HCV treatment options in clinical practice Current treatment options for HCV-G4 C. Triantos Gastroenterology Department University Hospital of Patras
Conflicts of interest Speaker and research/travel grants from MSD, Roche, Abbvie, Bristol-Myers Squibb, Bayer and Gilead Sciences.
Treatment of Chronic HCV Genotype 4 Background Initial Treatment Retreatment of Prior Non-responders Future Therapies Real Clinical Practice Data Recommendations Not included data on the management of CHC in patients with decompensated cirrhosis, HBV/HIV co-infections and patients with hemoglobinopathies
Global Distribution and Prevalence of Hepatitis C Virus Genotypes Genotype 4 Globally, approximately 20% of all hepatitis C infections, 34 million people are chronically infected with HCV-4 Dominant HCV genotype in Egypt, North Africa, and sub-saharan Africa. Its prevalence has increased in several European countries, which is considered to be largely a consequence of immigration and intravenous drug use Messina J, Hepatology 2015
Epidemiological changes in chronic hepatitis C infection in Greece Savvas, S, Journal of Viral Hepatitis, 2005 Raptopoulou M, Hippoktatia 2011
Prospective studies evaluating a fixed 48-wk treatment using a standard dose of pegylated interferon and ribavirin in patients with hepatitis C genotype 4 Predictors of response to antiviral treatment in patients with hepatitis C virus genotype 4 infection Papastergiou V, World J Clin Cases 2015
Genotype 4 HCV infection is difficult to cure with pegylated interferon and ribavirin. Results from a Greek Nationwide Cohort Study Anagnostou O, Hippokratia 2014
Genotype 4 HCV: Initial Treatment Ledipasvir-Sofosbuvir - NIAID Synergy Ombitasvir-Paritaprevir-Ritonavir - PEARL-I Sofosbuvir + Ribavirin - Egyptian Ancestry Sofosbuvir + Ribavirin + Peginterferon - NEUTRINO
Genotype 4 HCV: Initial Treatment IFN-based Regimens
Sofosbuvir + PEG + RBV: Treatment-Naive HCV GT 1,4,5,6 NEUTRINO Trial Drug Dosing Sofosbuvir: 400 mg once daily Peginterferon alfa-2a: 180 µg once weekly Ribavirin (weight-based and in 2 divided doses): 1000 mg/day if < 75 kg or 1200 mg/day if 75 kg Lawitz E, N Engl J Med. 2013
Sofosbuvir + PEG + RBV: Treatment-Naive HCV GT 1,4,5,6 NEUTRINO Trial: Results Lawitz E, N Engl J Med. 2013
Patients (%) with SVR12 Simeprevir + Peginterferon + Ribavirin in Genotype 4 RESTORE trial, Moreno C, J Hepatology 2015 Open-label, phase 3, n = 107, 8 centres in France and Belgium TN (n = 35) or TE relapsers (n = 22) Experienced (Nonresponder): partial (n = 10), null (n = 40) METAVIR Fibrosis Stage: F4 = 29%; F3 = 14% lack of a control arm serious AEs were infrequent (4.7%) 100 80 60 65 83 86 60 40 40 20 0 All Treatment-Naïve Relapsers Partial Null
High efficacy of a 12-week simeprevir plus peginterferon alfa 2a/ribavirin regimen in treatment-naïve patients with chronic HCV genotype 4 infection and mild-to-moderate fibrosis Phase-3, open-label study Europe and Saudi Arabia G4 patients who achieved HCV-RNA <25 IU/mL (detectable/undetectable in IL28B CC, undetectable in CT/TT) at Week 2, and undetectable at Weeks 4 and 8 (Roche COBAS Taqman ), stopped all treatments at Week 12 (12-week group). Otherwise, PR was continued to Week 24 (24-week group). The 24-week group also included patients discontinuing treatment early for any reason. 67, G4 patients were enrolled (male: 69%, white: 80%, G4a/d/other: 40/37/23%, METAVIR F0 1/F2: 81/18%) SVR12 rates were 97% (33/34) and 84% (21/25) for the 12-week and 24-week groups, respectively Asselah T, AASLD 2015
Daclatasvir + Peg/RBV in Treatment-Naïve Genotype 4, COMMAND-4 Study, Phase 3 randomized, placebo-controlled trial, United States and Europe HezodeC, ID Week. 2014
Genotype 4 HCV: Initial Treatment All-oral Regimens
Ledipasvir-Sofosbuvir in Genotype 4 F4, 33% single-site trial nonrandomised enrolment without ribavirin Kohli A, Lancet Infect Dis. 2015
LDV/SOF in GT 4 Patients Multicenter study in TN/TE GT 4 or 5 patients in France Open-label, single-arm study: 12 wks LDV/SOF 90/400 mg QD LDV/SOF for 12 weeks was highly effective and well tolerated, without the need for RBV Naïve n=22 Experienced n=22 100 SVR12 96 91 91 100 Mean age, years (range) 52 (21 69) 50 (30 62) Male, n (%) 11 (50) 17 (77) White, n (%) 19 (86) 17 (77) Cirrhosis, n (%) 1 (5) 9 (41) IL28B non-cc, n (%) 15 (68) 21 (95) Mean HCV RNA, log 10 IU/mL (range) 6.0 (5.1 6.8) 6.3 (5.6 7.5) GT 4a, n (%) 13 (59) 12 (55) GT 4d, n (%) 5 (23) 5 (23) GT 4b, 4f, 4m, 4o, 4r, n (%) 4 (18) 5 (23) 80 60 40 20 0 21/22 20/22 31/34 10/10 TN TE No Yes Treatment Status Cirrhosis Abergel EASL, 2015
Ombitasvir + Paritaprevir + Ritonavir +/- RBV in HCV GT4 PEARL-I: Baseline demographics and disease characteristics France, Hungary, Italy, Poland, Romania, Spain,Turkey, and USA large study lack of examination of a ribavirin-free regimen in treatment experienced patients. only non-cirrhotic patients Drug Dosing Ombitasvir (25 mg once daily), Paritaprevir (150 mg once daily), Ritonavir (100 mg once daily) Ribavirin (RBV): weight-based and divided bid (1000 mg/day if < 75kg or 1200 mg/day if 75kg) Hézode C, Lancet. 2015
Ombitasvir + Paritaprevir + Ritonavir +/- RBV in HCV GT4 PEARL-I: Results Hézode C, Lancet. 2015
Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir Co-Administered with Ribavirin in Adults with Genotype 4 Chronic Hepatitis C Infection and Cirrhosis (AGATE-I) Canada, Europe and US Asselah T, AASLD 2015
Efficacy and Safety of Co-Formulated Ombitasvir/Paritaprevir/ Ritonavir with Ribavirin in Adults with Chronic HCV Genotype 4 Infection in Egypt (AGATE-II) Esmat G, ASLD 2015
Sofosbuvir and Ribavirin in HCV Genotype 4 Egyptian Ancestry Trial Drug Dosing Sofosbuvir: 400 mg once dailyweight-based Ribavirin (in 2 divided doses): 1000 mg/day if < 75 kg or 1200 mg/day if 75 kg Ruane PJ, J Hepatol. 2015
Sofosbuvir and Ribavirin in HCV Genotype 4 Egyptian Ancestry Trial: Results absence of complete prior treatment histories in all patients small number of patients infected with non-4a HCV. Ruane PJ, J Hepatol. 2015
Sofosbuvir plus Ribavirin in the Treatment of Egyptian Patients with Chronic Genotype 4 HCV Infection An integrated analysis was conducted of data from treatment-naïve and treatmentexperienced patients enrolled in Study GS-US-334-0114 in the USA (n=60) and GS-US-334-0138 in Egypt (n=103). Doss W, AASLD 2015
Retreatment of GT4 Chronic HCV Ledipasvir-Sofosbuvir - NIAID Synergy (Genotype 4) Ombitasvir-Paritaprevir-Ritonavir - PEARL-I Sofosbuvir + Ribavirin - Egyptian Ancestry
Patients (%) with SVR12 Retreatment of GT4 Chronic HCV - IFN-based Regimens Simeprevir + Peginterferon + Ribavirin in Genotype 4 (RESTORE) 100 80 60 65 83 86 60 40 40 20 0 All Treatment-Naïve Relapsers Partial Null Moreno C, J Hepatology 2015
Retreatment of GT4 Chronic HCV All-oral Regimens Kohli A, Lancet Infect Dis. 2015 Abergel, EASL, 2015 Hézode C, Lancet. 2015 Ruane PJ, J Hepatol. 2015
Treatment of Hepatitis C Genotype 4 patients with Simeprevir and Sofosbuvir: Preliminary Results from a Phase IIa, Partially Randomised, Open-label Trial conducted in Egypt (OSIRIS) SVR 12, 100 % independently of prior PR response or cirrhosis G. Van Dooren, AASLD 2015
Figure 1. Study Designs Advanced cirrhosis ALLY-1 c Post-liver transplant Treatment-naive ALLY-2 Treatment-experienced Sofosbuvir + Daclatasvir +RBV DCV 60 mg + SOF 400 mg + RBV DCV 60 mg + SOF 400 mg + RBV DCV 30/60/90 mg + SOF 400 mg SVR12 b Regimen Study SVR 12 DCV 30/60/90 mg + SOF 400 mg DCV 30/60/90 mg + SOF 400 mg DCV + SOF + RBV ALLY-1 100 (4) (advanced cirrhosis) Treatment-naive ALLY-3 Treatment-experienced AI444040 d GT 1 Treatment-naive GT 2/3 Treatment-naive DCV 60 mg +SOF 400 mg DCV 60 mg +SOF 400 mg A: SOF 7 d, then DCV 60 mg + SOF 400 mg C: DCV 60mg + SOF 400 mg E: DCV 60 mg + SOF 400 mg + RBV G: DCV 60 mg + SOF 400 mg H: DCV 60 mg + SOF 400 mg + RBV B: SOF 7 d, then DCV 60 mg + SOF 400 mg D: DCV 60 mg + SOF 400 mg F: DCV 60 mg + SOF 400 mg + RBV SVR12 b GT 1 PI failures I: DCV 60 mg + SOF 400 mg J: DCV 60 mg + SOF 400 mg + RBV Week 0 Week 8 Week 12 Week 24 Week 36
HCV genotype 4: SVR with different direct-acting antivirals (DAAs) (with or without IFN). Asselah T, Journal of Hepatology 2015
Future Regimens for GT-4
Future Regimens for GT-4 Daclatasvir and Asunaprevir Plus Peginterferon Alfa-2a and Ribavirin Daclatasvir, asunaprevir, and beclabuvir Sofosbuvir-Velpatasvir Grazoprevir-Elbasvir Ravidasvir (PPI-668) and Sofosbuvir
Daclatasvir and Asunaprevir Plus Peginterferon Alfa-2a and Ribavirin in Patients With HCV Genotype 1 or 4 Infection: Phase 3 HALLMARK-QUAD, Jensen IDWeek 2014
A randomized trial of daclatasvir in combination with asunaprevir and beclabuvir in patients with chronic hepatitis C virus genotype 4 infection RCT, 1:1 to receive a twice-daily oral regimen comprising of 75 mg or 150 mg of beclabuvir, each with daclatasvir (30 mg) and asunaprevir (200 mg), for 12 weeks with 48 weeks of post-treatment follow up. Patients with compensated cirrhosis were permitted although none were enrolled. Hassanein T, Journal of Hepatology 2015
ASTRAL-1, -2, -3, -4 Trials Sofosbuvir/ Velpatasvir FDC ± RBV in GT1-6 HCV Multicenter, randomized phase III trials in Tx-naive and Tx-experienced pts 12 wks 24 wks ASTRAL-1 [1] : GT 1, 2, 4, 5, or 6 HCV (N = 740) ASTRAL-2 [2] : GT2 HCV (N = 266) Sofosbuvir/Velpatasvir (n = 624) Placebo QD (n = 116) Sofosbuvir/Velpatasvir (n = 134) Sofosbuvir + RBV (n = 132) Gen 4, SVR 12 100% (116/116) ASTRAL-3 [3] : GT3 HCV (N = 552) ASTRAL-4 [4] : GT1-6 HCV and CTP B cirrhosis (N = 267) Sofosbuvir/Velpatasvir (n = 277) Sofosbuvir + RBV (n = 275) Sofosbuvir/Velpatasvir (n = 90) Sofosbuvir/Velpatasvir + RBV (n = 87) Sofosbuvir/Velpatasvir (n = 90) Sofosbuvir/velpatasvir 400/100 mg QD 1. Feld JJ, et al. NEJM 2015. 2. Sulkowski MS, et al. AASLD 2015. Abstract 205. 3. Mangia A, et al. AASLD 2015. Abstract 249. 4. Charlton MR, et al. AASLD 2015. Abstract LB-13.
Grazoprevir/Elbasvir Studies: Overview C-EDGE TN C-EDGE TE C-EDGE Coinfection C-SALVAGE C-SCAPE C-WORTHY C C-SWIFT C-SURFER 12 wks of grazoprevir/elbasvir in treatment-naive pts with GT1, 4, or 6 HCV infection 12 or 16 wks of grazoprevir/elbasvir ± RBV in pts with GT1, 4, or 6 HCV and previous failure of pegifn/rbv 12 wks of grazoprevir/elbasvir in HCV treatment-naive pts coinfected with HIV and GT1, 4, or 6 HCV 12 wks of grazoprevir/elbasvir + RBV in pts with GT1 HCV and previous failure of HCV PI + pegifn/rbv 12 wks of grazoprevir ± elbasvir ± RBV in treatment-naive, noncirrhotic pts with GT2, 4, 5, or 6 HCV 8 wks of grazoprevir/elbasvir ± RBV in treatment-naive, noncirrhotic pts with GT1b HCV Short-duration therapy with grazoprevir/elbasvir + sofosbuvir in treatment-naive, GT1 or 3 HCV infected pts ± cirrhosis 12 wks of grazoprevir/elbasvir in pts with GT1 HCV infection and stage 4 or 5 CKD
Grazoprevir/Elbasvir Studies: Overview C-EDGE TN C-EDGE TE C-SCAPE 12 wks of grazoprevir/elbasvir in treatment-naive pts with GT1, 4, or 6 HCV infection 22% cirrhotics, SVR12, 100% (18/18) 12 or 16 wks of grazoprevir/elbasvir ± RBV in pts with GT1, 4, or 6 HCV and previous failure of pegifn/rbv 34 % cirrhotics SVR 4, GZR/EBR - 78 % (7/9) - GZR/EBR+RBV 100 % (15/15) 12 wks of grazoprevir ± elbasvir ± RBV in treatment-naive, noncirrhotic pts with GT2, 4, 5, or 6 HCV N=20, SVR12 GZR/EBR 100 % - GZR/EBR+RBV 90 % C-EDGE CO-STAR (PWID) (+- cirrhosis), SVR12 92 % (11/12)
Grazoprevir/Elbasvir Studies: Overview C-EDGE TN C-EDGE TE C-SCAPE 12 wks of grazoprevir/elbasvir in treatment-naive pts with GT1, 4, or 6 HCV infection 22% cirrhotics, SVR12, 100% (18/18) 12 or 16 wks of grazoprevir/elbasvir ± RBV in pts with GT1, 4, or 6 HCV and previous failure of pegifn/rbv 34 % cirrhotics SVR 4, GZR/EBR - 78 % (7/9) - GZR/EBR+RBV 100 % (15/15) 12 wks of grazoprevir ± elbasvir ± RBV in treatment-naive, noncirrhotic pts with GT2, 4, 5, or 6 HCV N=20, SVR12 GZR/EBR 100 % - GZR/EBR+RBV 90 % C-EDGE CO-STAR (PWID) (+- cirrhosis), SVR12 92 % (11/12)
GT4 infected patients enrolled in the GZR/EBR phase 2/3 clinical program Asselah T, AASLD 2015 Child-Pugh A cirrhosis. SVR 12 (TE) - 76, 4% (13/17) (includes 13 pts treated for 12 wks and 4 pts treated for 16/18 wks). Jacobson IM, et al. AASLD 2015
High Virologic Response Rate in Egyptian HCV-Genotype 4 Patients Treated with Ravidasvir (PPI-668) and Sofosbuvir: Results of a Large Multicenter Phase 3 Registrational Trial Esmat G, AASLD 2015
Genotype 4 - Real Clinical Practice Data - 1 SOF/PEG/RBV IFN/RBV/SOF N=24 M.H.Wehmeyer GERMA NY Dig Liver Dis 2015 Cirrhosis, 23.1% TE, 50 % SVR12 86.4% SOF/PEG/RBV SOF/PEG/RBV N=16 N=4 S. Alqahtani Cirrhosis, USA 23 77 % EASL 2015 TE, Cirrhosis 50-100 38% % SVR12, TE, 70 67 % -88 % SVR 4, 88% SOF/PEG/RBV N=11 K. Bichoupan USA EASL 2015 54% had a FIB-4 score 3.25 NA SVR12, 82% SOF/PEG/RBV D.Ouzan FRANCE EASL 2015 Cirrhosis 77% TE 100 % SVR 12, 67 % SOF/RBV SOF/RBV N=2 K. Bichoupan USA EASL 2015 54% had a FIB-4 NA SOF/RBV N=2 Cirrhosis, 34 54 % TE, 59 score % 3.25 SVR12, 50-96 % SVR12, 50% SOF/RBV M=45 Moutaz F. Derbala QATAR AASLD 2015 Cirrhosis, 34.3% TE 58.8% SVR4, 96%
Genotype 4 - Real Clinical Practice Data - 2 SOF/DCV SOF/DCV N=33 ANRS CO22 HEPATHER FRANCE EASL 2015 Cirrhosis 78,8 % TE 70,7 % SVR 12, 12 W 90 % SOF/DCV N=1 Cirrhosis, 78 % TE, 71 % SVR 12, 24 W 100 % SOF/DCV/RBV N=15 12 W 90 % ANRS CO22 FRANCE EASL Cirrhosis 86,7 % 24 TE W 66-% 100 % SVR 12, HEPATHER 2015 12 W 100 % SOF/DCV/RBV N= 2 Cirrhosis, 77-87 % TE, 66-100 % SVR 12, 24 W 100 % 12 W 100 % SOF/DCV/RBV D.OUZAN FRANCE EASL 2015 24 W 100 % Cirrhosis 77% TE 100 % SVR 12, 100 % SMV/DCV SMV/DCV N=47 SMV/DCV Mohamed Alzaabi N=2 UNITED ARAB Cirrhosis, AASLD 69-732015 % Cirrhosis, 72.3 TE, 56 % TE, 56.1% SVR12, 85 % SVR 4, 85% EMIRATES SMV/DCV N=47 E. Taleb UNITED ARAB EMIRATES AASLD 2015 Cirrhosis, 68,4 % TE 56.1% SVR12, 85 %
Genotype 4 - Real Clinical Practice Data - 3 SOF/SMV+/- RBV SOF/SMV+/- ribavirin SOF/SMV+/- RBV (G 1/4) SOF/SMV+/- RBV (G 1/4) N=73 C. Moreno BELGIUM AASLD 2015 Cirrhosis 56.2 % Te 78.8 % W12, 74 % N=108 Z. Kayali USA AASLD 2015 Cirrhosis 100 % TE 46% SVR12, 77% N=130 E. Nguyen-Khac FRANCE AASLD 2015 Cirrhosis 66.9%. TE 70 % SVR4 88.23% SMV/SOF N=19 E. Taleb UAE AASLD 2015 Cirrhosis 68.4 TE 56.1% SVR12, 94% SOF/SIM N=6 Cirrhosis, 34-100 % TE, 50-73 % SVR 12, 81-100 % SOF/SMV N=40 F. Derbala Qatar AASLD 2015 Cirrhosis 34.3% TE 58.8% SVR4 96% SOF/SIM/RBV N= 7 Cirrhosis, 77-87 % TE, 52-100 % SVR 12, 74-100 % SOF/SIM N=6 S. Alqahtani USA EASL 2015 Cirrhosis 38% TE 50 % 100% SOF/SIM + RBV N=6 S. Alqahtani USA EASL 2015 Cirrhosis 33% TE 83 % 100% SOF/SIM N=32 A.M. Hefner USA EASL 2015 Cirrhosis 100 % TE 71% SVR 12, naive 80%, TE 81% SOF/SMV N=27 K. Bichoupan USA EASL 2015 54% had a FIB-4 score 3.25, NA SVR12 81% SOF/SMV/RBV N=70 K. Bichoupan USA EASL 2015 54% had a FIB-4 score 3.25, NA SVR12 86% SOF/SIM N=22, 12 w N=32 24 w ANRS CO22 HEPATHER FRANCE AASLD 2015 Cirrhosis 53 %, 12 w Cirrhosis 61 %, 24 w TE 73 % SVR 12, 12 W 84 % 24 W 100 % SOF/SIM/RBV N=24, 12 w N=32 24 w ANRS CO22 HEPATHER FRANCE AASLD 2015 Cirrhosis 67 %, 12 w Cirrhosis 89 %, 24 w TE 71 % SVR 12, 12 W 100 % 24 W 100 % SOF/SIM/RBV D.OUZAN FRANCE EASL 2015 Cirrhosis 77% TE 100 % SVR 12, 100 %
Real Clinical Practice Data in Greece, n=52 SVR12, % Pts 1/ 4 /0 4/ 20/ 4 4/ 0/ 0 6/ 0/ 3 1/ 5/ 0 Papatheodoridis G, ΠΓΣ 2015
Recommendations on Treatment of Hepatitis C Genotype 4 AASLD Treatment naïve ledipasvir (90 mg)/sofosbuvir (400 mg) for 12 weeks paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) and weight-based RBV for 12 weeks sofosbuvir (400 mg) and weight-based RBV for 24 weeks Alternative regimen for patients eligible to receive interferon sofosbuvir (400 mg) and weight-based RBV plus weekly PEG-IFN for 12 week Prior treatment with PEG-IFN and RBV has failed ledipasvir (90 mg)/sofosbuvir (400 mg) for 12 weeks paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) (PrO) and weight based RBV for 12 weeks sofosbuvir (400 mg) for 12 weeks and daily weight based RBV plus weekly PEG-IFN for 12 weeks sofosbuvir (400 mg) and weight-based RBV for 24 weeks.
Recommendations on Treatment of Hepatitis C Genotype 4 European Association for the Study of the Liver cirrhosis ΚΕ.ΕΛ.Π.ΝΟ 12 w SMV+PR / PR x12/12 ή 36 w 24 w SOF/LDV SOF/LDV + RBV x 12 w + PR x 24 ή 48 w x 12 w x 12 w Sof +DCV SOF+DCV +RBV x12 ή 24 w
Recommendations on Treatment of Hepatitis C Genotype 4 European Association for the Study of the Liver 96 % 83 % 96 % 100 % cirrhosis 100 % RWD 100 % RWD 70-90 % 100 % 97 % 100 % RWD 100 % ΚΕ.ΕΛ.Π.ΝΟ 12 w SMV+PR / PR x12/12 ή 36 w 24 w SOF/LDV SOF/LDV + RBV x 12 w + PR x 24 ή 48 w x 12 w x 12 w Sof +DCV SOF+DCV +RBV x12 ή 24 w
Treatment recommendations for retreatment of HCV-monoinfected or HCV/HIV coinfected patients with chronic hepatitis C who failed to achieve an SVR on prior antiviral therapy containing one or several DAA(s) EASL - Genotype 4 Patients that failed SOF alone, in combination with RBV or in combination with PegIFN-α and RBV GT4 LDV/SOF + RBV 12 wk or 24 wk (if F3) OBV/PTV/R TV + RBV 12 wk or 24 wk (if F3) SOF + SMV + RBV 12 wk or 24 wk (if F3) SOF + DCV + RBV 12 wk or 24 wk (if F3) Patients that failed PegIFN-α, RBV and SMV or SOF and SMV GT1 or 4 LDV/SOF + RBV 12 wk SOF + DCV + RBV 12 wk or 24 wk (if F3) Patients that failed PegIFN-α, RBV and DCV GT4 SOF + SMV + RBV 12 wk or 24 wk (if F3) Patients that failed SOF and DCV or LDV/SOF GT4 SOF + SMV + RBV 12 wk or 24 wk (if F3) Patients that failed OBV/PTV/RTV and DSV (GT1) or OBV/PTV/RTV (GT4) GT4 LDV/SOF + RBV 12 wk or 24 wk (if F3) SOF + SMV + RBV 12 wk or 24 wk (if F3) SOF + DCV + RBV 12 wk or 24 wk (if F3)
Summary Genotype 4 hepatitis C virus infection is not common in the United States, but it is highly prevalent in the Middle East, Africa, and Southern Europe. HCV-G4 has been considered difficult to treat with pegylated interferon (PegIFN) and ribavirin (RBV) treatment, with sustained virological response (SVR) rates around 50% The main limitations on HCV-G4 are their small sample size and the relatively mild stage of liver diseases included in patients There are effective regimens There is optimism for patients with genotype 4 HCV infection, with several promising ongoing trials. With these excellent data, the next steps will be to improve screening and access to therapy