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“The only thing necessary for these diseases to the triumph is for good people and governments to do nothing.”


From the Hepatitis C Virus Advocate at:

EASL International Consensus Conference on Hepatitis B

Miriam J. Alter, Division of Viral Hepatitis, Centers for Disease Control
and Prevention, Atlanta, GA, USA


Hepatitis B virus (HBV) infection is a major public health problem and cause
of infectious disease mortality worldwide. Approximately 2 billion people -
one third of the world's population - have serologic evidence of past or
present HBV infection, and 350 million people are chronically infected.
Each year over 1 million people die from HBV-related chronic liver disease,
including cirrhosis and hepatocellular carcinoma (HCC) (1). HCC is one of
the most common cancers worldwide, and HBV is responsible for at least 75%
of these cancers (2).

Geographic Patterns of Transmission
The endemicity of HBV infection varies greatly worldwide (3,4) and is
influenced primarily by the predominant age at which infection occurs (Table
1).  Endemicity of infection is considered high in those parts of the world
where at least 8% of the population is HBsAg-positive.  In these areas, 70%
to 90% of the population generally have serological evidence of previous HBV
infection.  Almost all infections occur during either the perinatal period
or early in childhood which accounts for the high rates of chronic HBV
infection in these populations.  Risk of HBV infection continues after the
first five years of life, but its eventual contribution to the high rate of
chronic infection is less significant.  Chronic infection with HBV is
strongly associated with HCC, and areas with a high endemicity of chronic
HBV infection have the highest death rates from this neoplasm.

In areas of the world with an intermediate pattern of HBV infection, the
prevalence of HBsAg positivity ranges from 1% to 7% and serological evidence
of past infection is found in 10% to 60% of the population.  In these areas
there are mixed patterns of infant, early childhood and adult transmission.

In most developed parts of the world, the prevalence of chronic HBV
infection is <1%, and the overall infection rate is 5% to 7%.  Within these
areas most infections occur among high risk adult populations that include
injection drug users, persons with multiple heterosexual partners, men who
have sex with men (MSM), and health care workers.  Although the proportion
of infant and early childhood infections is low, they can account for a
disproportionately high number of chronic HBV infections.


Modes of Transmission
The incubation period of hepatitis B is long, ranging from 45-160 days
(average 120). HBV is transmitted by percutaneous and mucous membrane
exposures to infectious blood and body fluids that contain blood.  Although
HBsAg has been detected in a wide variety of body fluids, only serum, semen,
and saliva have been demonstrated to be infectious (5,6).  The presence of
HBeAg in serum correlates with higher titers of HBV (up to 109 particles/mL)
and greater infectivity (7-9).  However, HBV strains that have mutations in
the precore region of the viral genome that prevents expression of HBeAg
also have been associated with transmission (10).

 Percutaneous exposures that have resulted in HBV transmission include
transfusion of blood or blood products (11,12), contaminated equipment used
for therapeutic injections and other health-care related procedures (13-17),
illegal injection drug use (18), and needle sticks or other injuries from
sharp instruments sustained by hospital personnel (7,19).  In addition,
occasional outbreaks of hepatitis B have been associated with tattooing and
acupuncture (20,21).  Because HBV is stable on environmental surfaces for >7
days (22), indirect inoculation of HBV can also occur via inanimate objects.

 Perinatal and sexual transmission of HBV usually results from mucous
membrane exposures to infectious blood or serum-derived body fluids (23,24).
No infections have been demonstrated in susceptible persons orally exposed
to HBsAg-positive saliva, although transmission has been demonstrated to
animals by subcutaneous inoculation of saliva (5,6,25,26).

 The risk of perinatal HBV transmission has been well described.  This risk
is greatest for infants born to women who are HBeAg-positive and ranges from
70%-90% at 6 months of age; about 90% of these children remain chronically
infected (24).  The risk of perinatal infection among infants born to
HBeAg-negative mothers ranges from 10%-40%, with 40%-70% of these infected
infants remaining chronically infected (24,27).  Children born to
HBsAg-positive mothers who do not become infected during the perinatal
period remain at high risk of infection during early childhood (28-30); in
one study, 40% of infants born to HBeAg-negative mothers became infected by
5 years of age (27).

Person-to-person spread of HBV can occur in settings involving nonsexual
interpersonal contact over a long period of time, such as among household
contacts of a chronically infected person (31-34).  The precise mechanisms
of transmission are unknown; however, frequent interpersonal contact of
nonintact skin or mucous membranes with blood containing secretions or
perhaps saliva are the most likely modes of transmission (35).  Because of
the extremely high concentration of virus in the blood, the number of
virions in even very small amounts of blood or body fluids can be quite
high.  In addition, HBsAg contamination of surfaces is widespread in homes
of chronically infected persons (35), and HBV remains infectious for long
periods of time under ambient conditions.

Among adults, high-risk sexual activity is one of the most frequent routes
of transmission for HBV.  Historically, MSM were one of the groups at
highest risk for HBV infection. Infection in this risk group has been
associated with receptive anal intercourse, increased numbers of sexual
partners, and number of years of sexual activity (70% of homosexual men were
infected after 5 years of sexual activity) (23).  Similar factors have been
associated with an increased risk of HBV infection among heterosexual men
and women, including number of sexual partners, number of years of sexual
activity, and history of other sexually transmitted diseases (STDs) (23).

Transmission of HBV from persons with acute or chronic hepatitis B to their
sexual partners is also an important source of infection (23). However, most
persons with chronic HBV infection are not aware that they are infected.
These silent carriers are the most likely source of infection for persons
with multiple sexual partners.

 EASL International Consensus Conference on Hepatitis B




Current Epidemiology
In most developed countries, including those in northern and western Europe,
the highest incidence of acute hepatitis B is among young adults, and
high-risk sexual activity and injecting drug use account for most cases of
newly acquired hepatitis B (36-39).  However, even in these low HBV endemic
countries, a substantial number of children become infected with HBV, many
of whom belong to families that have immigrated from high HBV endemic
countries (3,40,41).  Since over 90% of childhood HBV infections are
asymptomatic, the true incidence of childhood disease is not accurately
represented by most surveillance data, which reflect reported cases of
clinically apparent disease.

Although HBV infection was recognized as a frequent occupational hazard
among persons working in laboratories or exposed to blood while caring for
patients (42,43), hepatitis B vaccination of health care workers (and
implementation of universal precautions) has made this infection a rare
event in this population (44). HBV transmission from infected healthcare
personnel to patients is relatively uncommon, but has occurred during
invasive surgical, obstetrical, or dental procedures.  Most of the reported
cases occurred prior to 1991, before hepatitis B vaccination was widely used
and before standard (universal) infection control precautions were
implemented.  These mostly involved infected surgeons or dentists who
transmitted during the performance of invasive procedures (45-67).  However,
other healthcare providers also have been implicated in HBV transmission to
patients (61,62,68-70).  Most of these involved skin conditions in these
healthcare providers (e.g., exudative dermatitis, bleeding lesions or cuts)
that contributed to transmission. Substantially fewer episodes of HBV
transmission to patients from infected surgeons have been reported worldwide
since 1991, most of which were from the United Kingdom (10,71,72).   All but
one of the cases in the United Kingdom involved healthcare providers who
were infected with precore mutations and were negative for HBeAg (10).

Transmission of HBV via transfusion of blood and plasma-derived products has
been eliminated in most countries through donor screening for HBsAg and
viral inactivation procedures.  However, transmission also occurs with
inadequately sterilized needles and medical instruments, the reuse of
disposable needles and syringes, and contamination of multiple dose
medication vials.  Contaminated environmental surfaces have been a major
source for HBV transmission among chronic hemodialysis patients (73). HBV
transmission among hemodialysis patients is consistently associated with the
presence of a chronically infected patient, failure to dialyze that patient
in a separate room using dedicated equipment and staff, and failure to
vaccinate patients against hepatitis B.

In developing countries, transmission through contaminated injection
equipment remains a significant problem because of the difficulty in
obtaining disposable needles and syringes and the lack of means to
adequately sterilize reusable equipment (13).  In developed countries,
episodes of HBV transmission from one patient to another in healthcare
settings also have been reported (14-17,74-77).  In most cases, these
transmissions resulted from noncompliance with recommended infection control
practices that were designed to prevent cross-contamination of medical
equipment and devices.

The primary goal of hepatitis B prevention programs is reduction of
HBV-related chronic liver disease and chronic HBV infection.  A secondary
goal is the prevention of acute hepatitis B.  HBV infection can be prevented
by screening blood, plasma, organ, tissue, and semen donors, virus
inactivation of plasma-derived products, risk-reduction counseling and
services, and implementation and maintenance of infection control practices.
Although such activities can reduce or eliminate the potential risk for HBV
transmission, by far the single most effective prevention measure is

In 1992, the World Health Organization recommended that all countries
include hepatitis B vaccine in their routine infant immunization programs.
In 2000, only 116 of 215 countries have such a policy, representing 31% of
the global birth cohort.  Thus, despite the availability of an effective
vaccine for more than 15 years, most of the worlds children remain at risk
for HBV infection.

Immunization strategies in developed countries vary widely. In the United
States, the immunization strategy has evolved over time and now includes 1)
prevention of perinatal HBV infection through routine screening of all
pregnant women and appropriate postexposure immunoprophylaxis of infants
born to HBsAg positive women; 2) routine vaccination of infants; 3) routine
vaccination of adolescents who have not previously been vaccinated; and 4)
vaccination of adults at increased risk of infection (78,79).  Most
countries in western Europe have focused efforts on prevention of perinatal
infection and routine vaccination of adolescents; rarely, routine
immunization of infants also has been included (80-84).  In eastern European
countries, routine immunization of infants has been the primary strategy

The success of routine immunization of children and adolescents in
interrupting HBV transmission already has been demonstrated in both high and
low HBV endemic areas. During the 15 years after routine childhood hepatitis
B immunization was implemented in Taiwan, the prevalence of chronic HBV
infection among children <15 years old declined from 10% to 0.7%, a decrease
of 93%, and rates of HCC among children 6-14 years old declined by 50%
(86,87).  Similarly, almost a 90% decline was observed in the overall
prevalence of infection (as measured by antibody to hepatitis B core
antigen), while prevalence of protective antibody (antibody to hepatitis B
surface antigen) remained high. In countries such as Italy and the United
States, the incidence of acute hepatitis B has declined dramatically during
the past decade, particularly among persons in younger age groups

The integration of vaccine into existing childhood vaccination schedules has
the greatest likelihood of successfully lowering the disease incidence.
There is already an established infrastructure for vaccine delivery to
children which can ensure high coverage levels, and the hepatitis B vaccine
has been shown to provide long-term protection against chronic HBV
infection. In addition, routine infant immunization ensures the prevention
of HBV infections in subpopulations that have high rates of early childhood
infection (e.g., infants and children of immigrant women from high
endemicity areas). The addition of routine adolescent vaccination achieves a
more rapid reduction in HBV transmission.

However, until the cohorts of vaccinated children reach adolescence and
adulthood, efforts must be strengthened to vaccinate older adolescents and
adults with high-risk behaviors or occupations. Most HBV transmission and
the morbidity associated with acute hepatitis B occurs among older
adolescents and young adults, and most of these infections result from
sexual transmission. Adults at highest risk for infection are the most
difficult to reach with vaccine and a substantial proportion do not
self-identify as belonging to a risk group. There are long-standing
recommendations to vaccinate persons who report a history of multiple sex
partners, treatment for a sexually transmitted disease, men who have sex
with men and injecting drug users. However, vaccine is rarely offered in
settings that provide health-care to adults. Although continued immunization
of successive birth cohorts should achieve the eventual elimination of HBV
transmission, this will not occur for decades without successful vaccination
adults at increased risk for infection.