People acutely infected with hepatitis B virus (HBV) may be asymptomatic or symptomatic. The likelihood of developing symptoms of acute hepatitis is age dependent: less than 1% of infants younger than 1 year of age, 5% to 15% of children 1 to 5 years of age, and 30% to 50% of people older than 5 years of age are symptomatic. Among people with symptomatic HBV infection, the spectrum of signs and symptoms is varied and includes subacute illness with nonspecific symptoms (eg, anorexia, nausea, or malaise), clinical hepatitis with jaundice, or fulminant hepatitis. Extrahepatic manifestations, such as arthralgia, arthritis, macular rashes, thrombocytopenia, or papular acrodermatitis (Gianotti-Crosti syndrome), can occur early in the course of the illness and may precede jaundice. Acute HBV infection cannot be distinguished from other forms of acute viral hepatitis on the basis of clinical signs and symptoms or nonspecific laboratory findings.

Chronic HBV infection is defined as presence of hepatitis B surface antigen (HBsAg) in serum for at least 6 months or by the presence of HBsAg in a person who tests negative for antibody of the immunoglobulin (Ig) M subclass to hepatitis B core antigen (IgM anti-HBc).

Age at the time of acute infection is the primary determinant of the risk of progressing to chronic infection. More than 90% of infants infected perinatally will develop chronic HBV infection. Between 25% and 50% of children infected between 1 and 5 years of age become chronically infected, whereas only 2% to 6% of acutely infected older children and adults develop chronic HBV infections. Patients who develop acute HBV infection while immunosuppressed or with an underlying chronic illness have an increased risk of developing chronic infection. In the absence of Treatment, up to 25% of infants and children who acquire chronic HBV infection will die prematurely from HBV-related hepatocellular carcinoma or cirrhosis.

The clinical course of untreated chronic HBV infection varies according to the population studied, reflecting differences in the age at acquisition, the rate of loss of hepatitis B e antigen (HBeAg), and possibly, HBV genotype. Perinatally infected children usually have normal alanine transaminase (ALT) concentrations and minimal or mild liver histologic abnormalities for years to decades after initial infection ("immune tolerant phase"). Chronic HBV infection acquired during later childhood or adolescence usually is accompanied by more active liver disease and increased serum transaminase concentrations. Patients with detectable HBeAg (HBeAg-positive chronic hepatitis B) usually have high concentrations of HBV DNA and HBsAg in serum and are more likely to transmit infection. Because HBV-associated liver injury is thought to be immune-mediated, in people coinfected with human immunodeficiency virus (HIV) and HBV, the return of immune competence with antiretroviral Treatment of HIV infection may lead to a reactivation of HBV-related liver inflammation and damage. Over time (years to decades), HBeAg becomes undetectable in many chronically infected people. This transition often is accompanied by development of antibody to HBeAg (anti-HBe) and decreases in serum HBV DNA and serum transaminase concentrations and may be preceded by a temporary exacerbation of liver disease. These patients have inactive chronic infection but still may have exacerbations of hepatitis. Serologic reversion (reappearance of HBeAg) is more common if loss of HBeAg is not accompanied by development of anti-HBe; reversion with loss of anti-HBe also can occur.

Some patients who lose HBeAg may continue to have ongoing histologic evidence of liver damage and moderate to high concentrations of HBV DNA (HBeAg-negative chronic hepatitis B) . Patients with histologic evidence of chronic HBV infection, regardless of HBeAg status, remain at higher risk of death attributable to liver failure compared with HBV-infected people with no histologic evidence of liver inflammation and fibrosis. Other factors that may influence natural history of chronic infection include gender, race, alcohol use, and coinfection with hepatitis C or hepatitis D viruses.

Resolved hepatitis B is defined as clearance of HBsAg, normalization of serum transaminase concentrations, and development of antibody to HBsAg (anti-HBs). Chronically infected adults clear HBsAg and develop anti-HBs at the rate of 1% to 2% annually; during childhood, the annual clearance rate is less than 1%. Reactivation of resolved chronic infection is possible if these patients become immunosuppressed.