HBV and HCV Epidemiology In Israel
Eli Zuckerman, Hedy S. Rennert, Gad Rennert .
Liver Unit and Department of Community Medicine and Epidemiology Carmel Medical Center,
Faculty of Medicine, Technion Haifa, Israel.
Disclosures
• Advisory boards (international): Merck • Consultant: Janssen, Merck, Roche • Advisory committees or review panels: Merck, Janssen • Speaker: Merck, Janssen, Roche, Novartis
HBV and HCV Epidemiology in Israel
• Epidemiological data of hepatitis B and hepatitis C virus infection in Israel is limited as large population-
based studies have not been performed so far.
• The aim of these studies was to collect epidemiological, co-morbidities and natural history data of HBV and HCV infection in the largest population-based study ever performed in Israel.
HBV and HCV Epidemiology in Israel
Methods
• Data were obtained from the computerized records and database of Clalit Health Services (CHS) (established in the year 2000). The database contains information regarding demographic parameters, laboratory tests and pharmacy records, hospitalization and primary care physician records and death-related data.
HBV Epidemiology in Israel
HBsAg positivity among CHS insured individuals
Age (yrs)
CHS
No. tested
% tested
No. pos
pos rate/100
All
3,843,868
870,124
22.6
15,258
1.75%
0-19
1,291,881
79,245
6.1
1181
1.45%
Prevalence HBV Infection in Israel
Age (yrs)
CHS
No. tested
% tested
No. pos
pos rate/100
All
3,843,868
870,124
22.6
15,258
1.75%
0-19
1,291,881
79,245
6.1
1181
1.45%
Prevalence HBV Infection in Israel
Age (yrs)
CHS
No. tested
% tested
No. pos
pos rate/100
All
3,843,868
870,124
22.6
15,258
1.75%
0-19
1,291,881
79,245
6.1
1181
1.45%
HBsAg Seropositivity rate per 100, by religion
0
0.5
1
1.5
2
2.5
3rate/100
כללי מגזר החרדים מגזר ערבי
כללימגזר החרדיםמגזר ערבי
Hepatitis B from lab results, n=15,240
1.48%
0.76%
2.98%
All Religious Jews Arabs
Prevalence HBsAg by Gender
Gender
CHS
No. tested
% tested
No. pos
pos rate/100
Male
1,929,822
340,059
17.6
9080
2.67%
Female
1,986,368
529,940
26.7
6174
1.16%
Age and sex distribution of HBsAg positives
59.6
40.4
7.7
20.5 22.3 20.0 16.8
8.03.4
1.30
10
20
30
40
50
60
%
Males Females 0-19 20-29 30-39 40-49 50-59 60-69 70-79 80+
age
0 1 2 3 4 5 6 7
Ethiopia
Tunisia
Moldova
Yemen
Russia
Algeria
Latvia
Ukraine
Israel
Iraq
Egypt
Germany
seropositivity rate/100 tested
Seropositivity rate/100, by country of birth - top 24 countries (% of population tested)
Hepatitis B from lab results, n=15,240
(21.8%)
(47.9%)
(19.8%)
(36.6%)
(40.6%)
(34.9%)
(24.3%)
(24.8%)
(20.3%)
(20.3%)
Romania
South America
Poland
India
Turkey
Belarus
Georgia
Lybia
USSR Moslem states
Syria
Morocco
Iran
0 0.5 1 1.5 2 2.5 3 3.5 4
50,000-99,999 לא יהודיים
20,000-49,999 לא יהודיים
10,000-19,999 לא יהודיים
לא יהודיים 2,000 - 9,999
ישוב כפרי אחר-לא יהודי
שבט בדואי
200,000+ יהודיים
100,000-199,999 יהודיים
50,000-99,999 יהודיים
20,000-49,999 יהודיים
10,000-19,999 יהודיים
יהודיים 2,000 - 9,999
ישוב כפרי אחר-יהודי
מושב
קיבוץ
seropositivity rate/100 tested
Seropositivity rate per 100, by type of settlement
Hepatitis B from lab results, n=15,240
Jews
Non-Jews
Seropositivity rate by type of settlement (577): ”top 15”
prevalence rate/tested
HBsAg +
% tested
No. tested
CHS population
יישוב
סמיע-כסרא 3844 1464 38 132 9 עין מאהל 9815 2784 28 228 8.1 סחנין 19200 5341 27 346 6.4 ירכא 7418 1602 21 94 5.9 ריינה 9131 2174 23.8 113 5.2 תמרה 25471 6137 24 310 5דנון' שייח 1970 374 19 19 5
סנאןאבו 6368 1589 25 77 4.8 אסד-דיר אל 5084 1303 25 52 4.6 כבול 8886 1353 15 63 4.6מנדאכפר 11886 4528 38 205 4.5 כרום דל'מג 13881 1198 8.6 54 4.5
דמיימה 249 127 51 13 10.2 אור יהודה 19906 5322 26 197 3.7
רמלה 25471 9541 21 358 3.75
Prevalence of HBcAb “only” (HBsAg-/ HBcAb +) and HBeAg
CHS
No. tested for both HBsAg and HBcAb
% tested
No. HBcAb only
pos rate/100
3,843,868
271458
31%
45527
17.5 %
CHS
No. tested for HBeAg
% tested
No. HBeAg postive
pos rate/100
3,843,868
12,475
82%
1136
9.1%
HBV co-infection with HCV and HDV
253/3574 435/13,550 32/3422
only 23% were tested for HDV
HBV Epidemiology in Israel: Summary
• This is the first and the largest epidemiological study on HBV infection ever performed in Israel.
• The estimated prevalence of chronic HBV infection in CHS insured individuals in Israel~ 1.75%. • The prevalence is higher in the Arabic population and in some rural Arabic settlements the prevalence of HBV infection may reach 5-9% .
HBV Epidemiology in Israel: Summary
• Further analysis of available data will explore more detailed information about virological status (HBeAg), HBV infection in the specific populations ( pediatric population, pregnant women, specific ethnic groups, patients with CRF etc.), treatment outcome, co-morbidities and natural history. • This data may assist in screening and planning treatment strategies in Israel.
HCV Epidemiology in Israel
HCV Epidemiology in Israel Source Population Sample size Prevalence Source
Flatau E, 1993
Jewish Ethiopian immigrants
200
3%
Stern M. 1995
Blood donors (Hadassah)
19,000
0.44%
82.7% PCR+,
28% risk factors (BT, IDU)
Bar-Shany S 1995
Blood donors
136,977
0.66%(M), 0.55% (F)
Prevalence higher in
immigrants from former USSR and eastern Europe
Gligberg F., 1997
Bukharian Jewish immigrants from
Tajikistan and Uzbekistan
102
26.5%
None of HCV+ had BT or were
IDU
Bogomolski-
Yahalom V 1997
HCV+ patients
and hemodialysis pts
63
Not relevant
HCV G1 65.5%
Shemer-Avni Y
1998
Blood donors from
Gaza strip
1509
2.2%
Most common genotype : 1b
HCV Epidemiology in Israel Source
Population
Sample size
Prevalence
Comments
Flatau E, 1993
Jewish Ethiopian
immigrants
200
3%
Stern M. 1995
Blood donors (Hadassah)
19,000
0.44%
82.7% PCR+,
28% risk factors (BT, IDU)
Bar-Shany S 1995
Blood donors
136,977
0.66%(M), 0.55% (F)
Prevalence higher in
immigrants from former USSR and eastern Europe
Gligberg F., 1997
Bukharian Jewish immigrants from
Tajikistan and Uzbekistan
102
26.5%
None of HCV+ had BT or were
IDU
Bogomolski-
Yahalom V 1997
HCV+ patients
and hemodialysis pts
63
Not relevant
HCV G1 65.5%
Shemer-Avni Y
1998
Blood donors from
Gaza strip
1509
2.2%
Most common genotype : 1b
HCV Epidemiology in Israel Source Population Sample size Prevalence Comments
Almog R, 1999
Immigrants from former USSR, candidates for military service
1182
1.3%
Prevalence
associated with COB
Sermoneta-Gertel S
2001
Health workers in
Hadassah hospitals in Jerusalem
4287
0.9%
Israeli born 0.1%, in Central Asia republics
of former USSR 5.7%.
Lurie Y 2006
Patients with acute
HCV infection
29
Not relevant
medical procedures-
65.5% IDU 20.6%
Maor Y, 2006
Hemophilic patients in one center born
before 1986
239
75%
87% were RNA +, G1 in 80% of HCV
Kerzman H 2007
Blood donors
434
Not relevant.
Case control study of
434 blood donors:
Loebstein R, 2008
Drug users
1443
35.7%
73.9% from eastern Europe and 19.6% of native Israelis were
HCV positive
HCV Epidemiology in Israel Source Population Sample size Prevalence Comments
Almog R, 1999
Immigrants from former USSR, candidates for military service
1182
1.3%
Prevalence
associated with COB
Sermoneta-Gertel S
2001
Health workers in
Hadassah hospitals in Jerusalem
4287
0.9%
Israeli born 0.1%, in Central Asia republics
of former USSR 5.7%.
Lurie Y 2006
Patients with acute
HCV infection
29
Not relevant
medical procedures-
65.5% IDU 20.6%
Maor Y, 2006
Hemophilic patients in one center born
before 1986
239
75%
87% were RNA +, G1 in 80% of HCV
Kerzman H 2007
Blood donors
434
Not relevant.
Case control study of
434 blood donors:
Loebstein R, 2008
Drug users
1443
35.7%
73.9% from eastern Europe and 19.6% of native Israelis were
HCV positive
HCV Epidemiology in Israel
Data from Magen David Adom (MDA):
• Seroprevalence of HCV among all blood donors (BD) in 2000 was 0.1% (240 of 220,000)
• 0.8% (168/22000) among immigrants (BD) from the former USSR in 1990s
• 0.04% (72/198,000) detected among native Israeli BD.
Prevalence HCV Infection in Israel
• CHS insured individuals: 3,926,182 (including children)
• Age >20 y/o: 2,658,885
• Tested for HCV infection: 789,689 (20.1%) age >20: (29.7%)
• 18406 were HCV+: 2.3% • 3067 died prevalence 1.96%
Seropositivity rate per 1,000, by country of birth - top 20 countries (% of population tested) (14.7%-32.8%)
0 10 20 30 40 50 60
Georgia
Turkmenistan
Moldova
Uzbekistan
Ukraine
Kazakhstan
Russia
Tajikistan
Azerbaijan
Kirghizstan
USSR
Belarus
Latvia
Romania
Lithuania
Morocco
Italy
Canada
Egypt
Brazil
seropositivity rate/1,000Hepatitis C from lab results, n=18,406 10/2010
(30.5%)
(29.5%)
(17.4%)
(21.1%)
(29.0%)
Age distribution – HCV vs CHS
0
5
10
15
20
25
%
20-29 30-39 40-49 50-59 60-69 70-79 80+
HCVCHS
Mean age HCV: 48.9 (SD 17.48)
Hepatitis C from lab results, n=18,406, 10/2010
HCV in Israel
HCV in Israel: Distribution By religion
0
20
40
60
80
100
%
Jews Arabs
HCVCHS
n=884
n=17,156
Hepatitis C from lab results, n=18,406, 10/2010
HCV in Israel: Distribution By Gender
0
10
20
30
40
50
60
70
%
males females
HCVCHS
n=7065
n=10,975
Hepatitis C from lab results, n=18,406, 10/2010
% of HCV pts with selected comorbidities
14.1
11
7.2
0.6
0
2
4
6
8
10
12
14
16
Diabetes Obesity Hepatitis B HIV
Hepatitis C from lab results, n=18,406, 10/2010
92.9% had HBsAg test
Top causes of death in HCV pts and Israel (not only CHS)
2.125.79
2.951.45
3.073.19
3.460.11
3.687.05
4.078.11
5.184.71
5.910.59
8.70.53
0 1 2 3 4 5 6 7 8 9%
MI
chronic renal failure
lung ca
overdose
cerebral vascular
IHD
diabetes
cirrhosis of liver
liver ca
Israel
HCV
Hepatitis C from lab results, n=18,406 10/2010
Top causes of death in HCV pts and Israel (not only CHS)
2.125.79
2.951.45
3.073.19
3.460.11
3.687.05
4.078.11
5.184.71
5.910.59
8.70.53
0 1 2 3 4 5 6 7 8 9%
MI
chronic renal failure
lung ca
overdose
cerebral vascular
IHD
diabetes
cirrhosis of liver
liver ca
Israel
HCV
Hepatitis C from lab results, n=18,406 10/2010
HCV-RNA (PCR) testing in HCV-positive patients in Israel
63.0
38.5
30.8
0
10
20
30
40
50
60
70
%
PCR RNA-genotype RNA-quantitative
Hepatitis C from lab results, n=18,406 10/2010
PCR results
75.5
24.5
01020304050607080
%
positive negative
Hepatitis C from lab results, n=18,406 10/2010
HCV genotypes
Type 42%
Type 170%
Type 320%
Type 28%
Hepatitis C from lab results, n=18,406, 10/2010
HCV genotypes by country of birth (n=5,364)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Iraq
Yemen Ira
n
Moroc
coEgy
pt
Ethio
pia
USSR <19
89
Belaru
s
Ukrain
e
Russia
Moldov
a
Georg
ia
Azerb
aijan
Kazak
hstan
Uzbek
istan
Poland
Roman
ia
Argen
tina
Israe
l
4321
Number of HCV cases diagnosed by year
Rate of HCV Patients Who Received Treatment (overall: 1739/18,040 = 9.6%)
9.8 9.3 9.7 9.2
4.7
7.1
11.2
7.8
0
2
4
6
8
10
12
%
males females Jews Arabs Asia Africa Eur-Amer
Israel
Country of birth (Jews) Up to 300 pts received treatment in clinical trial, not thru CHS
HCV Epidemiology in Israel 2001-2010
• % of HCV patients Treated with Anti-Viral therapy
• Total: 1739 + 300 (clinical trials) = 2039 • HCV+ patients: 18,406 • ~ 30%-40% are not eligible for treatment
• Actual estimated treatment rate: ~ 16%-18%
Time from diagnosis to treatment
0
10
20
30
40
50
60
70
%
0-3 3-6 6-12 >12 Months
SVR in treated patients: all genotypes (n=1423)
62.4
37.6
0
10
20
30
40
50
60
70
%
SVR no SVRData on 1423 patients with treatment and follow-up lab test
Percent SVR by genotype
53.3
82.2 74.9
25
0102030405060708090
%
1 2 3 4genotype
HCV Epidemiology in Israel: Summary
• This is the first and the largest epidemiological study on HCV infection ever performed in Israel.
• The estimated prevalence of chronic HCV infection in Israel is ~ 2%. • The prevalence was associated with country of origin
and was as high as >4% in some countries of the former USSR.
• PCR was positive in 75.5% and the most frequent genotype was genotype1 (70%).
HCV Epidemiology in Israel: Summary
• Less than 20% of the eligible candidates were treated.
• In more than 60%, time elapsed from diagnosis to initiation of treatment was > 12 months.
• Overall 62.4% achieved SVR (53.3% G1 patients). • More efforts should be directed to increase the
number of diagnosed and treated patients.