Viral hepatitis B: clinical and epidemiological characteristics

Abstract

It is now 50 years since the discovery of the hepatitis B virus (HBV), and, despite the availability of a prophylactic vaccine for more than 20 years, HBV infection remains a disease of significant global health burden. It is estimated that more than 240 million people are chronically infected with HBV and, therefore, are at risk for the development of cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). The risk of clinical complications has traditionally been higher in older males with hepatitis B e antigen (HBeAg)-positive disease, high-grade liver necroinflammation, and progressive fibrosis. Recent advances in the understanding of the natural history of chronic HBV infection have identified an important role for plasma HBV DNA levels as a marker of risk for clinical outcomes. Among adults, persistent high-level HBV replication is associated with an increased risk of cirrhosis, as well as HCC development. This has led to the therapeutic focus on achieving sustained viral suppression. There is an emerging role for quantitative hepatitis B surface antigen (HBsAg) levels as a marker of natural history. Low levels of HBsAg have been associated with sustained immune control, HBsAg seroclearance, as well as lower risk of HCC. In this work, we review the natural history of HBV infection, with a focus on the determinants of clinical outcomes in patients with chronic hepatitis B (CHB) infection.

Figure 1.

The natural history of CHB, showing relationships between serology, biochemistry, and molecular virology. (Figure created from data in Lok and McMahon 2007.)

Figure 2.

Distribution of serum HBsAg titres throughout the natural history of CHB. IT, immune tolerant; IC, immune clearance; LR, low replicative; ENH, HBeAg-negative hepatitis. (From Nguyen et al. 2010; reprinted, with permission, from Elsevier © 2010.)