1. Hepatitis B Virus Dr R V S N Sarma., M.D., [SLIDE 1] Title Slide
This slide set presents an overview of the clinical and epidemiologic features for viral hepatitis A, B, C, D, and E and prevention measures for these infections. More detailed information regarding the epidemiologic features and prevention measures can be found on-line at for hepatitis A read the MMWR, Prevention of Hepatitis A Through Active or Passive Immunization: Recommendations of the Advisory Committee on Immunization Practices, Vol. 48, No RR12;1, 10/01/1999; for hepatitis B read the MMWR, Recommendations to Prevent Hepatitis B Virus Transmission – US, Vol.44, No 30;574, 08/04/1995, Updated; for hepatitis C read the MMWR, Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCV-Related Chronic Disease, Vol. 47, No RR19;1, 10/16/1998.
Dr R V S N Sarma., M.D.,

2. Geographic Distribution of Chronic HBV Infection
[SLIDE 41, SLIDE 42] Global Patterns of Chronic HBV Infection, Geographic Distribution of Chronic HBV infection*
Approximately 45% of the global population live in areas with a high prevalence of chronic HBV infection (> 8% of the population is HBsAg‑positive); 43% in areas with a moderate prevalence (2%‑7% of the population is HBsAg‑positive); and 12% in areas with a low prevalence (< 2% of the population is HBsAg‑positive). In high prevalence areas, the lifetime risk of HBV infection is >60%, and most infections are acquired at birth or during early childhood when the risk of developing chronic infection is greatest. In these areas, because most infections in children are asymptomatic, very little acute disease related to HBV occurs, but rates of chronic liver disease and liver cancer in adults are very high. In moderate prevalence areas, the lifetime risk of being infected is 20%‑60% and infections occur in all age groups. Acute disease related to HBV is common in these areas because many infections occur in adolescents and adults; however, the high rates of chronic infection are maintained mostly by infections occurring in infants and children. In low prevalence areas, the lifetime risk of infection is <20%. Most HBV infections in these areas occur in adults in relatively well defined risk groups.
*(Note: The map of HBsAg prevalence generalizes available data and patterns may vary within countries.)
HBsAg Prevalence
³8% - High
2-7% - Intermediate
<2% - Low

3. Global Patterns of Chronic HBV Infection
High (>8%): 45% of global population
lifetime risk of infection >60%
early childhood infections common
Intermediate (2%-7%): 43% of global population
lifetime risk of infection 20%-60%
infections occur in all age groups
Low (<2%): 12% of global population
lifetime risk of infection <20%
most infections occur in adult risk groups
[SLIDE 41, SLIDE 42] Global Patterns of Chronic HBV Infection, Geographic Distribution of Chronic HBV infection*
Approximately 45% of the global population live in areas with a high prevalence of chronic HBV infection (> 8% of the population is HBsAg‑positive); 43% in areas with a moderate prevalence (2%‑7% of the population is HBsAg‑positive); and 12% in areas with a low prevalence (< 2% of the population is HBsAg‑positive). In high prevalence areas, the lifetime risk of HBV infection is >60%, and most infections are acquired at birth or during early childhood when the risk of developing chronic infection is greatest. In these areas, because most infections in children are asymptomatic, very little acute disease related to HBV occurs, but rates of chronic liver disease and liver cancer in adults are very high. In moderate prevalence areas, the lifetime risk of being infected is 20%‑60% and infections occur in all age groups. Acute disease related to HBV is common in these areas because many infections occur in adolescents and adults; however, the high rates of chronic infection are maintained mostly by infections occurring in infants and children. In low prevalence areas, the lifetime risk of infection is <20%. Most HBV infections in these areas occur in adults in relatively well defined risk groups.
*(Note: The map of HBsAg prevalence generalizes available data and patterns may vary within countries.)

4. Hepatitis B by Year, United States, 1966 - 2000
HBsAg screening of pregnant women
recommended
Infant Immunization
recommended
Vaccine
licensed
OSHA Rule enacted
Adolescent Immunization recommended
[SLIDE 15] Hepatitis B by year, United States, 1966 – 2000
Since hepatitis B vaccine was licensed for use in the United States in 1981, the incidence of acute hepatitis B has changed dramatically. During the 1980s, use of hepatitis B vaccine had little impact on disease incidence, which actually increased during the early 1980s. The incidence declined between 1985 and 1988, and between 1988 and 1991, when fewer cases were reported among men who have sex with men and among injecting drug users, respectively. In both of these groups the decline in incidence was likely related to behavioral changes in response to the epidemic of acquired immunodeficiency syndrome (AIDS) rather than to vaccine use. The incidence has continued to decline during the first half of the 1990s; a likely contributing factor for this most recent decline is the widespread use of hepatitis B vaccine in response to regulations issued by the Occupational Safety and Health Administration. Future declines in incidence are expected to occur as a result of the implementation of routine infant and routine adolescent vaccination, which have been recommended in the 1990s.
Decline among
injecting
drug users
Decline among MSM & HCWs
Source: NNDSS

5. Hepatitis B – Clinical Features
Incubation period Average days
Range days
Clinical illness <5 yrs, <10% (jaundice) >5 yrs, 30%-50%
Acute case-fatality rate %-1%
Chronic infection <5 yrs, 30%-90% >5 yrs, 2%-10%
Premature mortality from chronic liver disease %-25% 29

6. Natural History of Hepatitis B
Infection
Asymptomatic
Resolved
Immune
Chronic infection
Cirrhosis
Liver cancer
Symptomatic
acute hepatitis B
Chronic
infection

7. Serological Markers of HBV
HBsAg
Screening test
Anti HBsAb
Vaccinated or Infected.
Anti HBcAb
Remote past Infection
HBeAg
Active Multiplication
Viral DNA
Quantitative evidence
AST/ALT
Acute Liver Injury
Serological Markers of HBV

8. HEPATITIS B TESTING HBsAg HBeAg HBeAb Viral DNA AST/ALT Neg Positive
Normal
> 2 fold
HBeAb
Negative
Viral DNA
<105 copies
> 105 copies

9. Hepatitis Clinical Stages
Chronic Active Hepatitis B
HbsAg +ve for > 6 months
Serum HBV DNA > 105 copies
Persistent ↑ AST /ALT
Necro inflammatory score 4
Inactive Carrier of B
HBsAg + for > 6 months
HBeAg - and anti HBeAb +
Serum HBV DNA < 105 copies
Persistent normal AST /ALT
Resolved Hepatitis B
Presence of antiHBc and anti HBs
HBsAg- and undetectable HBV DNA load
Normal AST and ALT

10. Chronic Hepatitis B HBeAg Positve HBeAg Negative HBeAg Seroconversion
HBeAg Clearnace
HBeAg Reversion
HBsAg carrier state

11. Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Weeks after Exposure
Symptoms
HBeAg
anti-HBe
Total anti-HBc
IgM anti-HBc
anti-HBs
HBsAg 4 8 12 16 20 24 28 32 36 52
100
Titer
[SLIDE 34] Acute Hepatitis B Virus Infection with Recovery: Typical Serologic Course
Serologic markers of HBV infection vary depending on whether the infection is acute or chronic.
The first serologic marker to appear following acute infection is HBsAg, which can be detected as early as 1 or 2 weeks and as late as 11 or 12 weeks (mode, 30‑60 days) after exposure to HBV. In persons who recover, HBsAg is no longer detectable in serum after an average period of about 3 months. HBeAg is generally detectable in patients with acute infection; the presence of HBeAg in serum correlates with higher titers of HBV and greater infectivity. A diagnosis of acute HBV infection can be made on the basis of the detection of IgM class antibody to hepatitis B core antigen (IgM anti‑HBc) in serum; IgM anti‑HBc is generally detectable at the time of clinical onset and declines to subdetectable levels within 6 months. IgG anti‑HBc persists indefinitely as a marker of past infection. Anti‑HBs becomes detectable during convalescence after the disappearance of HBsAg in patients who do not progress to chronic infection. The presence of anti‑HBs following acute infection generally indicates recovery and immunity from reinfection.

12. Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course
IgM anti-HBc
Total anti-HBc
HBsAg
Acute
(6 months)
HBeAg
Chronic
(Years)
anti-HBe 4 8 12 16 20 24 28 32 36 52
Weeks after Exposure
Titer
[SLIDE 35] Progression to Chronic Hepatitis B Virus Infection: Typical Serologic Course
In patients with chronic HBV infection, both HBsAg and IgG anti‑HBc remain persistently detectable, generally for life. HBeAg is variably present in these patients. The presence of HBsAg for 6 months or more is generally indicative of chronic infection. In addition, a negative test for IgM anti‑HBc together with a positive test for HBsAg in a single serum specimen usually indicates that an individual has chronic HBV infection.

13. HBV Modes of Transmission
Sexual
Parenteral
Perinatal 2 2 2

14. Low / not High Moderate Detectable Concentration of HBV
in Various Body Fluids
Low / not
High
Moderate
Detectable
Semen
Serum
Vaginal fluid
Blood
Wound exudates
Saliva
Urine
Feces
Sweat
Tears
Breast milk 1 1 1

15. Risk Factors Associated with
Reported Hepatitis B,
[Slide 8] Risk Factors Associated with Reported Hepatitis B, , United States
Of persons with acute hepatitis B reported in the National Notifiable Diseases Surveillance System and the Viral Hepatitis Surveillance Program from 1990‑2000, 36% had a sexual risk factor (>1 sex partner during the previous 6 months, sex contact with a person with hepatitis, or men who have sex with men), 14% reported injecting drug use, and 18% had other risk factors (e.g., household contact with a hepatitis patient, health care employment). No risk factor could be identified for 32% of reported cases.
*Other: Surgery, dental surgery, acupuncture, tattoo, other percutaneous injury
Source: NNDSS/VHSP

16. Elimination of HBV Transmission
Strategy
Prevent perinatal HBV transmission
Routine vaccination of all infants
Vaccination of children in high-risk groups
Vaccination of adolescents
all children up through age 18
Vaccination of adults in high-risk groups
[SLIDE 47] Elimination of Hepatitis B Virus Transmission, United States: Strategy
The hepatitis B elimination strategy includes the following components: 1) preventing perinatal HBV transmission by screening all pregnant women for hepatitis B surface antigen (HBsAg) and providing hepatitis B immune globulin (HBIG) and hepatitis B vaccine to infants of HBsAg‑positive mothers; 2) providing hepatitis B vaccine to all infants as part of the routine childhood vaccination schedule; 3) making special efforts to provide catch‑up vaccination for children in high risk groups, including Alaska Natives, Pacific Islanders and infants of immigrants from countries with a high prevalence of chronic HBV infection; 4) providing hepatitis B vaccine to adolescents, including a) all previously unvaccinated children at 11‑12 years of age and b) adolescents of all ages who are at high risk for infection (see adult high‑risk groups below); and 5) vaccinating adults in high‑risk groups including a) men and women with a history of other sexually transmitted diseases and persons who have a history of multiple sex partners (>1 partner/6 months), b) household contacts and sex partners of persons with chronic HBV infection and health care and public safety workers who have exposure to blood in the workplace, d) clients and staff of institutions for the developmentally disabled, e) international travelers who plan to spend >6 months in countries with high rates of HBV infection and who will have close contact with the local population, f) injecting drug users, g) sexually active homosexual and bisexual men, and h) recipients of clotting‑factor concentrates.

17. Hepatitis B Vaccine Licensed in 1982; currently recombinant
3 dose series, typical schedule 0, 1-2, 4-6 months - no maximum time between doses (no need to repeat missed doses or restart)
2 dose series (adult dose) licensed by FDA for year olds (Merck)
Protection ~30-50% dose 1; 75% - 2; 96% - 3; lower in older, immunosuppressive illnesses (e.g., HIV, chronic liver diseases, diabetes), obese, smokers
Vaccine advisory groups that have endorsed this strategy include the Immunization Practices Advisory Committee to the U.S. Public Health Service (ACIP), the American Academy of Pediatrics (AAP), the American Academy of Family Physicians (AAFP), and the American College of Physicians (ACP).

18. Hepatitis B Vaccine Safety
Administered to over 12 million infants and children in the United States
– side effects rare
Anaphylaxis estimated to occur in 1/600,000 doses given
No scientific data to link hepatitis B vaccine with multiple sclerosis (MS), other autoimmune diseases, autism
Vaccine advisory groups that have endorsed this strategy include the Immunization Practices Advisory Committee to the U.S. Public Health Service (ACIP), the American Academy of Pediatrics (AAP), the American Academy of Family Physicians (AAFP), and the American College of Physicians (ACP).

19. Hepatitis B Vaccination ACIP Recommendations
Routine infant
Ages “catch up”, and through age 18(VFC eligible)
Over 18 – high risk
Occupational risk (HCWs)
Hemodyalisis patients
All STD clinic clients
Multiple sex partners or prior STD
Inmates in Correctional settings
MSM
IDU
Institution for developmental disability
Pre-vaccination testing – if cost effective
Post-vaccination testing – 1-2 months after last
shot, if establishing response critical (HCW)