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Epidemiology, transmission, and prevention of hepatitis B

virus infection
Authors: Eng-Kiong Teo, MD, Anna SF Lok, MD
Section Editors: Sheldon L Kaplan, MD, Rafael Esteban, MD
Deputy Editor: Jennifer Mitty, MD, MPH

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jun 2020. | This topic last updated: Aug 21, 2018.

INTRODUCTION

Hepatitis B virus (HBV) infection is a global public health problem. It is estimated that there are 248
million HBV carriers in the world, of whom roughly 600,000 die annually from HBV-related liver
disease [1,2]. The implementation of effective vaccination programs in many countries has resulted
in a significant decrease in the incidence of new hepatitis B infection. Nevertheless, HBV infection
remains an important cause of morbidity and mortality.

The spectrum of clinical manifestations of HBV infection varies in both acute and chronic disease.
During the acute phase, manifestations range from subclinical or anicteric hepatitis to icteric
hepatitis and, in some cases, fulminant hepatitis. During the chronic phase, manifestations range
from an asymptomatic carrier state to chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
Extrahepatic manifestations also can occur with both acute and chronic infection.

This topic review will discuss the epidemiology, modes of transmission, and prevention of HBV
infection. The clinical manifestations and natural history of HBV infection as well as hepatitis B
vaccination are discussed in detail separately. (See "Hepatitis B virus: Clinical manifestations and
natural history" and "Hepatitis B virus immunization in adults".)

EPIDEMIOLOGY OF CHRONIC HBV

It is estimated that approximately two billion people worldwide have evidence of past or present

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infection with hepatitis B virus (HBV), and 248 million individuals are chronic carriers (ie, positive
for hepatitis B surface antigen [HBsAg]) [2,3]. The overall prevalence of HBsAg is reported to be
3.6 percent; however, it varies depending upon the geographic area. The prevalence of chronic
HBV ranges from <2 percent in low-prevalence areas (eg, United States, Canada, Western
Europe) to 2 to 7 percent in intermediate-prevalence areas (eg, Mediterranean countries, Japan,
Central Asia, Middle East, and parts of South America) to ≥8 percent in high-prevalence areas (eg,
Western Africa, South Sudan) (table 1) [2-4].

The wide range in the prevalence of patients with chronic HBV in different parts of the world is
largely related to differences in the age at infection, which is inversely related to the risk of
chronicity. The rate of progression from acute to chronic HBV infection is approximately 90 percent
for perinatally acquired infection [5], 20 to 50 percent for infections between the age of one and
five years [6,7], and less than 5 percent for adult-acquired infection [6].

In areas of low prevalence, many of the patients who have chronic HBV were born in areas where
the prevalence is higher [8-14]. As an example, in an analysis of the National Health and Nutrition
Examination Survey (NHANES; which includes data from approximately 20,000 persons), the
prevalence of chronic HBV in the United States from 2007 to 2012 was estimated to be 0.3
percent; however, the prevalence among foreign-born non-Hispanic blacks during the same period
was 2.5 percent [13]. In addition, from 2011 to 2012, the prevalence among non-Hispanic Asians
(most of whom were foreign born) was estimated to be 3.1 percent, accounting for approximately
50 percent of chronic HBV cases in the United States during that time period. In another study that
evaluated 1615 adults with chronic HBV from across the United States and in Toronto, Canada,
only 18 percent were born in North America; of those who were born outside North America, most
were from Asia (67 percent) and Africa (11 percent) [9]. In 2013, viral hepatitis, primarily due to
HBV and hepatitis C virus, was the seventh leading cause of death worldwide [15]. Most mortality
was attributable to liver cancer and cirrhosis. Globally, the total number of deaths due to hepatitis B
in 2013 was estimated to be 686,000 [16]. In the United States, the rate of HBV-related mortality
from 2009 to 2013 was 0.5 deaths/100,000 population [17]; among the various subpopulations,
HBV-related mortality was highest among Asians and Pacific Islanders at 2.6 deaths/100,000
population. In China, the age-standardized death rate for HBV-related liver cancer and cirrhosis in
2013 was 10.95 and 4.91 per 100,000 people, respectively [18].

TRANSMISSION OF HBV

Hepatitis B virus (HBV) is transmitted from patients who are infected to those who are not immune
(ie, hepatitis B surface antibody [anti-HBs]-negative). Hepatitis B vaccination has significantly

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reduced the risk of transmission worldwide. (See "Hepatitis B virus immunization in adults" and
"Hepatitis B virus immunization in infants, children, and adolescents".)

The predominant mode of HBV transmission varies in different geographical areas. Mother-to-child
transmission is the predominant mode of transmission in high-prevalence areas [19,20]. In
comparison, horizontal transmission, particularly in early childhood, accounts for most cases of
chronic HBV infection in intermediate-prevalence areas, while unprotected sexual intercourse and
injection drug use in adults are the major routes of spread in low-prevalence areas (table 1) [21].

In the United States, the incidence of acute HBV decreased by 81 percent from 1990 to 2006; the
greatest decline was among children and adolescents [7]. From 2006 to 2013, the incidence of
HBV infection generally remained stable at 1 case per 100,000 persons, with an estimated 19,764
newly infected patients in 2013 [17]. Rates were highest in adults, particularly males aged 25 to 44
years. However, during this period, the incidence of acute HBV infection increased in three states
(Kentucky, Tennessee, and West Virginia); the greatest increase occurred in non-urban counties,
and most were associated with drug use [22,23]. Prior reports had identified sexual exposure (eg,
sexual contact with a person known to have HBV, multiple sex partners, men who have sex with
men) as the most common risk factor for HBV transmission in adults in the United States [7].

This section will review the different modes of transmission. A detailed discussion on prevention is
found below. (See 'Prevention' below.)

Mother-to-child transmission — The infection rate of infants born to hepatitis B surface antigen
(HBsAg)-positive mothers is as high as 90 percent among infants who do not receive hepatitis B
immune globulin and hepatitis B vaccination at birth [5]. Mother-to-child transmission may occur in
utero, at the time of birth, or after birth. However, most infections occur at the time of birth. (See
"Hepatitis B and pregnancy", section on 'Mother-to-child transmission'.)

Passive and active immunization of the newborn within 12 hours of delivery has reduced the risk of
HBV transmission by more than 95 percent. However, despite the proper use of prophylaxis,
transmission can still occur. The risk appears to be greatest if the mother is positive for hepatitis B
e antigen (HBeAg) and/or has a high HBV viral load. Among women with a high viral load, antiviral
therapy for the mother can further reduce the risk of transmission. Detailed discussions on
preventing mother-to-child transmission are found elsewhere. (See 'Mother-to-child transmission'
below and "Hepatitis B virus immunization in infants, children, and adolescents" and "Hepatitis B
and pregnancy", section on 'Prevention of mother-to-child transmission'.)

Breastfeeding — Breastfeeding does not appear to increase the risk of transmission. A

discussion of breastfeeding among HBV-infected women is found elsewhere. (See "Hepatitis B

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and pregnancy", section on 'Breastfeeding and transmission'.)

Paternal transmission — Transmission of HBV from fathers to their infants is possible based
upon genotypic and phylogenetic analysis. In a study conducted in Taiwan, the HBV infection rate
was 65 percent among neonates born to HBsAg-negative mothers and HBsAg-positive fathers
[24]. Most of these transmissions are believed to result from close contact of the unprotected
infants with the infected blood and body fluids of the fathers. Although some studies have detected
HBV in sperm, there is no clinical evidence to support that infected sperm result in transmission of
HBV infection to the fetus [25-28].

Transfusion — The World Health Organization suggests screening with both HBsAg and hepatitis
B core antibody (anti-HBc) [29]. The risk of HBV transmission through blood transfusions was
significantly reduced after the introduction of serologic screening of donors for HBsAg [30]. The
risk was further reduced by screening for anti-HBc in addition to HBsAg. Anti-HBc can be detected
during the widow phase when HBsAg is not present. (See "Hepatitis B virus: Clinical
manifestations and natural history", section on 'Acute hepatitis'.)

In the United States, the residual risk of HBV transmission after screening for both HBsAg and
anti-HBc ranged from approximately 1 in 280,000 to 1 in 357,000 donations [31]. This risk has
been further reduced by the addition of HBV DNA screening. In 2009, the United States added
HBV DNA to blood donor screening. HBV DNA is tested by mini-pool nucleic acid testing (MP-
NAT); if NAT testing is positive in the mini-pool, the individual samples are further evaluated. The
practice of testing for HBV nucleic acid as part of MP-NAT screening has lowered the risk of HBV
transmission through transfusions to 1 in 1 million [32].

Some countries, including Singapore, Spain, and Germany, are also using NAT for screening of
HBV infection. However, the implementation of NAT in countries with high prevalence, where mini-
pool testing would identify HBV in as many as 9.5 per million donations [33], is hampered by the
cost involved. An additional discussion on blood donor screening is found elsewhere. (See "Blood
donor screening: Laboratory testing", section on 'Infectious disease screening'.)

Sexual transmission — Sexual transmission remains a common source of HBV transmission

[17,22,34]. As an example, in one report that evaluated 2220 cases of acute HBV infection in the
United States, sexual risk was believed to account for HBV transmission in approximately 35
percent of the cases [22]. Unvaccinated men who have sex with men and heterosexual persons
who have multiple sex partners or contact with sex workers are at particularly high risk [34]. In the
United States, sexual transmission had been considered the primary source of transmission [7];
however, from 2006 to 2011, most new cases of acute HBV were associated with drug use [22].

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Percutaneous inoculation — Percutaneous transmission usually happens among injection drug

users (IDU) who share syringes and needles. A systematic review, which evaluated data from 59
countries, estimated that there were 6.4 million injection drug users who were anti-HBc positive,
and 1.2 million who were HBsAg positive in 2010 [35]. In the United States, drug use has been
reported to be the primary risk factor for HBV transmission in recent years [22,23]. The risk of HBV
transmission increases with number of years of drug use, frequency of injection, and sharing of
drug preparation equipment [36-38]. In addition to drug use, certain practices such as
acupuncture, tattooing, and body piercing have also been associated with transmission of HBV
through the use of equipment that is contaminated with HBV-infected blood [34].

Nosocomial infection — HBV can be transmitted in the health care setting [39,40]. Transmission
generally occurs from patient to patient or from patient to health care providers (HCP) via
contaminated instruments or an accidental needle stick. The number of HBV infections among
HCP has declined significantly, due in large part to efforts aimed at immunizing all HCP against
HBV and using postexposure prophylaxis for nonimmune persons (ie, those who are unvaccinated
or vaccine nonresponders). Among individuals who are not immune to HBV, the risk of
transmission depends upon the HBsAg, HBeAg, and HBV DNA status of the source. (See
"Immunizations for health care providers" and "Prevention of hepatitis B virus and hepatitis C virus
infection among health care providers".)

Although uncommon, transmission can also occur from an infected HCP to a nonimmune patient.
Transmission usually results from unsafe injection practices, which often could have been avoided
with standard precautions and appropriate aseptic techniques [41]. However, several reports have
demonstrated that transmission can occur even when such policies are followed [42-44]. As an
example, in a case series from 1996 to 2002, there were reports of 12 infected HCP infecting a
total of 91 patients [44]. The risk of HBV transmission from infected HCP depends upon the
HBeAg status and the HBV DNA level of the infected provider. Transmission has generally been
considered to be greatest among patients with chronic HBV who are HBeAg positive [45] and can
occur in patients with a wide range of HBV DNA levels. Transmission from an HCP to a patient is
most likely to occur when the HBV DNA level is more than 1.9 x 105 international units/mL [46];
however, HBV transmission has also been reported when the HBV DNA level of the HCP was
approximately 8000 international units/mL [47,48].

Transplant recipients — HBV infection can be transmitted from HBsAg-positive donors to HBsAg-
negative recipients, with severe clinical consequences when the recipient is nonimmune (ie, anti-
HBs-negative). (See "Infection in the solid organ transplant recipient", section on 'HIV, HTLV, and
hepatitis viruses' and "Overview of infections following hematopoietic cell transplantation".)

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Transmission of HBV infection has been reported after hematopoietic stem cell and solid organ
transplantation. Among solid organ transplant recipients, the risk of post-transplant HBV infection
is seen primarily among seronegative liver recipients [49]; however, cases have also been reported
among those who received extrahepatic organs such as kidneys and even avascular tissues such
as corneas from HBsAg-positive donors [50,51]. Among organ transplant patients, transmission
has also been reported when the donor had isolated anti-HBc [52]. (See "Hepatitis B virus:
Screening and diagnosis", section on 'Isolated anti-HBc'.)

Other modes of transmission — Adults and children may acquire HBV infection via blood
exposure to minor breaks in the skin or mucous membranes. In addition, transmission can occur
via exposure to household articles that have been contaminated with blood, such as toothbrushes,
razors, and toys, since HBV can survive outside the human body for a prolonged period [53].
Although HBV DNA has been detected in various bodily secretions of hepatitis B carriers, there is
no firm evidence of HBV transmission via body fluids other than blood or semen. (See "Prevention
of hepatitis B virus and hepatitis C virus infection among health care providers", section on
'Epidemiology of bloodborne exposures'.)

PREVENTION

Pre-exposure vaccination — Vaccination against hepatitis B virus (HBV) prior to an exposure is

the best way to prevent HBV infection. Universal vaccination of newborns is recommended in most
countries. Vaccination should also be provided to individuals who are not immune to HBV and are
at high risk of exposure or a poor disease outcome (eg, health care personnel, injection drug
users, household contacts of hepatitis B surface antigen [HBsAg]-positive patients, men who have
sex with men, human immunodeficiency virus [HIV]-infected patients, hepatitis C virus [HCV]-
infected patients). More detailed discussions on hepatitis B vaccination are found elsewhere. (See
"Hepatitis B virus immunization in adults" and "Immunizations for patients with chronic liver
disease" and "Prevention of hepatitis B virus infection in the HIV-infected adult" and "Hepatitis B
virus immunization in infants, children, and adolescents".)

Postexposure prophylaxis — Postexposure prophylaxis to prevent HBV infection should be

considered for individuals who have had an exposure that could potentially transmit HBV. These
include percutaneous (eg, bite or needlestick) or mucosal exposures to blood or infectious
secretions (eg, semen, body fluids that contain blood) of a patient who is HBsAg positive or whose
HBsAg status is unknown.

The need for postexposure prophylaxis and the type of prophylaxis depend upon the vaccination

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history and hepatitis B surface antibody (anti-HBs) status of the exposed patient and the HBsAg
status of the source patient. A detailed discussion of postexposure prophylaxis is found elsewhere.
(See "Management of nonoccupational exposures to HIV and hepatitis B and C in adults", section
on 'Exposure to hepatitis B virus'.)

Management of special populations — Pre-exposure hepatitis B vaccination is the best way to

prevent HBV transmission. However, for certain groups of patients, additional strategies are also
used. An overview of these strategies are provided below.

Mother-to-child transmission — To reduce mother-to-child transmission, infants born to

mothers who are HBsAg positive should receive active and passive immunization (ie, hepatitis B
vaccine and hepatitis B immune globulin [HBIG]) as soon as possible and preferably within 12
hours of birth. In addition, administering antiviral therapy to mothers with high HBV viral loads can
further reduce the risk of infection in the newborn. A more detailed discussion on preventing HBV
transmission during pregnancy is found elsewhere. (See "Hepatitis B and pregnancy".)

Sexual exposure — HBsAg-positive patients should use condoms to reduce the risk of sexual
transmission of HBV if their partner is not immune or if their partner's immune status is unknown.
In addition, spouses and steady sex partners of a patient with chronic HBV should be screened to
see if they have been previously infected. Those who are not immune and are without evidence of
chronic HBV should be vaccinated and immunity verified by testing for anti-HBs one to two months
after completing the course of vaccination. (See "Prevention of sexually transmitted infections" and
"Hepatitis B virus immunization in adults".)

Percutaneous — To prevent percutaneous transmission of HBV (via drug use or piercings),

patients should be educated about the use of sterile disposable needles and equipment. In
addition, for injection drug users, it is important to address the underlying substance use disorder.
(See "Pharmacotherapy for opioid use disorder" and "Psychosocial interventions for stimulant use
disorder in adults".)

Health care providers — Health care providers (HCP) should be immunized against HBV. In
addition, HCP should be trained in techniques to minimize the risk of exposure to bloodborne
pathogens. A detailed discussion of HBV prevention in HCP is found elsewhere. (See "Prevention
of hepatitis B virus and hepatitis C virus infection among health care providers" and
"Immunizations for health care providers", section on 'Hepatitis B vaccine'.)

To minimize transmission of HBV from an infected HCP to an uninfected patient, guideline panels
have put forth recommendations regarding the types of procedures HCP can perform based upon
the hepatitis B e antigen (HBeAg) and HBV DNA status of the infected provider [47,54-56]. As an

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example, in the United States, Centers for Disease Control and Prevention guidelines state that
HBV-infected providers can conduct exposure-prone procedures if their HBV viral load is
confirmed to be ≤1000 international units/mL or undetectable (spontaneously or while receiving
antiviral therapy) on regular testing performed at least every six months [47]. Exposure-prone
procedures include major abdominal, cardiothoracic, and orthopedic surgery, repair of major
traumatic injuries, abdominal and vaginal hysterectomy, caesarean section, vaginal deliveries, and
major oral or maxillofacial surgery. However, if a percutaneous exposure should occur, the
uninfected patient should still receive postexposure prophylaxis. (See 'Postexposure prophylaxis'
above.)

Transplant recipients — To help prevent HBV transmission to solid and hematopoietic

transplant recipients, donors are routinely screened for HBsAg. In some countries, donors are also
screened for anti-HBc and HBV DNA. It is unclear if testing donors for HBV DNA reduces the risk
of HBV transmission to recipients. As an example, in a report from France that included 11,115
consecutive organ, tissue, and cell donors, HBV DNA was only detected in 0.07 percent of
individuals without serologic markers for chronic HBV [57]. Thus, serologic testing is still the
mainstay of screening [58].

Transmission of HBV infection can occur from HBsAg-negative, anti-HBc-positive donors to non-
immune recipients, particularly in the setting of liver transplantation. To reduce this risk,
prophylactic antiviral therapy is recommended.

The use of HBsAg-positive or HBV DNA-positive donors should be avoided for HBV-naïve
recipients if a suitable donor without HBV is available. However, in situations where this is not
possible, treatment of the donor and/or recipients with antiviral therapy and HBIG may help
decrease the risk of transmission.

More detailed discussions on preventing HBV in transplant patients are found elsewhere. (See
"Prevention of viral infections in hematopoietic cell transplant recipients", section on 'Hepatitis
viruses' and "Liver transplantation for chronic hepatitis B virus infection", section on 'Prevention of
HBV reinfection' and "Kidney transplantation in adults: Hepatitis B virus infection in kidney
transplant recipients", section on 'Risk factors for de novo HBV infection following transplantation'.)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions around
the world are provided separately. (See "Society guideline links: Hepatitis B vaccination" and
"Society guideline links: Immunizations in children and adolescents" and "Society guideline links:

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Immunizations in adults" and "Society guideline links: Prevention of hepatitis B virus and hepatitis
C virus infection among health care providers".)

SUMMARY AND RECOMMENDATIONS

● It is estimated that approximately two billion people worldwide have evidence of past or
present infection with hepatitis B virus (HBV), and 248 million individuals are chronic carriers
(ie, positive for hepatitis B surface antigen [HBsAg]). The overall prevalence of HBsAg is
reported to be 3.6 percent; however, it varies depending upon the geographic area (table 1).
(See 'Epidemiology of chronic HBV' above.)

● The predominant mode of HBV transmission varies in different geographical areas. Mother-to-
child infection is the predominant mode of transmission in high-prevalence areas. In
comparison, horizontal transmission, particularly in early childhood, accounts for most cases
of chronic HBV infection in intermediate prevalence areas. Unprotected sexual intercourse
and injection drug use in adults are the major routes of spread in low-prevalence areas. (See
'Transmission of HBV' above.)

● Vaccination against HBV prior to an exposure is the best way to prevent HBV infection.
Universal vaccination of newborns is recommended in most countries. Vaccination should also
be provided to individuals who are not immune to HBV and are at high risk of exposure or a
poor disease outcome. (See 'Pre-exposure vaccination' above.)

● Additional strategies (eg, postexposure prophylaxis, antiviral therapy), can be used to help
prevent HBV transmission to certain groups of high-risk patients who are not immune (eg,
infants of HBsAg-positive mothers, sex and drug-using partners of patients who are HBsAg
positive, transplant recipients). (See 'Prevention' above.)

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GRAPHICS

Epidemiology and modes of transmission of hepatitis B virus infection

High Intermediate Low

Carrier rate ≥8% 2 to 7% ≤1%

Geographic Parts of sub-Saharan Africa Mediterranean basin; Eastern United States; Canada;
distribution* (eg, Western Africa, South Europe; Central Asia; Western Europe; Mexico;
Sudan) Southeast Asia; China; Japan; Australia; New Zealand
parts of Latin and South
America (eg, Peru, Colombia);
Middle East

Predominant Perinatal and early childhood Early childhood Adult

age at
infection

Predominant Mother to child; percutaneous Percutaneous; sexual Percutaneous; sexual

mode of
infection

* For updated data, refer to the United States Centers for Disease Control and Prevention website.

References:
1. Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: New estimates of
age-specific HBsAg seroprevalence and endemicity. Vaccine 2012; 30:2212.
2. Schweitzer A, Horn J, Mikolajczyk RT, et al. Estimations of worldwide prevalence of chronic hepatitis B virus
infection: A systematic review of data published between 1965 and 2013. Lancet 2015; 386:1546.
3. HIV, viral hepatitis and sexually transmissible infections in Australia: Annual Surveillance Report 2013. Sydney: The
Kirby Institute, The University of New South Wales; 2013.
4. New Zealand Society of Gastroenterology. www.nzsg.org.nz/cms2/research/hepatitis/hepatitis b/ (accessed
12/31/2015).

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