global prevalence of hepatitis c - egyptian french...
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Global Prevalence of Hepatitis CGlobal Prevalence of Hepatitis C
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� Egypt has one of the world’s highest prevalence of Hepatitis C
� Unfortunately, till 2007 we did not have a national control program for � Unfortunately, till 2007 we did not have a national control program for
control of viral hepatitis
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�� In Egypt,In Egypt, a high homology of HCV subtypes, 96% of
which is genotype genotype 44a,a, strongly suggests a local epidemiclocal epidemic
of HCV throughout the general population.
� This genotype would have existed almost 100 years ago
and the current high prevalence is the result of a rapid rapid
spreadspread during four decades since 1940s.
Tanaka et al, Tanaka et al, 20042004
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� The risk factor for HCV transmission that specifically
sets Egypt apart from other countries is a personal
history of parenteralparenteral antischistosomalantischistosomal therapy (PAT). therapy (PAT).
� This intensive transmission established a largelarge
reservoirreservoir of chronic HCV infection, responsible for the
high prevalencehigh prevalence of HCV infection and current high
rates of transmission.
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� A review of the Egyptian parenteralparenteral
antischistosomalantischistosomal therapytherapy (PAT) mass-treatment
campaigns, discontinued only in the 1980s,
show a very high potential for transmission of
blood-borne pathogens.
(FRANK ET AL., 2000; LANCET)
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� unscreened blood transfusions/products
� unsafe injections
� exposed health care workers
� hemodialysis
� failure to sterilize medical equipment� failure to sterilize medical equipment
� dental and “traditional” medicine
� injection drug users� rare :high risk sexual practices, horizontal and
perinatal transmission
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The national committee for control of viral hepatitis was established by the Ministry of Health (MOH)in 2007
Objectives:� National Survey & Burden of Disease
� Treatment Program� Treatment Program
� Prevention
� Awareness and media Campaign
� Infection control
� Clinical Research
� Management of advanced liver disease
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The main goals of the National Control StrategyThe main goals of the National Control Strategy
� Detect the prevalence and incidence of HBV and HCV
� Reduce the prevalence of chronic HBV and HCV infection by 20% of 2008 levels
by 2012
� Expand access to treatment to within 100 km for all Egyptians and treat 50% of
persons needing treatment by 2014.
� Continue to produce high-quality scientific research
� Ensure program sustainability
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�� National Survey & Burden of DiseaseNational Survey & Burden of Disease
� Treatment Program
� Prevention
� Awareness and media Campaign� Awareness and media Campaign
� Infection control
� Clinical Research
� Management of advanced liver disease
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� Under auspices of Ministry of Health.
� Implemented by El-Zanaty in association with Demographic
and Health survey (DHS) Egypt and MACRO international
Funding from USAID and UNICEF.� Funding from USAID and UNICEF.
� Hepatitis C testing undertaken at the central Laboratory of
MOH with external quality assurance at the Theodor Bilharz
Research Institute.
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� Hepatitis C knowledge
� Self reported prevalence of HCV
� Hepatitis C testing
� Protocol � Protocol
� Coverage
� Return of results
� Prevalence of HCV
� Disease Burden
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� Household survey in 28 governorates.
� Total of 12,780 women and men aged 15 – 59 consented to
blood sampling.
� Venous blood samples, frozen in liquid nitrogen containers,
and transported twice weekly to Central Laboratory in Cairo
for testing.
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Women % Men %
Know about HCV 79 85
Source of knowledgeTelevisionFriends / Relatives
93 23
8829
TelevisionFriends / Relatives
93 23
8829
Know about transmission 70 78
Ever tested for HCV 2 5
Ever treated for HCV 0.4 1
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� ELISA test used to determine presence of antibodies .
� Real time PCR used for testing for HCV RNA for all antibody positive samples to detect infections in active phase.active phase.
� External quality control conducted for 2 % of ELISA negatives, 5% of PCR positives and all PCR negatives.
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� HCV Antibodies detected in 14% of all individuals tested and evidence of active infection (positive PCR) detected in 9.8%.
� Infection rates rise sharply with age; persons 50 years and older 7-8 times more likely to be infected than and older 7-8 times more likely to be infected than individuals under age 30.
� Prevalence in males higher than females.
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� Rural rate 80% higher than urban rate.
� Lower Egypt the highest level and Frontier Governorates the lowest.Governorates the lowest.
� Individuals reporting schistosomiasis treatment had very high infection rate.
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10
12
14
16
1815
12
17
11
0
2
4
6
8
Total Women Men
9
7
11
HCV antibody HCV RNA
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23
29
3940
2325
25
30
35
40
45
4 5 6
12
14
23
3 3 3
7
8
13
17
0
5
10
15
20
25
15 -19 20 -24 25 -29 30 -34 35 -39 40 -44 45 -49 50 -54 55 -59
HCV antibody HCV RNA
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15
20
25
3029
13
18
29
0
5
10
15
Received Didn't receive/DK Don't know
13
8 9
HCV antibody HCV RNA
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Alexandria 5.9%
Lower Egypt
28.4%
Cairo
8.9%
L
I
B
Y
Geographic HCV prevalence
SUDAN
EGYPT
Upper Egypt
19.4%
Middle Egypt
26.5%
Y
A Red
Sea
Frank et al., (2000)
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815.2
5.5
9.6
0
10
20 %HCV RNA
POSITIVE
%HCV AB POSITIVE
WOMEN
12.721.1
9
14.4
0
10
20
30
URBAN RURAL
% HCV RNA POSITIVE
%HCV AB POSITIVE
MEN
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21.7
16.1
7.1 6.7
14.5
10.1
4.3 4.1
0
5
10
15
20
25
%HCV AB POSITIVE
%HCV RNA POSITIVE
WOMEN
0
30
24.3
15.3 13.9
21.6
15.210.6 9.7
0
5
10
15
20
25
30
35
NO EDUCATION SOME PRIMARY PRIMARY COMPLETE/SOME SECONDARY
SECONDARY COMPLETE /HIGHER
MEN
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13.6
22.2
13.2
25.3
12.215.3
9.2
14.1
8.6
16.7
7.9 7.3
5
10
15
20
25
30
%HCV AB POSITIVE
%HCV RNA POSITIVE
WOMEN
0
22.126.7
20.1
31.5
17.9
31.8
15.518.2
14
21.1
12.4
26.7
05
101520253035
SURGERY BLOOD Tx DENTAL ANTI SCHISTO INJECTION INJECTION FOR OTHERS REUSED SYRINGES
MEN
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15.8 15.713.8
9.5
6.6
10.1 10.58.6
6.14.3
0
5
10
15
20
%HCV AB POSITIVE
%HCV RNA POSITIVE
WOMEN
0
21.118.7 19
13.9 14.215.112.4 13.2
10.2 9.9
0
5
10
15
20
25
LOWEST SECOND MIDDLE FOURTH HIGHEST
MEN
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� Multivariate regression was used to estimate independent effects of risk factors on seropositivity of HCV
� Among those over 20 years of age, the following risk factors were significantly associated with seropositivity:� Age
� Male gender
Anti-schistosomiasis treatment � Anti-schistosomiasis treatment
� Blood transfusion
� Invasive medical procedure (surgery, catheterization, endoscopy, and/or dialysis)
� Receipt of injections from "informal" health care provider
� Cesarean section or abortion
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Those infected with HCV 100%
No or only mild flu-like symptoms 70-80%
Acute Hepatitis 20-30%
6-7 weeks incubation
years
In HBV: 80% of those infected do not progress to chronic
hepatitis
⇒ > 50% develop chronic active liver disease⇒ 10-15% develop cirrhosis and hepatocellular
carcinoma
Clearance 15-25%
Active liver disease (elev. ALT) 48-56%
Progression to chronic infection 75-85% (Our Data 50-60%)
Normal ALT 24-32%2
0 to 30 years
HCC1-4%
Cirrhosis 8-16%
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� National Survey & Burden of Disease
�� Treatment ProgramTreatment Program
� Prevention
� Awareness and media Campaign� Awareness and media Campaign
� Infection control
� Clinical Research
� Management of advanced liver disease
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� Scaled-up case detection efforts via voluntary counseling and testing.
� Improved access to treatment, including the opening of Viral Hepatitis Treatment Centers (VHTC) : 22 centers Nation-wide
� Reductions in the price of drugs, and expanded subsidization of antiviral � Reductions in the price of drugs, and expanded subsidization of antiviral therapy.
� Attaining optimal clinical management of all patients, (including pediatric patients and persons suffering from advanced liver disease)
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HCV treatment centers
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� Age is from 18 to 60 years.
� The patients must be HCV RNA (PCR) positive.
� BMI ≤ 35BMI ≤ 35
� Liver biopsy in every patient except :
Medical and paramedical Personnel
Genotype 2 & 3
Extrahepatic manifestations of HCV
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� F0 : Treated if ALT is elevated or ≥ A2.
� F1 : treated if ALT is elevated or ≥ A2.
F2 : treated.
Liver biopsy (Metavir score)
� F2 : treated.
� F3 : treated.
� F4 : only those with Child-Pugh class A and NO VARICES
are treated.
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Discontinuation of Treatment
Patients will receive antiviral therapy for 48 weeks unless:
� At 12 weeks : treatment is discontinued for patients who do not show a 2 log decrease in HCV RNA.who do not show a 2 log decrease in HCV RNA.
� At 24 weeks : treatment is discontinued for any patient with detectable HCV RNA by real time PCR.
� At 36 weeks: treatment is discontinued for any patient with a breakthrough.
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Dose of Interferon :
� Peg-IFN alpha-2a
180ug sc once weekly
Peg-IFN alpha-2b
Dose of Antiviral Therapy:
� Peg-IFN alpha-2b
1.5ug/kg sc once weekly
Dose of Ribavirin :
� <75kg : 1000mg/day
� ≥75kg : 1200mg/day
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� Patients with pEVR achieved a low SVR (<30%) with 48 weeks
of therapy, so the decision was not to continue therapy to these
patients.
Patients with a BMI over 30 showed a low SVR (30%) and were � Patients with a BMI over 30 showed a low SVR (30%) and were
treated after they lost weight.
� Patients with a METAVIR F4 showed a low SVR (20%) and were
not treated on the modified national guidelines.
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� F0 : Treated if ALT is elevated or ≥ A2.
� F1 : treated if ALT is elevated or ≥ A2.
� F2 : treated.
� F0 : Not treated.
� F1 : treated if ALT is elevated or ≥ A2.
� F2 : treated.
BEFORE Modification AFTER Modification (2010)
� F2 : treated.� F3 : treated.� F4 : only those with Child-
Pugh class A and NO VARICES are treated.
�� BMI BMI ≤ ≤ 3535..�� Treatment continued for Treatment continued for
patients with patients with pEVRpEVR..
� F2 : treated.� F3 : treated.� F4 : not treated.
�� BMI BMI ≤ ≤ 30 30 . . �� Treatment discontinued for Treatment discontinued for
patients with patients with pEVRpEVR..
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� A Network for all patients’ data from the Viral Hepatitis Treatment Centers nation-wide, was established with the main server located in National Hepatology Institute in Cairo.
� When fully functioning, the NNTC will have full data for pre-enrollment and treatment of 150,000 HCV patients
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(NNTC)
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1 Hardware
2 Software
3 Connection
4 Training
5 Implementation
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Hardware
HQAll
centersHQ
Microsoft Dynamic CRM
High availability
All centers
40 PCs HP
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Software
designed Applied Implemented
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Connection
1st phase
2القاھرة
2ا�سكندرية
الزقازيق
2nd phase
ا�سماعيلية
المنوفية
كفر الشيخ
What have been done
الزقازيق
طنطا
المنصورة
دمياط
كفر الشيخ
قنا
المنيا
أسيوط
بني سويف
سوھاج
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Training
Physician training
lectures
Data Entry personnel
workshops
Hands-on training
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PhysicianData room
Forms revised (date,
physician name, Pt ID)
HQ
Data written
Signed
Given to
nurse
Nurse collects all forms
Forms to data entry employee
Data entry on
computer
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National HCV Treatment ProgramNational HCV Treatment Program
Government expenses,
Private health insurance, 3%
Cash, 8%
METHOD OF PAYMENT
expenses, 38%
Institute of health
insurance, 51%
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National HCV Treatment ProgramNational HCV Treatment Program
Method of Payment: centersMethod of Payment: centers
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341
138
342
0
73
226
356
5
60%
80%
100%
pending
National HCV Treatment ProgramNational HCV Treatment Program
Type of IFNType of IFN
310 272 291
95
0%
20%
40%
TMRI Fatemic
hospital
Kabary Alex Tanta
pending
IFN B
IFN A
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National HCV Treatment Program: OutcomeNational HCV Treatment Program: Outcome
60%
80%73%
PERCENT
EARLY VIROLOGICAL RESPONSE (12 WKS)
0%
20%
40%
NEG 2LOGs POS
6%
21%
PERCENT
PCR RESULT
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31
2153
116 70
70%
80%
90%
100%
83% 90% 99% 96%
National HCV Treatment National HCV Treatment Program Program
Early Early virologicalvirological Response (Response (12 12 weeks): centersweeks): centers
156134
277 181
0%
10%
20%
30%
40%
50%
60%
TMRI Fatemic
hospital
Kabary Alex Tanta
pending
PCR +ve
PCR -ve
N.B: EVR is Per protocol, missing patients excluded
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60.00%
80.00%69.90%
30.10%PERCENT
VIROLOGICAL RESPONSE (24 WKS)
National HCV Treatment Program: OutcomeNational HCV Treatment Program: Outcome
0.00%
20.00%
40.00%
NEG POS
30.10%PERCENT
PCR RESULT
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100.00%69.90%
END OF TREATMENT RESPONSE (48 WKS)
National HCV Treatment Program: OutcomeNational HCV Treatment Program: Outcome
0.00%
50.00%
NEG POS
30.10%PERCENT
PCR RESULT
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50.00%
51.00%
52.00%51.40%
48.60%PERCENT
SUSTAINED VIRAL RESPONSE
National HCV Treatment Program: OutcomeNational HCV Treatment Program: Outcome
47.00%
48.00%
49.00%
50.00%
NEG POS
48.60%PERCENT
PCR RESULT
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� Governmental appreciation of the magnitude of HCV problem in Egypt
� National guidelines for treatment of chronic HCV
� MOH and universities cooperation
Different specialties cooperation� Different specialties cooperation
� Treatment for more than 145,000patients
� >90% governmental funding
� Data to answer a lot of questions
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� Stoppage rules
� Duration of therapy
� Cost effective analysis
� Non invasive detection of hepatic fibrosis � Non invasive detection of hepatic fibrosis
� Effect on disease progression
� Treatment of non responders
� HCV recurrence Post LTx
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� Quality control
� Individualization and personalization
� Funding
� Shortage of drugs� Shortage of drugs
� Stoppage rule
� Non responders
� No guidelines for special groups
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� National Committee for Control of Viral Hepatitis
� (Mostafa Kamal,Manal Hamdy,Nasr El Sayed,ArnaudFontanet, Gamal Esmat and Wahid Doss)
� Advisory Board for Management of HCV
� (Sherif AFattah, Shoukry Hunter, Ali Monis, AR El Zayadi, A D El Sehly, Seham A Rehim and A M Nasr)
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� Hepatitis C remains a major health problem in Egypt with 9% of the
population chronically infected .
� The national HCV control program has been effective in providing � The national HCV control program has been effective in providing
treatment nationwide for almost 145,000 patients.
� Methods for prevention of new infections need to be intensified.
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