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.