Hepatitis B virus (HBV) infection is highly prevalent worldwide and is a major cause of morbidity and death. Two billion people globally have been infected with HBV, 350 to 400 million are chronic carriers, and tens of millions of new cases occur annually. Of those infected, 15% to 40% develop HBV complications, namely cirrhosis or hepatocellular carcinoma (HCC).1–3
The high prevalence of HBV infection represents an enormous failure of public health, considering that HBV immunization has been available for an entire generation, and where it has been employed it has been highly effective at reducing the incidence of HBV infection. Immunization, however, has been underused.
This supplement to the Cleveland Clinic Journal of Medicine, derived from a live symposium, aims to enhance awareness of the natural history of HBV infection and clarify its management recommendations with illustrative case histories. The supplement starts with a brief review of HBV terminology, natural history, and epidemiology.
CHRONIC HBV INFECTION TERMINOLOGY
Familiarity with the terms commonly used to describe chronic HBV infection will help clinicians in the management of the disease4:
- Chronic HBV infection is defined as presence of hepatitis B surface antigen (HBsAg) for more than 6 months. Those with infection may also express another antigen, HB e antigen (HBeAg), a marker of heightened infectivity. At the same time, those who are HBeAg positive are better responders to antiviral therapy compared with those who are HBeAg negative.
- An inactive HBsAg carrier is an individual who is HBsAg positive with a very low level of circulating virus, liver enzyme levels within normal limits, and a low likelihood of having chronic progressive disease.
- Resolved HBV infection is defined as previous HBV infection with no remaining evidence of active disease. Such individuals test negative for HBsAg and positive for antibody to HBsAg (anti-HBs) and to HB core antigen (anti-HBc). They also have no detectable viral load, or HBV DNA, in their blood. In most instances, they are protected from reinfection.
- Reactivation is the reappearance of HBV infection in someone who is known to be an inactive HBsAg carrier or whose previous HBV infection had resolved (see “Case: Recurrence despite anti-HBs and HBsAg negativity”).
- HBeAg seroconversion is the transition from HBeAg-positive to HBeAg-negative status and development of antibody to HBeAg (anti-HBe), usually accompanied by less active liver disease and lower viral loads.
- HBeAg clearance is disappearance of HBeAg without the development of anti-HBe; reactivation or reversion to HBeAg-positive status can occur.
GEOGRAPHIC DISTRIBUTION OF CHRONIC HBV INFECTION
The global prevalence of HBV varies widely. Regions are divided into areas of low, intermediate, and high prevalence, defined as follows4:
- High prevalence implies that at least 8% of the population is currently infected, with a lifetime likelihood of active or resolved infection greater than 60%. About 45% of the world’s population lives in regions of high prevalence. Among this group, early childhood infections are common, with the virus usually transmitted from mother to infant during the perinatal period.
- Intermediate prevalence is defined as 2% to 7%, with a lifetime risk of infection of 20% to 60%. These regions represent about 43% of the global population. In intermediate-prevalence areas, infections occur in all age groups.
- Low prevalence is defined as less than 2% and represents only 12% of the global population. In these regions, the lifetime risk of infection is less than 20%.
North America is a low-prevalence area except for the northern rim, where Inuit and Yupik Eskimos have a high prevalence, and communities that have a substantial immigrant population from high-prevalence areas, such as sub-Saharan Africa and many parts of Asia.
Chronic HBV infection in the United States
Approximately 1.25 million individuals in the United States are HBsAg carriers.2,4 In Asian Americans and Alaskan natives, the prevalence of HBsAg positivity, or chronic disease, is 5% to 15%.5,6 Similarly, US health statistics sources estimate that among those who are chronically infected, approximately half are Asian American.7 As the Asian American population continues to increase (1.5 million to 7 million from 1970 to 19905,8; 11.9 million in the 2000 US Census8), the total prevalence of chronic HBV infection will increase as well.