This lecture is about Treatment of HCV Genotype 4 presented by Dr. Tamer Elbaz, Assistant professor of Hepatology & Gastroenterology, Cairo University. The lecture was presented in the scientific meeting of Internal and Tropical Medicine departments, Ahmed Maher Teaching Hospital titled (Towards Eradication of HCV in Egypt) in celebration of World Hepatitis Day on July 28, 2016. https://www.facebook.com/AMTH.IM https://www.facebook.com/events/1072758396145209/ http://www.no4c.com

1. Management of HCV genotype 4
“EGYPT and worldwide”
Tamer Elbaz, MD

2. Agenda
1
2
3
4
Introduction
HCV studies in Egypt
Results of HCV studies worldwide
New Guidelines
5 Future

3. INTRODUCTION

5. SUDAN
Upper Egypt
19.4%
(95% CI: 17.2-21.6)
Middle Egypt
26.5%
(95% CI: 23.7-29.4)
Alexandria 5.9%
(95% CI: 4.2-7.7)
Lower Egypt
28.4%
(95% CI: 27.1-
29.2)
Cairo
8.2% (95% CI: 6.7-9.8)
L
I
B
Y
A
Red
Sea
Geographic HCV prevalence
National Survey 1996

6. HCV burden in Egypt
Guerra et al., J Viral Hepatitis, 2011
Breban et al., J Viral Hepatitis, 2012
HCV Ab prevalence:
14.7%
up to 41% in studies !!!
Overall HCV viremia: 9.94%
8 million Chronic HCV.
 Estimated 150 000 new
infections per year.
HCV prevalence in 15-59 years old, DHS Egypt, 2008
(n=11,126)

7. How many people knew they are positive for HCVAb?

8. How many people knew they are positive for HCVAb?
3.8% only !!!

10. EGYPT
For prevalence and more specifically,
• Among Pregnant women: 5-15%
• Among blood donors: 5-25%
• Multi transfused patients: 10-55%
• Among dialysis patients: 50-90%

12. EGYPT
No evidence of statistically significant decline in
HCV prevalence OVER TIME in both general
population and high risk population.

13. EGYPT
No evidence of statistically significant decline in
HCV prevalence OVER TIME in both general
population and high risk population.
THAT WAS BEFORE THE ERA OF DAAs

14. ASSESSMENT OF HEPATIC
FIBROSIS

16. Fibroscan
16

17. Non invasive detection of
hepatic fibrosis
Fib-4 Formula
17
http://gihep.com/calculators/hepatology/fibrosis-4-score/

18. Non invasive diagnosis of
Advanced hepatic fibrosis(>F2)
AUC
No of
patients
Best
cutoff
sensitivity specificity PPV NPV accuracy LR+ LR-
*Fib-4 0.71 36841 1.45 0.69 0.63 0.28 0.90 0.63 1.9 0.49
♠Fibroscan 0.82 231 9.5 0.82 0.87 0.68 0.93 0.86 6.52 0.20
*National Committee for control of viral hepatitis,
NNTC data , Jan 2014
♠ Esmat et al, Arab Journal of Gastroenterology
14 (2013) 109–112

21. HCV STUDIES IN EGYPT

23. Response Rates of treated patients
0
10
20
30
40
50
60
70
80
90
EVR Week 24
respone
ETR SVR
88.5
68
62
54
Percent
Ministry of Health, Egypt
National Committee for Control of Viral Hepatitis
National HCV Treatment Program

26. NS5B - NI
Intermediate potency
Pan genotypic coverage
High barrier to resistance
NS5B - NNI
Intermediate potency
Limited genotypic coverage
Low barrier to resistance
NS3/4A Inhibitors
High potency
Limited genotypic coverage
Low barrier to resistance
NS5A Inhibitors
High potency
Multi genotypic coverage
Intermediate barrier to
resistance
DAA

27. Characteristics of DAA
Schinazi, et al. Liver Int 2014;34 Suppl 1:69-78
DAA
PI 1st
generation
PI 2nd
generation
NS5A Inh. 1st
generation
NS5A Inh. 2nd
generation
NS5B
nucleos(t)ide
inh.
NS5B non
nucleos(t)ide
inh.
Efficacy
Resistance
profile
Pangenotypic
efficacy
Adverse
events
Drug-drug
interaction
Good profile Average profile Least favorable profile

28. This slide represents just a small selection of studies and regimens in current clinical development – other combinations are therefore possible
In different patient
types
• Different genotypes
• Treatment-naive
• Null-responders to
prior therapy
• Intolerant to previous
therapy
Alfa RBV
NS5A
Alfa, peginterferon alfa-2a; lambda, peginterferon lambda-1a; RBV, ribavirin

47. HCV TREATMENT
WORLDWIDE

48. Different Sof. studies

49. SOF + RBV: In genotype 4
Ruane PJ, et al. EASL 2014. P1243
Ruane PJ, et al. AASLD 2013. Abstract 1090 Ruane PJ, et al. EASL 2014. P1243
68
93
79
100
59
87
0
20
40
60
80
100
12 Week
SOF + RBV
24 Week
SOF + RBV
12 Week
SOF + RBV
SVR12(%)
24 Week
SOF + RBV
Treatment
naïve
Treatment
experienced
13/1511/14 10/1714/14
This study done on 60 Egyptians (G4)
living in USA, 20% of them are cirrhotics.
All
12 Week
SOF + RBV
24 Week
SOF + RBV
21/31 27/29

50. PEARL 1 INTERFERON-FREE REGIMENS
OF ABT-450/R + ABT-267 WITH OR WITHOUT
RIBAVIRIN
In 135 Ch HCV GENOTYPE 4 Patients

56. VERY NEAR FUTURE

57. ELBASVIR / GRAZOPREVIR
“ZAPATIER”

58. Elbasvir (NS5A inhibitor)
Grazoprevir (NS3/4A inhibitor)

59. C-WORTHY study
EBR/GZR in managing chronic HCV genotype 1 different
populations including those who are difficult to treat such
as cirrhotic patients and previous null responders to
pegylated interferon therapy.

62. C-SALVAGE study
• Elbasvir and grazoprevir in managing chronic HCV
genotype 1 patients who experienced previous treatment of
pegylated interferon and ribavirin plus either boceprevir,
telaprevir or simeprevir.

63. C-SALT study
Phase II trial studied decompensated patients who were
Child Pugh class B and who were treated using EBR/GZR.
Thirty patients with genotype 1 infection were compared to
10 non cirrhotic patients. Grazoprevir was used in half
dosage (50 mg) for cirrhotic patients. The cirrhotic
decompensated group ended up with 90% SVR12
achievement (compared to 100% in non cirrhotic group)
while two patients relapsed.

64. C-SURFER study
•Management of chronic HCV genotype 1 patients (either
treatment naïve or previous experienced) and additionally
had stage 4-5 chronic renal disease (with or without
hemodialysis). Elbasvir and grazoprevir were used for 12
weeks. Hemodialysis dependent patients represented 76%
of total patients.

65. •Eleven patients discontinued treatment (five due to side
effects, 2 were lost to follow up, 1 died, 1 did renal
transplantation, 1 non compliant and 1 withdrawn by
patient). Among patients who continued treatment, SVR12
was achieved in 99% of patients and just one case relapsed
12 weeks after end of treatment.

66. C-SWIFT study
Phase II trial used elbasvir and grazoprevir with sofosbuvir and
reduced treatment duration to 4, 6 and 8 weeks for chronic HCV
genotype 1 (102 patients) while genotype 3 (41 patients) patients
were treated for 8 weeks or 12 weeks.
In genotype 1 patients, SVR12 was achieved in 33%, 87% and
94% of patients treated for 4, 6 and 8 weeks respectively. In
genotype 3 patients, SVR12 was 93% (8 weeks arm) and 100%
(12 weeks arm) if they were non cirrhotic. For cirrhotic patients,
SVR12 was 91% after 12 weeks of treatment.

67. Relapsed patients (of groups of short duration 4, 6 and 8
weeks) were re-treated again with same drugs for 12 weeks
and with adding ribavirin. All such patients achieved SVR12

68. C-EDGE TN study
• Phase III trial (C-EDGE TN) using GZR/EBR combination
therapy to treat different HCV genotypes (1,4,6) for 12
weeks. Recruited patients were treatment naïve cirrhotic
and non cirrhotic cases.

69. •C-EDGE TE study:
Treatment experienced patients.
12 versus 16 weeks.
97% SVR12 compared to 92%

70. •C-EDGE IBLD study:
Hemophilia, Von Willbrand disease, beta thalassemia,
sickle cell anemia
No patients prematurely stopped treatment due to
worsening of underlying IBLD.
SVR4 ranged between 96% and 100%

71. SOFOSBUVIR/VELPATASVIR
“EPCLUSA”

72. Sofosbuvir (NS5B polymerase inhibitor) and velpatasvir
(NS5A inhibitor).

73. “The U.S. FDA approved Epclusa to treat adult patients
with chronic HCV, both with and without cirrhosis
(advanced liver disease). For patients with moderate to
severe cirrhosis (decompensated cirrhosis), Epclusa is
approved for use in combination with the drug ribavirin.
Epclusa is a fixed-dose combination tablet containing
sofosbuvir and velpatasvir.
The first to treat all six major forms of HCV”.
SVR12: 95-99%.

74. RECENT GUIDELINES

87. Thank you