REVIEWNatural History of Hepatitis B Virus Infection: An Update for Clinicians
Section snippets
PATHOGENESIS OF HBV INFECTION
The observation that many HBV carriers are asymptomatic with minimal liver injury, despite extensive and continuing intrahepatic replication of the virus, supports the concept that HBV is not directly cytotoxic to hepatocytes.8, 9 The severity of hepatocellular injury is modulated by the strength of host immune responses.10, 11, 12 In patients with fulminant HBV infection, rapid viral clearance is achieved after severe liver injury as a result of a vigorous host immune response.10, 11, 12
ACUTE HBV INFECTION
In acute HBV infection, hepatitis B surface antigen (HBsAg) becomes detectable in the serum after an incubation period of 4 to 10 weeks, followed shortly by the appearance of antibody against the hepatitis B core antigen, which is predominantly of the IgM isotope in the early phase.23 Levels of HBV DNA are generally very high, frequently in the range of 200 million IU/mL to 200 billion IU/mL (109–1012 copies/mL).24 Circulating HBeAg can be detected in most patients with acute HBV infection, and
PHASES OF CHRONIC HBV INFECTION
Those with chronic HBV infection may present: (1) in a state of immune tolerance, (2) with HBeAg-positive chronic hepatitis, (3) as an inactive HBsAg carrier, or (4) with HBeAg-negative chronic hepatitis (Figure 1).
Chronic HBV Infection and Cirrhosis
Sequelae of chronic HBV infection may include mild to moderate fibrosis, compensated cirrhosis, hepatic decompensation, and HCC. The annual incidence of cirrhosis in patients with HBeAg-negative chronic hepatitis may be as high as 8% to 10%, compared with 2% to 5% in those with HBeAg-positive chronic hepatitis.62, 94, 95, 96 The higher rate of cirrhosis in patients presenting with HBeAg-negative chronic hepatitis, a late phase in the natural history of chronic HBV infection, is not surprising
SUMMARY AND CONCLUSIONS
The dynamic balance between viral replication and host immune response plays a key role in the pathogenesis of liver disease from HBV infection. Most infections in immunocompetent adults are resolved, whereas most neonates and infants develop chronic HBV infection. Those with chronic HBV infection may present in 1 of 4 phases: (1) in a state of immune tolerance, (2) with HBeAg-positive chronic hepatitis, (3) as an inactive HBsAg carrier, or (4) with HBeAg-negative chronic hepatitis. Of these,
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This work was supported by grant DK 61617 from the National Institute of Diabetes and Digestive and Kidney Diseases.