The prevalence and natural history of hepatitis B in the 21st century

Author and Disclosure Information


The prevalence of chronic hepatitis B virus (HBV) infection varies by geographic region. Most of North America is a low-prevalence (< 2%) area. Certain high-prevalence pockets exist, especially areas with a high proportion of Asian immigrants and Alaskan and northern Canadian native populations, where rates of chronic HBV are as high as 5% to 15%. In most low-prevalence areas, HBV infection is acquired mainly during adolescence and midadulthood, whereas perinatal transmission is the main route in high-prevalence (≥ 8%) areas. Up to 40% of patients with chronic HBV infection develop liver complications. Age at acquisition affects the likelihood of chronicity and the development of liver complications. The risk of each is greatest with perinatal transmission; the disease is usually self-limiting when exposure to HBV occurs during adolescence or young adulthood. Viral load predicts progression to cirrhosis and hepatocellular carcinoma; therefore, reducing viral load is the major goal of treatment.


  • The prevalence of chronic HBV infection in the United States is expected to increase as Asian immigrants constitute a larger proportion of the US population.
  • The chance of chronic infection is 90% or greater with perinatal transmission; conversely, the risk of chronic disease is less than 10% with adult-acquired infection.
  • In addition to viral load, predictors of disease progression include age at onset, male sex, and comorbidities.



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.


Familiarity with the terms commonly used to describe chronic HBV infection will help clinicians in the management of the disease 4:

  • 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.


The global prevalence of HBV varies widely. Regions are divided into areas of low, intermediate, and high prevalence, defined as follows 4:

  • 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%.

Next Article:

Risk of hepatocellular carcinoma in hepatitis B and prevention through treatment

Related Articles