Hepatitis B Disease

Surveillance and Health

Statistics SALWA F RASHID MD, CPH

OCTOBER 2015

Hepatitis B

An infection of the liver caused by HBV

The hepatitis B virus was discovered in 1965 by Dr Baruch Blumberg

Hepadnaviridae family

Small, partially double stranded DNA Virus

Numerous antigenic components

Humans are only known host

May retain infectivity for more than 7 days at room temperature

Blood banks began using the test in 1971 to screen blood donations, risk of hepatitis B infections from a

blood transfusion decreased by 25 percent

Hepatitis B

About 2 billion persons around the world have

been infected with HBV

About 250 million have chronic infections around

the globe

Significant cause of morbidity and mortality

780 000 estimated deaths/year due to

complications. (1)

Hepatitis B

90% of infected adults will recover during the first year of infection

5% of adults will develop chronic hepatitis B infection.

30-50 % of adults with chronic hepatitis B will develop cirrhosis or HCC

Children under 6 years old are at risk of developing chronic hepatitis B when infected with the virus

Hepatitis B

In 2013, 3,050 cases of acute hepatitis B in the United States were reported to the CDC

incidence of reported acute hepatitis B was 1.0 cases per 100,000 population

actual number of new infections is estimated to be approximately tenfold higher.

In Kentucky 2013, 214 cases of acute Hepatitis B infection was reported. With rate of 4.9/100,000 population (2)

Hepatitis B

700,000–1.4 million individuals were estimated to

have chronic hepatitis B in the United States (2)

http://www.cdc.gov/hepatitis/statistics/2013survei

llance/index.htm - tabs-801937-1

Hepatitis B Prevalence/GloballyRegion/Country Source Prevalence Most common age Most common mode of

transmission

Increasing prevalence from north to Southeast Asia, China, Pacific island, sub-Saharan Africa, Alaska

WHO 8% or > Perinatal and earlychildhood

Vertical (mother to child during

birth), horizontal in early

childhood Percutaneous

Mediterranean basin, eastern Europe, central Asia, Japan, Latin and South America, Middle East

WHO 2-7 % Early childhood Percutaneous, sexual

United States and Canada, western Europe, Australia, New Zealand

WHO ≤1 % Adult Sexual, percutaneous

INCIDENCE OF HEPATITIS B

Area Source Year Incidence of acute Hepatitis

B/100,000 population

Rate of chronic

Hepatitis B /100,1000

population

Mortality

#

Mortality

Rate

Globally WHO (3) 780 000

United States CDC (2) 2013 1.0 7.7 1,873 0.52

Kentucky CDC (2) 2013 4.9

Canada Study 1 1998/1999 2.3

Europe Studty 2 2000 1.33(M)

0. 58(F)

Taiwan Study 3 1984

2004

9.8

0.6

Italy StuS 19912010

5.1

0.9

Epidemiology of Hepatitis B and

vaccine effectGeographical area/country Source Year Prevalence Incidence Acute Hep B Mortality # Mortality

Rate

United States CDC

1990 (4)20042013

8.52.11.0

1,873

0.52

Kentucky CDC 2013 0.4

U.S and Canada WHO 2015 <1%

CanadaCanada overallCanada BornInuit population

Immigrants from highly endemic

countries(2)

Study 4 1998/1999

2001 0.5-1%

0.1%

6.9%

7.4%

2.3

Epidemiology of Hepatitis B and

vaccine effectGeographical area/country Source Year Prevalence Incidence Acute Hep B

Europe

Northern Europe (Scandinavian

countries and the United Kingdom

Southern Europe

Study #4

< 0.1%

> 8%

1.33(M) 0. 58 (F)

IranStuStudy

2005 2.6%

Africa

(Gambia & Senegal),

Nigeria

15%

13.6%

14.1%(in

pregnant

women)

Epidemiology of Hepatitis B

and effect of vaccinationEastern Mediterraneancountries of North Africa through the MiddleEast to Pakistan

(Study 5) Egypt

1985

Egypt

2009 and 2010

11.7% (Incidence)

4.2%

(Decreased after immunization)

Incidence

South-East Asia

Bangladesh, Bhutan,North Korea, India,Indonesia, MaldivesMyanmar, Nepal, Sri Lanka,Thailand and Timor-Leste.

Study (4)

2005

India

Thailand1992

Thailand

2004

>5%

2-8%

7. 2

4%(universal vaccine)

IncidenceWestern Pacific

Australia, Brunei Darussalam,

Cambodia, China, Cook Islands, Fiji,

Japan, Kiribati, Lao People’s

Democratic Republic, Malaysia,

Marshall Islands, Nauru, New Zealand,

Niue, Papua New Guinea, Philippines,

Republic of Korea, Samoa, Singapore,

Solomon Islands, Tonga, Tuvalu,

Vanuatu, and Vietnam.

Study#4non-Aboriginal populations of

Australia and New Zealand

The Northern and Central Asian

small South Pacific island nations

China 1992

2002(small surcharge)

2005 (no charge)

2009

0.1%

7 and 12

30

9.8(parents had to

pay for vaccines)

7.2(children <1%)

Refugees resettled in Kentucky

Refugees resettled in Kentucky

October 2012-2015 Refugees who went to a

clinic in Jefferson County

October 2012-2015 Refugees who went to

a clinic in Jefferson County

Methods of transmission

The virus is blood born transmitted by:

Exposure to infectious blood or body fluids

Vertical transmission during birth

Injected drug use

Sexual contact

Blood transfusion

Dialysis

Tattooing

Acupuncture

Health care workers

House hold contact with skin or mucosal abrasion who come in contact with infectious fluid

Diagnosis

Signs and symptoms

Acute infection

(Acute viral Hepatitis)

Malaise, Nausea and vomiting, fever, general aches, abdominal pain, dark

color urine, and

Either a) Jaundice or b) Elevated ALT>100 IU/L

• Laboratory Criteria

- HBsAg positive Immunoglobulin M (IgM)

- antibody to hepatitis B core antigen (IgM anti-HBc) positive (if done

- patient not known to have chronic hepatitis B

Hepatitis B

Symptoms last for few weeks and then the infection clears leaving

the person with natural immunity (due to infection) A few people may

have more severe liver disease

Diagnosis

• The likelihood of developing symptoms of acute

hepatitis is age dependent:

90% of infected adults will recover during the

first year of infection

Diagnosis

(fulminant hepatic failure)

sever form and may result in death

develops in 1% of cases *

(Asymptomatic infection)

May go unrecognized

Diagnosis

Chronic infection

presence of HBsAg in serum for at least 6 months or the presence of

HBsAg and the absence of anti-HBc immunoglobulin M (IgM). *

(asymptomatic)

(chronic hepatitis), persons with chronic hepatitis can be a source of

spreading the infection

chronic inflammation of the liver can lead to cirrhosis which in turn

leads to liver cancer (Hepatocellular carcinoma)

Alcohol use should be avoided in patients with chronic hepatitis B

infection as it will increase there risk for both ( Liver cirrhosis and

caner)(14) hepatocellular carcinomas.

Diagnosis

The risk of developing chronic infection is

inversely associated with age

>90% of infants infected at birth or in their first

year of life

25% to 50% of children ages 1 to 5 years

5% to 10% of older children and adults

Diagnosis

Laboratory tests:

LFT: increased ALT, AST (transaminitis)

Serum Assays:

HBsAg: marker of infection

HBsAb: marker of immunity or recovery

Diagnosis/Laboratory tests

Anti-HBc-IgM: marker for acute infection

Anti-HBc-IgG: marker for chronic infection

HBeAg: active replication

Anti-Hbe: inactive replication

Diagnosis/Laboratory tests

HBV-DNA: active replication (more accurate),

detected by PCR test, (viral load), to determine

infection status and to follow up response for

treatment.

Hepatitis B

Early during the infection the HBs-Ag can be undetectable (Window*)

and the only think that appears is anti-HBc IgM

after HBsAg appears, HBeAg will appear which is associated with

high replication rates and increased infectivity

When HBe-Ag is cleared, and anti-HBe levels increase, there will a

fast decrease in viral replication

Window period is the time between clearance of Hbs-Ag and the

appearance of anti-HBs and anti-HBc IgG

Persons who are able to clear the infection will have undetectable

HBsAg, and positive IgG to HBs-Ag and HBc-Ag.

Hepatitis B

Persons in whom HBsAg stay reactive for six months or more are

known as hepatitis B carriers

They can have chronic hepatitis which is shown by elevated liver

enzymes most commonly (ALT) due to inflammation of the liver

which occurs in the immune clearance phase of the chronic infection.

Carriers with HBeAg negative, especially persons who are infected

during adulthood have minimal replication and therefore they are at

lower risk of developing liver cirrhosis and cancer or infecting others

Prevention The hepatitis B vaccine is the mainstay of hepatitis B prevention.

Vaccine is given within 24 hours of birth.

Immunologic memory develops following vaccination

Antibody level declines following successful vaccination

Anamnestic response upon exposure (antibody level increases quickly)

excellent record of safety and effectiveness

first hepatitis B vaccine, was initially a heat-treated form of the virus.

In 1981, the FDA approved a more sophisticated plasma-derived hepatitis B vaccine for human use. This “inactivated” type of vaccine

The use of this vaccine was discontinued in 1990 and it is no longer available in the U.S.

Current Recombinant Hepatitis B Vaccines

In 1986, research resulted in a second generation of genetically engineered (or DNA recombinant) hepatitis B vaccines.

Prevention

Since 1982, over 1 billion doses of hepatitis B vaccine

have been given globally.

Vaccination decreased the rate of chronic infection to

less than 1% in countries known to have increased rates

prior to the vaccine (8-15%)

As of 2013, 183 Member States vaccinate infants against

hepatitis B as part of their vaccination schedules and 81%

of children received the hepatitis B vaccine

Prevention

IMPACT OF PREVENTION OF TRANSMISSION

Prevention strategies

Primary prevention of new infections (vaccines and post-exposure

prophylaxis)

Secondary prevention of HBV transmission by appropriate sexual and

sanitary practices.

Tertiary prevention of the pathological consequences of chronic HBV by

anti-viral treatment.

The risk of progression from acute to chronic infection is inversely

proportional to the age of infection.

90% of infants who acquire HBV infection from their mothers at birth

become chronically infected, whereas in adults

5% of acute HBV cases remain chronically infected

Who should get the vaccine?

Everyone 18 years of age and younger

Adults over 18 who are at risk

Who should get the vaccine?

Household contacts of persons with chronic HBV infection

Sex contacts of infected people

Persons with multiple sexual partners

Homosexual men

Injected drugs users

Health care workers who might be exposed to blood or body

fluids

Patients on Hemodialysis

Persons who need 3 doses

Infant whose mother is infected with HBV:

First Dose: within 12 hours of birth

Second Dose: 1 - 2 months of age

Third Dose: 6 months of age

Persons who need 3 doses

Infant whose mother is NOT infected with HBV:

First Dose: between birth – 2 months of age

Second Dose: 1 - 4 months of age (at least 1 month

after first dose)

Third Dose: 6 - 18 months of age (at least 2 months

after the second dose)

Hepatitis B Vaccine/Adult Schedule

Usual Minimum

Dose Interval Interval

Dose 1

Dose 2 1 month 4 weeks

Dose 3 4-6 months 8 weeks*

*third dose must be separated from first dose by at least 16 weeks

Treatment

Key recommendations:

Identifying who needs the treatment by non-invasive test

to know the stage of the liver disease.the use of a few

simple non-invasive tests to assess the stage of liver

disease

prioritizing treatment for those with cirrhosis

Use tenofovir or entecavir, for the treatment of chronic

hepatitis B; which are known to be effective and safe

regular monitoring by lab tests for early detection of liver

cancer, and to follow up response to treatment.

Bibliography (1) World Health Organization (WHO). Hepatitis B - Updated July 2015.

http://www.who.int/mediacentre/factsheets/fs204/en/

(2) Surveillance for Viral Hepatitis – United States, 2013 (Centers for Disease Control and Prevention)

http://www.cdc.gov/hepatitis/statistics/2013surveillance/index.htm#tabs-801937-1

3) World Health Organization (WHO). Hepatitis B - Updated July 2015

http://www.who.int/csr/disease/hepatitis/whocdscsrlyo20022/en/index1.html#world

4) Centers for Disease Control and Prevention (CDC). Web.

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5251a3.htm

5) Hepatitis B (WHO)

http://www.who.int/mediacentre/factsheets/fs204/en/

(6)Hollinger FB, Liang TJ. Hepatitis B Virus. In: Knipe DM et al., eds. Fields Virology, 4th ed. Philadelphia, Lippincott Williams & Wilkins, 2001:2971-3036.

(7) Guidotti LG et al. Hepatitis B virus nucleocapsid particles do not cross the hepatocyte nuclear membrane in transgenic mice. Journal of Virology, 1994, 68:5469-5475.

(8) Mahoney FJ. "Update on Diagnosis, Management, and Prevention of Hepatitis B Virus Infection." Clinical Microbiology Reviews 12.2 (1999): 351-66. (9) McMahon BJ, et al. "Acute Hepatitis B Virus Infection: Relation of Age to the Clinical Expression of Disease and Subsequent Development of the Carrier State." The Journal of Infectious Diseases151.4 (1985): 599-603.

(10) Centers for Disease Control and Prevention(CDC). Hepatitis B VIS. Page last updated: June 18, 2013. http://www.cdc.gov/vaccines/hcp/vis/vis-statements/hep-b.html

(11)"Hepatitis B Vaccine History." Hepatitis B Foundation: Vaccine History. Web.

http://www.hepb.org/professionals/hepatitis_b_vaccine.htm

Bibliography

Study 1: Zhang J, Zou S, Giulivi A. Epidemiology of hepatitis B in Canada. The Canadian

Journal of Infectious Diseases. 2001;12(6):345-350. Magdzik, Wiesław. "Hepatitis B

Epidemiology in Study 2: Poland, Central and Eastern Europe and the Newly Independent

States." Vaccine 18 (2000)

Study 3: Romano L., Paladini S., and Zanetti AR. "Twenty Years of Universal Vaccination

against Hepatitis B in Italy: Achievements and Challenges." Journal of Public Health

Research 1.2 (2012): 126-9.

Study 4: Papastergiou, Vasilios, et al. "Global Epidemiology of Hepatitis B Virus (HBV)

Infection." Current Hepatology Reports 14.3 (2015)

Study 5: Shalaby S, Kabbash IA, El Saleet G, et al. Hepatitis B and C viral infection:

prevalence, knowledge, attitude and practice among barbers and clients in Gharbia

governorate, Egypt. East Mediterr Health J. 2010; 16(1):10-17.