EPIDEMIOLOGY, BURDEN AND PREVENTION

OF HBV AND HCV

- December 2016-

ANGELOS HATZAKIS, MD
PROFESSOR OF EPIDEMIOLOGY & PREVENTIVE MEDICINE
ATHENS UNIVERSITY MEDICAL SCHOOL

GEORGE PAPATHEODORIDIS, MD
PROFESSOR IN MEDICINE AND GASTROENTEROLOGY
ATHENS UNIVERSITY MEDICAL SCHOOL

HARRY JANSSEN, MD
PROFESSOR OF MEDICINE, TORONTO WESTERN AND TORONTO GENERAL HOSPITAL,
UNIVERSITY HEALTH NETWORK, TORONTO, CANADA
 CONTENTS (1)
 Background

 Burden of HBV, HCV Infections

Prevalence, Incidence, Surveillance

 Complications and Natural History

 Burden of HBV, HCV Disease

Cirrhosis, HCC, Liver transplantation

 Global Burden in People Who Inject Drugs (PWID)

Prevalence of HBsAG, Anti –HCV, HIV/HCV, HCV co-infections

 HBV Vaccination

 Prevention of Hepatitis Caused by Drug Use Behaviors

 Prevention of Health Care Associated Hepatitis

 Screening of HBV and HCV

BACKGROUND
Hepatitis Epidemic Profile: Burden and Response

Burden of infection (who, where, when)

 Incidence: new hepatitis infections per year
 Prevalence: number of hepatitis infection at a specific time
point
Burden of disease (who, where, when)
 Incidence/Prevalence of clinical events (acute hepatitis,
cirrhosis, HCC)
 Deaths and mortality
Response (efficacy, coverage, effectiveness)
 Prevention services
 Treatment
Hatzakis A et al. 2014
Wiktor S et al. 2014
 HBV Facts (1)

Hepatitis B virus (HBV) attacks the liver and can cause both
acute and chronic disease.
The virus is transmitted through contact with the blood or
other body fluids of an infected person.
HBV is 50-100 times more infectious than HIV.
HBV can survive outside the body for at least 7 days.
HBV is an important occupational hazard for health workers.
Hepatitis B is preventable with a safe and effective vaccine.

WHO HBV Facts Sheet 2008

 HBV Facts (2)

Common modes of transmission include:

 Perinatal (from mother to baby at birth)

 Early inapparent childhood infections (close contact with

infected individuals)
 Unsafe injection practices

 Blood transfusions

 Sexual contact

 Injecting drug use

 Occupational exposure of health care workers

WHO HBV Facts Sheet 2008

 HCV Facts (1)
Hepatitis C virus (HCV) attacks the liver and can cause both acute
and chronic disease.
HCV is transmitted through contact with the blood of an infected
person.
HCV can remain infectious in dried blood samples for 16 hours.
HCV infection is curable using increasingly effective antivirals.
Currently, no vaccine is available to prevent HCV infection.
Among HCV infected, 50-80% will develop chronic infection;
among chronically infected up to 50% will develop cirrhosis
(scarring of the liver) and 1-5% liver cancer within 20-30 years.

WHO HCV Facts Sheet 2011

MacCannel T et al. Clin Liver Dis, 2010; 14: 23
 HCV Facts (2)
Transmission of HCV can occur:
 Receipt of contaminated blood transfusions, blood products and
organ transplants.
 Injections with contaminated syringes.

 Needle-stick injuries in health care settings.

 Injection drug use.

 Being born to an HCV infected mother.

 Sexual contact (less common).

 Sharing personal items contaminated with infectious blood (less

common).

WHO HCV Facts Sheet 2011

MacCannel T et al. Clin Liver Dis, 2010; 14: 23
Prevalence, Incidence, Surveillance

BURDEN OF HBV, HCV INFECTIONS

 Burden of infection and disease of HBV and HCV
HBV HCV HIV
Chronic infections worldwide 240m 188m 35.3m
(WHO)
Chronic infections in 13.3m 15m 2,2m
European Region (WHO)
Mortality (deaths/year) 786,000 499,000 1,6m
worldwide
Mortality (deaths/year) in 36,000 86,000 66,000
WHO European Region

Global Burden of Disease Study 2010. Lozano et al, Lancet 2012

Global HBsAg endemicity (1957-2013)

Schweitzer A et al, 2015

 HBsAg Seroprevalence and the number of people living with Chronic
Hepatitis B in the general population by WHO region
Prevalence estimates HBsAg-positive population
(%,95% CI)

WHO African Region 8.83% (8.82-8.83) 75.641.609

WHO Region of Americas 0.81% (0.81-0.81) 7.622.334

WHO Eastern 3.01% (3.01-3.01) 17.409.688

Mediterranean Region

WHO European Region 2.06% (2.06-2.06) 18.486.179

WHO South East Asian 1.90% (1.90-1.90) 34.000.099

Region

WHO Western Pacific Region 5.26% (5.26-5.26) 95.270.570

Total (2010) 3.61% (3.61-3.61) 248.000.000

Schweitzer A et al, 2015

Geographical distribution of the HBV genotypes and sub-genotypes

Locarnini S et al. J Hepatol 2015. 62, 1 (S76-86)

HBV in China (1)

Liu J et al, 2015

HBV in China (2)

Liu J et al, 2015

Updated published estimates, an aging population and a focus on
viremic infections contribute to a lower estimated viremic
prevalence
Loss due to more recent estimates for
India and China, and the impact of
time (mortality)

240
Viremic Rate of 70%
200
Updated estimate for Nigeria, impact
of time, 500k cured patients in 2015
160
Total Cases (M)

120

80

40

0
Anti-HCV, 2005 Anti-HCV, 2013 HCV-RNA, 2013 HCV-RNA, 2016
(Mohd Hanafiah (Gower 2014) (Gower 2014) (Present
2013) Analysis)

In the present analysis, all available data were adjusted for viremia, and the populations
were aged to 2016 to account for mortality

Razavi H, 2016
 An estimated 70 million (56 million – 90 million) individuals are
infected with HCV (viremic), a prevalence of 1% (0.8%-1.2%) in 2016

Prevalence
(Viremic)
0.0%-0.6%
0.6%-0.8%
0.8%-1.3%
1.3%-2.9%
2.9%-6.7%

Total Infected
250,000

3,000,000

6,000,000

In 2015, 500K patients were treated and

cured with DAAs.

Source: Polaris Observatory (http://www.polarisobservatory.com/) Razavi H, 2016

 Genotype Distribution by Region
North America Europe, Western Europe, Central Europe, Eastern Asia, Central Asia Pacific, High Income Asia, South

Caribbean Asia, Southeast

Latin America, Central Asia, East

Prevalence (Viremic) Australasia

Latin America, Tropical
0.0%-0.6%
0.6%-0.8%
0.8%-1.3%
1.3%-2.9%
2.9%-7.8%

Latin America, Southern Latin America, Andean North Africa/Middle East Sub-S Africa, Central Sub-S Africa, Southern Sub-Saharan Africa, West

22
Razavi H, Gower E, Estes C, Hindman S. Global HCV Genotypes. Poster presented at: AASLD: The Liver Meeting 2013; 2013 Nov 1-5; Washington, DC, United States.
Hepatitis B prevalence in the general population of Europe: HBsAg

<0.5
0.5 - <1
1 - <2
2 - <4
4 - <6
6 - <8
≥8
No recent data
Not included in review

Non-visible countries

Liechtenstein
Luxembourg
Malta

ECDC Technical Report, September 2010

Hepatitis C prevalence in the general population of Europe: Anti-HCV

<0.5
0.5 - <1
1 - <2
2 - <4
4 - <6
6 - <8
≥8
No recent data
Not included in review

Non-visible countries

Liechtenstein
Luxembourg
Malta

ECDC Technical Report, September 2010

Estimated number of HBsAg-positive individuals by country,
based on general population prevalence estimates

4000000

3500000

3000000

2500000

2000000

1500000

1000000

500000

ECDC Technical Report, September 2010

Estimated number of anti-HCV positive individuals by European
country, based on general population prevalence estimates

4000000

3500000

3000000

2500000

2000000

1500000

1000000

500000

ECDC Technical Report, September 2010

 Burden of HBV, HCV in non-EU Mediterranean Countries (1)
Algeria Egypt Israel Jordan
Population 36.3 million 84 million 7.7 million 6.5 million
(2011)
HBsAg HCVAb HBsAg HCV Ab HBsAg HCV Ab HBsAg HCV Ab
General 2.15% n/a 1.6% 14.7% 1.96% 9.9%
population (1998) (2003) (2008) (2001–10)
Blood donors 0.88% 0.21% 16.8% 0.1% 0.05% 0.7–1.5%
(2010) (2010) (2011) (2011) (2011) (2008)

Haemodialysis 10.5% 23.8% 46% 18% 5.9% 24.5-30.5%

(2008) (2008) (1994) (2000) (2008) (2008)

Injecting drug 3.5% 35.7%

users (2008) (2003–5)
Health-care 1.5% 16.4% 17.6% (HBc+) 1.5%
workers (2011) (2011) (1992)

Pregnant 1.8% 0.3% 4% 6.4% 1.7% (2005) 4.3%

women (1998) (1997) (2010) (2010) (0.66% in (2001)
Jewish and
2.84% in Arab
populations)

EU, European Union; HBsAg, hepatitis B surface antigen; HCV Ab, antibody against hepatitis C virus

Hatzakis A et al. JVH 2013

Burden of HBV, HCV in non-EU Mediterranean Countries (2)
Lebanon Libya Morocco Tunisia
Population 6 million 32.3 million 10 million
HBsAg HCV Ab HBsAg HCV Ab HBsAg HCV Ab HBsAg HCV Ab
General 1.69% 0.2% 2.2% 1.3% 0.75 - 1.5% 3% 4% - 5.7% 0.2 -1.7%
population (2011) (2011) (2013) (2013) (2009) (1996) (1996)

Blood donors 0.7% 0.23% 1.3% 1.87% 0.4 – 0.7%

(2007) (2007) (2005) (2011) (2011)

Haemodialysis 2.62% 13% 19.5% 39%

(2007) (2005) (2006)

Injecting drug 0.0-2% 52% 30%

users (2003-7) (2010) (2011)

Health care 0.4% 2 – 7%

workers (1999) (2003)

Pregnant 2.9% 0% 2.7% 4%

women (1997) (1997) (2003) (2010)

EU, European Union; HBsAg, hepatitis B surface antigen; HCV Ab, antibody against hepatitis C virus

Hatzakis A et al. JVH 2013

Burden of HBV, HCV in non-EU Mediterranean Countries (3)
Herzogovina Croatia Kosovo Servia

Population 3.8 million 4.4 million 1.7 million 7.2 million

HBsAg HCV Ab HBsAg HCV Ab HBsAg HCV Ab HBsAg HCV Ab

General Incidence 0.29–0.89% 1.5% 1.3% 2% 1.5%

population reports only (2011) (2005) (2005) (no date) (no date)

Blood donors 0.29% 0.09% 0.07% 4.2% (2009) 0.29%

(2011) (2010) (2010) (2009)
Haemodialysis 58.9% <1% 8.4% 12% (2009) 43%
(2006) (2009) (2009) (2009)
Injecting drug 35% 0.63% 41% 37% 45–69%
users (2006) (2008) (2008) (2011)
Health care 0.4%
workers (2006)
Pregnant women 0.22% 0.5%
(2011) (2011)

EU, European Union; HBsAg, hepatitis B surface antigen; HCV Ab, antibody against hepatitis C virus

Hatzakis A et al. JVH 2013

 Impact of immigration
Estimated proportion of HBsAg prevalence attributable to immigration
Estimated HBV Proportion of
Estimated
prevalence in HBV prevalence
overall HBV
Country Author indigenous attributable to
prevalence
populations immigration
[b]
[a] [(b-a)/b]

France Cazel et al. 1976 0.44% 0.56% 22%

Sweden* Christenson et al. 1997 2.00% 2.74% 27%

Sweden** Lindh et al. 1993 0.02% 0.11% 81%

Denmark Gjorup et al. 2003 0.03% 0.15% 80%

Netherlands*** Kretzschmar et al. 2002 0.002% 0.03% 94%

*Note that this prevalence is for the presence of anti-HBc- not specific to HBSAg marker
** Carriage was defined as HBsAg positivity in serum for at least 6 months
***Prevalence of HBV carrier estimated using mathematical model

Cazel P et al. Revue Francaise de Transfusion et Immuno-hématologie 1976;19(4):569.

Christenson B et al, Epidemiol Infect. 1997;119(2):221.
Lindh M et al. J Infect Dis. 1997;175(6):1285.
Gjorup IE et al. Scand J Infect Dis. 2003;35(4):260.
Kretzschmar M et al. Epidemiol Infect. 2002;128(2):229.
 Estimated number of HBsAg- and anti-HCV-positive individuals
in the largest migrants groups, by European country

120000

HBsAg positive
100000
Anti-HCV positive

80000

60000

40000

20000

*no data on anti-HCV prevalence

ECDC Technical Report, September 2010

Estimated number of HBsAg- and anti-HCV-positive individuals in
the largest migrants groups, by country

ECDC Technical Report, September 2010

 Parameters of Treatment Cascade
in European Union 2015
3,500,000
3,207,000

3,000,000

2,500,000

2,000,000

1,500,000
1,174,000

1,000,000

500,000
162,000 144,000
-
Viremic Diagnosed Newly Cured
Infections Treated

Razavi H et al, 2016

 HCV prevalence and total infected
in the European Union

Prevalence
(Viremic)

0.0%-0.56%
0.56%-0.75%
0.75%-1.3%
1.3%-2.95%

Total Infected

700,000
10,000

Razavi H et al, 2016

 European Union viremic infections
by age cohort, 2015

Total Viremic Infections by Age Cohort (2015)

450,000
400,000
350,000
300,000
Cases

250,000
200,000
150,000
100,000
50,000
-

Razavi H et al, 2016

 Total viremic HCV infections, by country, 2015

Total Viremic Infections by Country (2015)

2,000,000

1,500,000 80% of all HCV infections

Cases

1,000,000

500,000

Razavi H et al, 2016

 HCV Prevalence and Genotype Distribution - Europe
United Czech
Ireland Kingdom Norway Denmark Sweden Finland Hungary Republic Slovakia Poland Lithuania Latvia

Belarus Russia
France Switzerland Germany Austria Netherlands

Serbia Romania
Belgium Luxembourg

Georgia Estonia

Prevalence Total Infected

(Viremic) (Viremic)
0.0%-0.6% 0-200K
200K-650K
0.6%-0.8% Turkey Armenia
0.8%-1.3% 650K-1.9M

1.3%-2.9%
1.9M-3.5M
2.9%-7.8%
Bosnia &
Portugal Spain Italy Greece Slovenia Croatia Herzegovina Montenegro Albania Macedonia

37
Gower, E., Estes C., Hindman, S., Razavi-Shearer, K., Razavi, H. Global epidemiology and genotype distribution of the hepatitis C virus. Journal of Hepatology 2014.
COMPLICATIONS AND NATURAL HISTORY
 Complications (1)
The risk of developing chronic hepatitis B infection after acute exposure
Mode of Age of Risk of Acute Risk of chronic Lifetime risk
transmission infection Icteric HBV infection of HCC*
Hepatitis
Perinatal HBeAg- Birth <1% 90% 15%-40%
positive mother
Perinatal HBeAg- Birth 5% <15% 15%-40%
negative mother
Horizontal Between birth <10% 50% 15%-40%
and age 2 years
Horizontal 2-5 years 9% 30% 15%-25%
Horizontal 5-10 years 10% 16% 15%-25%
Horizontal >10 years 10%-33% 7%-14% Unknown

* In those with chronic HBV infection

McMahon BJ. Clin Liver Dis 2010; 14: 381

 Complications (2)
Incidence of liver cirrhosis and HCC depending on phase of HBV infection
Phase of infection Liver cirrhosisa HCCa
(per year) (per year)

1. Immune tolerant Rare Rare

2. HBeAg-positive CHB (immune reactive) 2.4-3.5% 3-6% in those
with cirrhosis
3. Low replicative Rare if remain in 0.06%b
this phase
4. HBeAg negative 2.1-2.9% 3-6% in those
with cirrhosis
5. HBsAg negative Rare 0.02%b

a Assuming no co-existent liver pathology

b Substantially higher than in background uninfected population

Alter MJ. Hepatology, 2003; 39: 564

Chen JD. Gastroenterology, 2010;138:1747
Aspinalli EJ et al. Occup Med 2011; 61:531
 Complications (3)

Spontaneous Clearance of HCV-RNA

Group Rate (95%CI)

HIV+MSM 15.4%(11.5-19.3)

PWIDs 24.3%(19.5-29.1)

Smith DJ, 2016

 Complications (4)
Natural history of hepatitis C from retrospective, prospective and
retrospective-prospective cohort studies (A)
Retrospective studies
Intervals from exposure 9-29 years
Cirrhosis 17-55% (mean 42%)
HCC 1-23%
Liver deaths 4-15%
Prospective studies
Intervals from exposure 8-16 years
Cirrhosis 7-16% (mean 11%)
HCC 0.7-1.3%
Liver deaths 1.3-3.7%

Seef LB. Hepatology, 2002;36:535.

Hatzakis A et al. JVH, 2011;18:S1
 Complications (5)
Natural history of hepatitis C from retrospective, prospective and
retrospective-prospective cohort studies (B)
Retrospective -Prospective Cohort Studies
Children and young men or women
Exposure interval 9-45 years
Cirrhosis 0.3-5.9% (mean 2.1%)
HCC 0
Liver deaths 0-2.1%
Middle-aged people with post-transfusion hepatitis
Exposure interval 23 years
Cirrhosis 15%
HCC 1.9%
Liver deaths 2.8%

Seef LB. Hepatology, 2002;36:535.

Hatzakis A et al. JVH, 2011;18:S1
 Complications (6)

Risk of selected EHMs in HCV infected patients compared to

those without HCV

Younossi Z et al, 2016

 Complications (7a)

Recurrent of HCV RNA after sustained virological report response. This could result
from either (A) late relapse of a majority variant, (B) persistence/re-emergence of a
pre-existing minority variant, or (C) reinfection with a new viral strain. TW0,
treatment week 0; E0T, end of treatment; SVR,
sustained virological response; LOD; level of detection

Midgard H et al, 2016

 Complications (7b)

Differences in hepatitis C epidemiology among people who

inject drugs and men who have sex with men

Midgard H et al, 2016

Cirrhosis, HCC, Liver transplantation

BURDEN OF HBV, HCV DISEASE

 Hepatocellular Carcinoma (HCC) worldwide

 Fifth most common cancer in men and seventh most

common cancer in women.

 Third leading cause of cancer-related deaths.

 Most of burden of disease (85%) is borne in developing

countries.

 Major risk factors are HBV and HCV.

El-Serag HB. N Engl J Med 2011;365:1118

Regional variation in the estimated age-standardized incidence
rates of liver cancer

El-Serag HB. N Engl J Med 2011;365:1118

 Estimates of the attributable fraction of hepatocellular
carcinoma due to infection with HBV or HCV, by WHO region

Perz JF et al. J Hepatol, 2006;45:529

(A) Estimated age-standardized incidence rates of liver cancer per 100,000 in
2008; WHO, GLOBOCAN, 2008. (B) Estimated age-standardized mortality
rates per 100,000 for liver cancer in 2008; WHO, GLOBOCAN, 2008

Blachier M et al. J Hepatol, 2013; 58,3: 593 - 608

 Europe: estimated HCV- and HBV-related HCC mortality rate
per 100,000 men and women by country

4.5 HCV men

HCV women
4
HBV men
3.5 HBV women
3
Estimated mortality
rate/100,000

2.5

1.5

0.5

ECDC Technical Report, September 2010

Europe: estimated HBsAg and anti-HCV prevalence in HCC
patients, by country

70 Anti-HCV
HBsAg
60

50
Prevalence (%)

40

30

20

10

ECDC Technical Report, September 2010

 Age-standardized death rates per 100,000 population from liver
cirrhosis in European countries, males and females aged 20–64; WHO
mortality database 2000–2002

Blachier M et al. J Hepatol, 2013; 58,3: 593 - 608

Changing trends in hepatitis C–related mortality in the United
States, 1995‐2004

Wise M et al. Hepatology, 2007; 47: 4, 1128

Changing trends in hepatitis C–related mortality in the United
States, 1995‐2004

Wise M et al. Hepatology, 2007; 47: 4, 1128

Age-adjusted incidence and 5-year survival rates for patients with hepatocellular
carcinoma in the United States, 1973–2007

El-Serag HB. N Engl J Med 2011;365:1118

The prevalence of HCC stratified by risk factors (NAFLD,
alcohol, abuse, HCV and HBV) over time in a US
Veterans Affairs Population

Thrift A et al, 2016

 Trends in the prevalence and incidence of cirhossis and in the number of deaths
among patients with cirhossis between 2001 and 2013 in the VA health care
system, presented for all patients and separately for patients with HCV, ALD, or
NAFLD. ALD, alcoholic liver disease; HCV, Hepatitis C virus; NAFLD, non-alcoholic
fatty liver disease

Beste L et al, 2015

 Trends in incidence of HCC and in the number of deaths among patients with HCC
between 2001 and 2013 in the VA health care system, presented for all patients and
separately for patients with HCV, ALD, or NAFLD. ALD, alcoholic liver disease; HCV,
Hepatitis C virus; NAFLD, non-alcoholic fatty liver disease

Beste L et al, 2015

Welzel TM et al, 2013
 Primary indications for liver transplantation in Europe
among patients with cirrhosis, 1988-2009

Unknown
Secondary biliary cirrhosis 1% 7%

Autoimmune hepatitis 4%

Primary biliary cirrhosis

10%

40% Viral hepatitis

Viral hepatitis +
5%
Alcohol

33%
Alcohol
EASL – Blachier M et al. 2013
Primary indications for liver transplantation in Europe
among patients with viral hepatitis, 1988-2009

HBV+HCV HBV+HDV+HCV
4% 1%
HBV+HDV 8%

HBV 24%

63% HCV

EASL – Blachier M et al. 2013

Prevalence of HBsAG, Anti –HCV, HIV/HCV, HCV co-infections
GLOBAL BURDEN IN PEOPLE WHO INJECT
DRUGS (PWID)
Global estimates of HBsAg prevalence in IDUs

Nelson PK et al. Lancet 2011; 378

Global estimates of anti-HCV prevalence in IDUs

Nelson PK et al. Lancet 2011; 378

 Regional and global estimates of anti-HCV and HBsAg infected IDUs
Estimated number of IDUs
anti-HCV positive
Mid (range)
Eastern Europe 2.346.000 (1.244.500-3.918.000)
Western Europe 727.500 (497.000-1.018.000)
East and Southeast Asia 2.642.000 (1.820.000-3.576.500)
South Asia 354.500 (232.500-532.000)
Central Asia 146.000 (91.500-213.000)
Caribbean --
Latin America 1.022.000 (675.500-1.441.000)
Canada and USA 1.673.500 (1.099.000-2.471.500)
Pacific Island states & territories --
Australia and New Zealand 97.000 (44.500-165.000)
Middle East and North Africa 63.500 (28.500-115.500)
Sub-Saharan Africa 800.000 (206.500-1.524.000)
Extrapolated global 10.018.000 (6.031.000-15.186.500)
Estimated number of IDUs
HBsAg positive
Mid (range)
280.000 (100.000-543.000)
54.000 (13.500-108.500)
340.000 (111.000-696.000)
71.500 (20.000-154.500)
21.500 (6.000-46.000)
--
43.500 (12.500-90.500)
272.500 (57.500-642.000)
--
7.000 (3.000-12.000)
14.000 (7.500-26.500)
106.500 (11.500-296.500)
1.229.000 (346.500-2.654.500)
Nelson PK et al. Lancet, 2011; 378
Estimated number anti-HCV and HBsAg infected IDUs

HBsAg (+) anti-HCV (+)

Eastern Europe
Western Europe
East & Southeast Asia
South Asia
Central Asia
Latin America
Canada & USA
Australia & New Zealand
Middle East & North Africa
Sub-Saharan Africa

0 500000 1000000 1500000 2000000 2500000 3000000

Nelson PK et al. Lancet, 2011; 378

 Global epidemiology of HBV and HCV in IDUs

 Global estimate of IDUs: 16 (11-21) m

 HCV Prevalence in IDUs: 20-90%
 Global estimate of HCV infected IDUs: 10.0 (6.0-15.0) m
 HBsAg prevalence in IDUs: 0-20%
 Global estimate of HBsAg positive IDUs: 1.23 (0.35-2.65) m
 Global estimate of HCV infected: 130-170 m
 Global estimate of chronic HBV: 350 m
 HCV/HIV coinfected
 Reinfection of HCV

Nelson PK et al. Lancet 2011; 378

Proportion of total burden of HIV attributable to
injecting drug use by country, 2013

Degenhardt L et al, 2016

 Proportion of total burden of hepatitis C virus
attributable to injecting drug use by country, 2013

Degenhardt L et al, 2016

 Proportion of total burden of hepatitis B virus
attributable to injecting drug use by country, 2013

Degenhardt L et al, 2016

Global Epidemiology of HIV/HCV co-infection (1)

Platt l et al, 2016

 Global Epidemiology of HIV/HCV co-infection (2)

Meta-analysis of odds of HCV antibody in selected HIV-positive

populations versus HIV-negative population groups

Platt l et al, 2016

Global Epidemiology of HIV/HCV co-infection (3)

Platt l et al, 2016

HBV VACCINATION
 HBV vaccine Facts (1)

A. 1st gen – Plasma derived (1981)

2nd gen – Recombinant DNA vaccine (1986)
3rd gen – Triple antigen vaccine (1992)
B. Efficacy: 95-100%, <90% in immunocompromised
C. Vaccination schedule: 1, 2, 6 months
D. Booster dose: No booster up to 20 years
E. Safety: Excellent

Zanetti AR et al. Vaccine, 2008; 26:6266

WHO-Europe Facts, 2012
 HBV vaccine Facts (2)

F. WHO, 1991: All countries should introduce universal HBV

vaccination into national immunization programmes
G. Worldwide, 2010: Estimated coverage of fully vaccinated infants:
75%.
Countries integrated HBV vaccine: 92%
H. Europe, 2009: 46 out of 53 countries implement universal HBV
immunization, 6 countries implement immunization of high risk
sexual and IDU adults.

Zanetti AR et al. Vaccine, 2008; 26:6266

WHO-Europe Facts, 2012
Hatzakis A et al. JVH 2011; 18, S1
prevalence of positivity of chronic hepatitis b infection related seromarks including HBsAg,
anti HBc and HBeAg by age and gender among residents aged 15 years and older who
participated in the national survey in Taiwan, 2002

Chen CL et al, 2015

PREVENTION OF HEPATITIS CAUSED
BY DRUG USE BEHAVIORS
 WHO, UNODC, UNAIDS guidance for universal access of
IDUs to HIV prevention, treatment and care

1. Needle and syringe programmes (NSPs).

2. Opioid substitution therapy (OST) and other drug dependence
treatment.
3. HIV testing and counseling (T&C).
4. Antiretroviral therapy (ART).
5. Prevention and treatment of sexually transmitted infections (STIs).
6. Condom programmes for IDUs and their sexual partners.
7. Targeted information, education and continuation (IEC) for IDUs and
their sexual partners.
8. Vaccination, diagnosis and treatment of viral hepatitis.
9. Prevention, diagnosis and treatment of tuberculosis (TB).

WHO, UNODC, UNAIDS, 2009

Interventions for prevention and control of infectious
diseases in IDUs

ECDC, EMCDDA, 2011

ECDC, EMCDDA, 2011
PREVENTION OF HEALTH CARE
ASSOCIATED HEPATITIS
 Health care associated hepatitis (1)

 Patient to patient transmission

 Breaches of infection control and unsafe health care practices

 Patient to provider transmission

 Sharps injuries

 Transfusion of infected blood and blood products

 Transplantation of infected organs

 Health care associated hepatitis (2)

 Patient to patient transmission

Breaches of infection control and unsafe health care practices include:

1. Syringe and needle reuse

2. Vial contamination

3. Improper use and handling of blood glucose monitoring equipment

4. Lapses in the reprocessing of patient equipment (e.g. endoscopes)

5. Contamination of equipment, supplies and the environment

Perz JF et al. Clin Liver Dis, 2010;14:137

 Health care associated hepatitis (3)

1. Syringe and needle reuse

 Injection equipment reuse is negligible in developed world.

 In developing world persons receive 3.4 injections/year of which 39.8%

with reused equipment.

 Unsafe injection practices is the cause of 31.9% (0.9-58.3%) of HBV

infections, 39.9% (0.9-81.7%) of HCV infections and 5.4% (0-24.3%) of HIV
infection in developing world.

 In 2000, contaminated injections caused 21million HBV, 2million HCV and

260.000 HIV infections.

Hauri AM et al. Int J STD AIDS, 2004; 15:7-16

Number of injections per person and per year and proportion of these administered
with injection equipment reused in the absence of sterilisation,
by region, 2000

Hutin Y J F et al. BMJ 2003;327:1075

HIV infections transmitted through unsafe
injections, in 2000 and 2010

Pepin J et al, 2014

HCV infections transmitted through unsafe
injections, in 2000 and 2010

Pepin J et al, 2014

HBV infections transmitted through unsafe
injections, in 2000 and 2010

Pepin J et al, 2014

 Health care associated hepatitis (4)

 Patient to provider transmission

 Worldwide 35million health care personnel suffer 16.000 HCV and

66.000 HBV infections annually.
 Risk of HBV infection after percutaneous exposure is 23-62%,
dependent of e antigen status and HBV-DNA levels of the source.
 HBV can remain infective in the environment for more than 7 days.
 Risk of HCV infection after percutaneous exposure is 1.8%.
 HCV in dried blood samples can remain infective in the environment
for 16 hours.

MacCannel T et al. Clin Liver Dis, 2010; 14: 23-36

 Prevention of health care associated hepatitis (1)

 Awareness, understanding, implementation and enforcement of

best practice guidelines.
Remain suboptimal.

 Hierarchy of controls to establish priorities for hazard reduction

in the workplace.
Remain suboptimal.

 HBV vaccination of health care personnel.

Remain suboptimal.

Hatzakis A et al, 2012

 Prevention of health care associated hepatitis (2)

 Recognition and containment of health care associated

hepatitis.
Remain suboptimal.

 Screening of blood for prevention of transfusion and

transplantation associated hepatitis by serology and nucleic acid
testing (NAT).
Highly successful in developed world.

Hatzakis A et al, 2012

Prevention of health care associated hepatitis in the US

Estimated incidence and residual risk of major transfusion-transmitted

viruses in allogeneic US donations
Incidence Infectious Residual risk per
Study Agent (rate per 105 PY) window period donated unit
period (days)
2007-2008 HIV 3.1 9.1 1:1,467,000
2007-2008 HCV 5.1 7.4 1:1,149,000
2006-2008 HBV 3.4 38-30 1:357,000 to 1:280,000¥

¥ Range combines two estimates for the HBsAg-negative window period (38 days vs. 30
days) with two methods for deriving incidence
PY person-years of observation

Epstein JS & Holmberg JA. Transfusion 2010; 50, 1408

SCREENING OF HBV AND HCV
 WHO Recommendation on Screening
(risk-based)

 It is recommended that HCV serology testing be offered to

individuals who are part of a population with high HCV
seroprevalence, or who have a history of HCV risk
exposure/behaviour.

 It is suggested that nucleic acid testing for the detection of

HCV RNA be performed directly, following a positive HCV
serological test to establish the diagnosis of chronic HCV
infection, in addition to nucleic acid testing for HCV RNA as
part of the assessment for starting treatment for HCV
infection.

WHO Guidelines , April 2014

 Risk-based screening of HBV
Populations recommended or required for routine testing of hepatitis B virus infection
Persons born in regions of high and intermediate HBV endemicity (HBsAg prevalence ≥
2%)
US-born persons not vaccinated as infants whose parents were born in regions with HBV
endemicity ≥ 8%
Injection drug users
Men who have sex with men
Injection-drug users
Persons needing immunosuppresive therapy
Persons with elevated ALT/AST of unknown etiology
Donors of blood, plasma, organs, tissues or semen
Hemodialysis patients
All pregnant women
Infants born to HBsAg positive mothers
Household, needle-sharing or sex contacts of persons known to be HBsAg positive
Persons who are the sources of blood or body fluids for exposures that might require
postexposure prophylaxis (e.g. needlestick, sexual assault)
Weinbaum CM. Hepatology, 2009;49:S35
HIV- positive persons
 AASLD Recommendation for HCV Testing (1)
One-time HCV testing is recommended for persons born between 1945 and 1965*, without
prior ascertainment of risk (birth-cohort screening)
Other persons should be screened for risk factors for HCV infection, and 1-time testing
should be performed for all persons with behaviors, exposures and conditions associated
with an increased risk of HCV infection (risk-based screening)
Risk exposures: • Long-term hemodialysis (ever)
• Getting a tattoo in an unregulated setting
• Healthcare, emergency medical and public safety workers after
needlesticks, sharps or mucosal exposures to HCV-infected blood
• Children born to HCV-infected women
• Prior recipients of transfusions or organ transplants, including persons
who 1) were notified that they received blood from a
donor who later tested positive for HCV infection, 2) received a
transfusion of blood or blood components or underwent an organ
transplant before July 1992, 3) Received clotting factor
concentrates produced before 1987
• Persons who were ever incarcerated
*Regardless of country of birth
 AASLD Recommendation for HCV Testing (2)

Risk behaviors: • Injection-drug use (current or ever, including those who inject once)

• Intranasal illicit drug use

Other: • HIV infection

• Unexplained chronic liver disease and chronic hepatitis, including

elevated alanine aminotransferase levels

• Solid organ donors (deceased and living)

 Types of screening programmes

 Integrated: Screening programmes that are integrated

within already existing health care facilities (STD clinics,
HIV/STD service providers, sexual and reproductive health
clinics, emergency departments, community centers,
prisons, health clinics, public laboratories, occupational
physicians etc).

 Non-integrated: Screening programmes that are exclusively

set up for screening (community health clinics, private
practice offices, outreach community screening, city
programmes, schools etc).

Hatzakis A, 2015
 French Guidelines for HBV and HCV (1)
 HBV
• People born or who have lived in countries with an HBV endemic level either high (sub-
Saharan Africa, Asia) or medium (DOM-TOM, Eastern and Southern Europe, North
Africa, middle East, Indian Subcontinent and South America)
• The household and sexual partners of HBV- carrier subjects
• Users of intravenous or intranasal drug
• Patients who may have received massive or iterative blood transfusions
• Travelers in a country with high or medium HBV endemicity
• Adults and children attending psychiatric institutions
• Persons with tattoos or body piercing
• Prisoners and previously incarcerated persons
• People who have sex with different partners
• People with occupational exposure
• Persons with positive serology for HIV or HCV, or having a current or recent sexually
transmitted infection

Bottero J et al, 2016

 French Guidelines for HBV and HCV (2)
 HCV
• Persons who have received blood products or tissue transplant, cells or organs,
before 1992
• persons who injected drugs at least once in their lives
• Persons expose to nosocomial invasive procedures before 1997
• Patients undergoing haemodialysis
• Children born to HCV- positive mother
• Person with positive serology for HIV
• Sexual partners and members of the household of subjects infected with HCV
• Prisoners and previously incarcerated persons
• People from or who received care in countries with a high HCV endemicity
(Southeast Asia, Middle East, Africa, south America)
• Persons who have had tattoos, body piercing, acupuncture or mesotherapy
procedures without the use of disposable or personal equipment
• Persons with elevated ALT blood levels of unknown aetiology

Bottero J et al, 2016

 French Guidelines for HBV and HCV (3)

1. Combine the testing for the chronic viruses (namely, HBV, HCV and
HIV)

2. Continue targeted screening strategy for hepatitis B and C, according

to the risk exposure

3. Set up a population-based testing for HBV, HCV and HIV by offering a

screening test of the following populations at least once in their life:
(1) men aged 18-59 years and (2) pregnant woman at the first prenatal
vistit

4. Encourage the use of rapid POC tests for screening populations who
do not attend traditional medical facilities
Bottero J et al, 2016
 Comparative HBV and HCV screening policies in the non-EU Mediterranean countries - Part A

Algeria Egypt Israel Jordan Lebanon Libya Morocco Tunisia

Antenatal screening HBV HBV HBV
Blood and organ donors Both Both Both Both Both Both Both Both
Blood transfusion or products prior Both Both
to 1992 in EU, or any transfusion
outside EU
Clinical signs or laboratory signs Both Both HCV Both Both Both Both
(including cirrhosis and HCC)
Candidates for chemotherapy or HBV HBV HBV Both
immunosuppressive treatment
Haemophiliacs who received Both Both
concentration factors prior to 1987
Haemodialysis Both Both Both Both Both Both HBV Both
History of shared injecting Both Both Both Both Both Both
equipment
History of long-term imprisonment Both
Hospital surgery patients Both
Household contacts Both Both Both Both
HIV Both Both
IVF candidates Both Both
Men who have sex with men
Migrants from high prevalence Both
countries
Military recruits Both Both Both Both Both

A Hatzakis et al. JVH 2013

 Comparative HBV and HCV screening policies in the non-EU Mediterranean countries - Part B

Algeria Egypt Israel Jordan Lebanon Libya Morocco Tunisia

Organ or tissue transplants prior to Both Both
1992 in EU or outside EU

Pre-employment Both HCV, health Both

care

Pregnant women and newborns Selective risk HBV HBV HBV HBV
groups: HBV

Prenuptial Both HBV HBV

STI clinic patients Both HBV Both HCV

Traditional medicine exposure HBV

Unvaccinated health care workers Both HBV Both HBV

Occupational exposure and /or Both Both Both Both Both HBV HBV
carrying out exposure-prone
procedures

A Hatzakis et al. JVH 2013

 Comparative HBV and HCV screening policies in the non-EU Balkan countries
Bosnia-Herzegovina Croatia Kosovo Serbia
Antenatal screening HBV HBV HBV
Blood and organ donors Both Both Both Both
Blood transfusion or products prior to HCV Both
1992 in EU, or any transfusion outside EU
Clinical signs or laboratory signs (including Both Both Both
cirrhosis and HCC)
Candidates for chemotherapy or Both
immunosuppressive treatment
Haemophiliacs who received Both HCV
concentration factors prior to 1987
Haemodialysis Both Both Both
History of shared injecting equipment Both Both Both
History of long-term imprisonment Both Both
Household contacts Both Both HBV
HIV Both Both
IVF candidates Both
Military recruits HBV
Organ or tissue transplants prior to 1992 Both
in EU or outside EU
Pregnant women and newborns HBV HBV Both
Traditional medicine exposure HBV
Unvaccinated health care workers Both
Occupational exposure and /or carrying Both Both Recommended as a part Both
out exposure-prone procedures of postexposure procedures

A Hatzakis et al. JVH 2013

Considerations for the implementation of successful
screening programmes for HBV and HCV (1)

 Develop clear public awareness campaigns targeted at the general

public and at risk groups.
 Need a clear clinical strategy to deal with HBV and HCV infected
persons.
 Revise clinical guidelines to endorse HBV and HCV screening in
specified risk groups and reinforce dissemination of best practices
for case finding.
 Integrate screening into existing public health and care practices
whenever possible.

Hatzakis A et al. JVH 2011; 18, S1

 Considerations for the implementation of successful
screening programmes for HBV and HCV (2)

 Conduct HBV and HCV screening in HIV/STD clinics, prisons, drug user
services as well as in primary care clinics.
 Simplify screening criteria, e.g adopt age-based criteria for HCV, birth
place for HBV with the aim of providing clear guidance to GPs and those
screening patients.
 Educate providers about the needs for screening and about the
management pathways for HBV- and HCV- infected individuals.
 Always carry out screening in an evidence-based way that defines when
and how often screening should be offered and respects the human rights
of those screened.

Hatzakis A et al. JVH 2011; 18, S1

Considerations for the implementation of successful
screening programmes for HBV and HCV (3)

 Always accompany screening with appropriate counseling of the

individual and his or her family.
 In the case of marginalized or stigmatized groups such as migrants
or IDUs, one must ensure that individuals are not stigmatized
because of their group membership or their viral hepatitis status.

Hatzakis A et al. JVH 2011; 18, S1

Key factors necessary for the successful implementation of
prevention and management programmes targeting HBV
and/or HCV (1)

 Reliable local epidemiological data to communicate with policymakers.

 Clinical leadership from specialist centres as well as from public health,
social services and other relevant professional groups.
 Motivation of all those involved in programme using quantifiable goals
(e.g. 75% of patients with HepC will be aware of their infection by a given
year).
 Inclusion of concrete goals to extend treatment in line with existing –and
desired- treatment capacity.

Hatzakis A et al. JVH 2011; 18, S1

Key factors necessary for the successful implementation of
prevention and management programmes targeting HBV
and/or HCV (2)

 Recognition of the need and potential of therapeutic developments to

confer true patient benefits.
 Strong, continuous patient advocacy.
 Close and ongoing dialogue between patients, clinical leads, public health
specialists and policymakers.
 Awareness campaigns to increase testing through GPs and other primary
care providers.
 Systematic referral system for individuals screening positive to secondary
care.

Hatzakis A et al. JVH 2011; 18, S1

Key factors necessary for the successful implementation of
prevention and management programmes targeting HBV
and/or HCV (3)

 Targeted awareness campaigns (e.g. aimed at different immigrant

communities).
 Strengthening of network between hospitals, GPs and physicians
in special settings (e.g. prisons or sexual health clinics).
 Shared patient management between specialists and GPs to lessen
the burden on hospitals.

Hatzakis A et al. JVH 2011; 18, S1

 Cost-effectiveness analysis of birth-cohort screening
in the US

 HCV infected (birth-cohort 1945-1965): 69% of the total HCV infected

 HCV prevalence (birth-cohort 1945-1965): 3.6%
 Scenarios:
a) No screening or treatment.
b) Risk-based screening of individuals unaware of HCV (1% per year for 20 years) and
offer of peg-IFN+R.
c) One time HCV birth-cohort (1945-1965) screening of individuals unaware of HCV and
peg-IFN+R treatment.
d) One time HCV birth-cohort (1945-1965) screening of individuals unaware of HCV and
1) peg-IFN+R in patients with HCV-2 or 3 and, 2) peg-IFN+R+direct-acting antiviral in
patients with genotype 1.
 Screening cost per case identified: 2.874 USD
 Incremental cost-effectiveness ratio (ICER):
 B: 15,700 USD/QALYS
 C: 15,700 USD/QALYS
 D: 73,700 USD/QALYS

Rein DB et al. Ann Intern Med, 4 Nov. 2011

 Priorities among effective clinical preventive services
(National Committee on Prevention Priorities)
Services CPB CE Total
Aspirin chemoprophylaxis 5 5 10
Childhood immunization series 5 5 10
Tobacco-use screening and brief intervention 5 5 10
Colorectal cancer screening 4 4 8
Hypertension screening 5 3 8
HCV birth
Influenza immunization of adults 50yrs or older 4 4 8 cohort
(1945-
Pneumococcal immunization of adults 65yrs or older 3 5 8 1965)
screening
Problem drinking screening and brief counseling 4 4 8

Maciosek MV et al. Am J Prev Med 2006; 31, 1

Vision screening of adults 65yrs or older 3 5 8
Cervical cancer screening 4 3 7
Cholesterol screening 5 2 7
Breast cancer screening 4 2 6

Hatzakis A et al, 2012

Chlamydia screening 2 4 6
Calcium chemoprophylaxis 3 3 6
Vision screening-children 2 4 6
CPB: Clinically Preventable Burden, CE: Cost-Effectiveness
 Cost of screening per case identified in the US
Disease Conditions Cost per case (USD)
Chronic HBV Prevalence of HBsAg: 2% 750-3,752
Chronic HCV Prevalence of anti-HCV: 3.6% 2,874
(birth-cohort 1945-1965)
HIV/AIDS Prevalence of anti-HIV: 1% 2,133 (1,733-3,733)
Diabetes mellitus Two-step glucose 4,064
Hearing disorders in Universal newborn screening 16,000
newborns
Metabolic disorders in Universal mass spectometry 68,000
newborns screening
Down syndrome 1st and 2nd trimester evaluation 690,000

Weinbaun CM et al. Hepatology, 2011;49: S35.

Hutton DW et al. Ann Intern Med, 2007;147:460.
Rein DB et al. Ann Intern Med, 2011: Nov 4