Epidemiology, transmission and prevention of hepatitis B virus infection (Eng Kiong Teo MD et al.)

Written by :

Eng-Kiong Teo, MD.   Research Fellow  University of Michigan Medical School
Anna SF Lok, MD.  Professor of Medicine  University of Michigan Medical School

UpToDate performs a continuous review of over 290 journals and other resources. Updates are added as important new information is published. The literature review for UpToDate version 11.1 is current through December 2002; this topic was last changed on November 18, 2002.

Hepatits B virus (HBV) infection is a global public health problem. It is estimated that there are more than 300 million HBV carriers in the world, of whom over 250,000 die annually from HBV-related liver disease [1]. Furthermore, the rate of HBV-related hospitalizations, cancers, and deaths in the United States have more than doubled during the past decade [2]. This may be due to the delay in implementation of universal vaccination (which was instituted in 1991), the influx of immigrants from endemic areas, improved diagnosis, and better documentation of infection. Thus, although HBV can be prevented by vaccination, it remains an important cause of morbidity and mortality in the United States. 

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 are discussed separately. This topic is also discussed in an official guideline issued by the American Association for the Study of Liver Diseases.

EPIDEMIOLOGY — The prevalence of HBV carriers varies from 0.1 percent to 2 percent in low prevalence areas (United States and Canada, Western Europe, Australia and New Zealand), to 3 to 5 percent in intermediate prevalence areas (Mediterranean countries, Japan, Central Asia, Middle East, and Latin and South America), to 10 to 20 percent in high prevalence areas (southeast Asia, China, sub-Saharan Africa) [1, 3].

The wide range in HBV carrier rate 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 [4], 20 to 50 percent for infections between the age of 1 and 5 years [5, 6], and less than 5 percent for adult acquired infection [7].
 

MODES OF TRANSMISSION — The mode of transmission of HBV varies in part with the prevalence of infection. Perinatal infection is the predominant mode of transmission in high prevalence areas [4, 6]. 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 intravenous drug use in adults are the major routes of spread in low prevalence areas [3].

Perinatal transmission — The infection rate among infants born to HBeAg-positive mothers is as high as 90 percent [4]. Maternal-infant transmission may occur in utero, at the time of birth, or after birth. The high protective efficacy of (95 percent) of neonatal vaccination suggests that infection occurs predominantly at or after birth. There is no evidence that cesarean section prevents maternal-infant transmission. Breast-feeding does not appear to increase the risk of transmission. Although HBV DNA has been detected in the colostrum of HBsAg positive mothers, a study on 147 infants born to carrier mothers revealed no evidence for a relationship between breast-feeding and the subsequent development of chronic HBV infection in the babies [8]. Transplacental passage of HBV is very rare. The risk of transmission during amniocentesis is also low, particularly in mothers who are HBeAg negative and when the procedure is done using a 22-gauge needle under continuous guidance [9].
 

The high frequency of perinatal transmission in endemic areas is probably related to the high prevalence (40 to 50 percent) of HBeAg in women of reproductive age. These women remain infectious because of the slow rate of HBeAg seroconversion during the first two decades of life. Studies in Chinese children, for example, have found HBeAg in as many as 90 percent below the age of 5, and up to 80 percent below the age of 20 [10, 11]. The cumulative rate of spontaneous HBeAg clearance is estimated to be only 15 percent after 20 years of infection, leaving many women of childbearing age still infectious [12, 13].

The risk of maternal-infant transmission is related to the HBV replicative status of the mother. It is 85 to 90 percent in infants born to HBeAg positive mothers and 32 percent in infants born to HBeAg negative mothers [14]. A survey in an urban South-East Asia country estimated the overall risk of perinatal transmission in all HBsAg positive mothers to be 40 percent [15]. More recent studies have demonstrated that maternal serum HBV DNA levels correlate better with the risk of transmission. In a study of 773 HBsAg positive mothers in Taiwan, the odds ratio for having an infected infant increased from 1 to 147 as the maternal serum HBV DNA levels increased from 5 pg/mL to >1400 pg/mL [16].

Maternal carrier testing should be performed on all women at the first prenatal visit and repeated late in pregnancy in those at high risk for HBV infection. The current recommendation is to provide passive-active immunization to newborns of carrier mothers. Cesarean section should not be routinely recommended for carrier mothers. Infants who have been vaccinated may be breast-fed [17], but carrier mothers should not participate in donating breast milk.
 

Horizontal transmission — Children may acquire HBV infection through horizontal transmission via minor breaks in the skin or mucous membranes or close bodily contacts with other children. In addition, HBV can survive outside the human body for a prolonged period; as a result, transmission via contaminated household articles such as toothbrushes, razors, and even toys may be possible. 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.

Transfusion — The incidence of transfusion-related hepatitis B decreased significantly after the exclusion of paid blood donors and the introduction of hepatitis B surface antigen (HBsAg) screening of donors [13]. In the United States, both HBsAg and anti-HBc (hepatitis B core antigen) are used for donor screening. Anti-HBc was initially used as a surrogate marker for non-A, non-B hepatitis virus but has been retained after implementation of hepatitis C testing to detect donors who are in the window phase during recovery from acute hepatitis B) or who have low level chronic HBV infection. The window phase remains an important issue since an anonymous survey of almost 35,000 blood donors in the United States found that 0.4 percent admitted to a high-risk behavior within the three months before blood donation [18].

The practical value of anti-HBc screening is not clear because of the low specificity of the test, the low incidence of transfusion-associated HBV infection in low prevalence areas, and the need to exclude as many as 22 percent of the donor population in high prevalence areas [13, 19]. The current risk of donating blood during the window period and therefore of posttransfusion hepatitis B is estimated to be 1 in 63,000 in the United States [20]. Patients requiring multiple transfusions, such as hemophiliacs and thalassemics, are at increased risk of contracting HBV infection.

Sexual transmission — Sexual transmission remains the major mode of spread of HBV in developed countries [1, 3]. It is estimated that sexual transmission accounts for more than 50 percent of acute hepatitis B in the United States [21]. The incidence of acute hepatitis B associated with homosexual activity decreased from 20 percent in 1982 to 7 percent in 1988 as a result of education on safe sex practice to prevent human immunodeficiency virus infection. During the same period, the incidence of acute hepatitis B increased from 15 to 27 percent in subjects with heterosexual promiscuity or parenteral drug use [21]. Sexual transmission of hepatitis B can be prevented by vaccination of spouses and steady sex partners in individuals with monogamous partners, and safe sex practice including use of condoms in subjects with multiple partners.

Percutaneous inoculation — Percutaneous transmission usually happens among intravenous drug users who share syringes and needles. Household contacts can also transmit hepatitis B through the sharing of razors or toothbrushes. Certain practices like acupuncture, tattooing, and body piercing have also been associated with transmission of hepatitis B. Public health education and the use of disposable needles or equipment are important in preventing this mode of transmission.

Nosocomial infection — HBV is the most commonly transmitted blood-borne virus in the healthcare setting [22]. Transmission generally occurs from patient to patient or from patient to health care personnel via contaminated instruments or accidental needle stick. Healthcare workers, particularly surgeons, pathologists, and physicians working in hemodialysis and oncology units, have the highest risks of HBV infection.

Despite the publicity about hepatitis B transmission from healthcare workers to patients, this mode of spread is extremely rare. Transmission of hepatitis B from patients to healthcare workers is far more common as illustrated by the high prevalence of HBV serological markers in surveillance studies performed in the 1970s and 1980s [23]. One outbreak was traced to a cardiothoracic surgeon despite adequate infection control during the operations [24]. Transmission was traced to tears in gloves and cuts on the surgeon’s fingers during prolonged suturing.

In 1993, the Viral Hepatitis Prevention Board formulated a seven point consensus to contain hepatitis B as an occupational hazard [25]. In addition to vaccination of healthcare workers, a number of infection control measures was recommended and enforcement of these measures is monitored by the United States Occupational Safety and Health Administration (OSHA). OSHA regulations can be viewed on the World Wide Web. (http://www.osha.gov/comp-links.html).

Nosocomial transmission can be prevented by screening of blood and blood products, use of disposable needles and equipment, proper sterilization of surgical instruments, enforcement of infection control measures and vaccination of healthcare workers. In many developed countries, guidelines have been established to defined the parameters in which healthcare providers with hepatitis B can operate. In the United Kingdom, healthcare workers who are positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) must stop “exposure-prone procedures,” while health care workers who are HBsAg positive but HBeAg negative may continue their usual work unless they have been associated with transmission of hepatitis B to patients [26]. The Society for Healthcare Epidemiology of America recommended that HBeAg positive healthcare workers should routinely wear double gloves and should not perform activities that have been identified epidemiologically as associated with a risk for provider-to-patient hepatitis B transmission [27].

The difference in the scope of permissible work between HBeAg positive versus HBeAg negative HBV carriers is related to the traditional concept that HBeAg is a reliable marker of infectivity. However, one report documented the transmission of hepatitis B from four HBsAg positive, HBeAg negative surgeons to five patients [28]. All the surgeons were infected with hepatitis B virus that had a precore stop codon mutation resulting in non-expression of HBeAg despite active HBV replication [29, 30]. This incident raised questions regarding the accuracy of HBeAg as a marker for infectivity. Although measurement of HBV DNA has been proposed as a more sensitive marker, HBV DNA assays are not standardized, can fluctuate, and be intermittently undetectable in patients with chronic HBV infection. Thus, until further data are available, current recommendations on the scope of permissible work by HBsAg positive healthcare workers will remain unchanged.
 

Organ transplantation — Organ donors are routinely screened for HBsAg. Transmission of HBV infection has been reported after transplantation of extrahepatic organs, such as kidneys and even cornea, from HBsAg positive donors. The role of anti-HBc in organ donor screening is less certain because of the possibility of false positive results, the potential loss of up to 5 percent of donors even in low endemic areas, and the uncertainty about the infectivity of organs, especially extrahepatic organs, from donors who have isolated anti-HBc [31, 32, 33, 34]. The risk of using livers from such donors is significantly higher as illustrated by the following reports:

POSTEXPOSURE PROPHYLAXIS — Post exposure prophylaxis is recommended for all non vaccinated individuals who are exposed to blood or infectious secretions. The first dose vaccine should be given as early as possible within 12 hours of exposure while administering one dose of HBIG at the same time in another site. The other two doses of vaccine should be administered according to the usual schedule, although data supporting this recommendation are not available. In individuals who have been vaccinated and have a documented response, no post-exposure prophylaxis is required. Individuals who have no post-vaccination testing will require a second course of vaccination unless anti-HBs is detectable at the time of exposure. Individuals who are documented to be non-responders will require two doses of HBIG given one month apart.

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