 40 20 0 108 72 63 14 week 1 week 2 week 4 week 12 W1 W2 W4 W12 Pseudo-Flu syndrome 94 58 47 10 Others 6 5 5 RASH 3 1 1 Amnesia 2 1 2 GI symptoms 1 1 4 Hair Loss 1 3 3 Respiratory Disorders 1 3 4 1
Conclusion This interim report of real-life nationwide treatment campaign using SOF-PEG-RBV in patients with advanced fibrosis showed a high SVR rate. Lower serum albumin level is the only predictor of no SVR. More real- life data for both the triple therapy and dual therapy will be available in the next meeting.
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