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Hepatitis B: New Strategies for Diagnosis, Monitoring and Referral

Chronic hepatitis B (CHB) infection is a global public health issue. It is estimated that 400 million people are infected worldwide and that it is associated with 500,000–700,000 deaths per year. While approximately 75% of infected individuals reside in Asia, other areas of endemicity include Africa, and Southern and Eastern Europe. However, even in areas with low prevalence there exist sub-groups in whom the infection rate is far higher than in the general population.

Epidemiology in Canada

In Canada, it is estimated that approximately 600,000 individuals have CHB infection. While the overall prevalence of infection in the general population is low, there are sub-populations with higher prevalence rates, particularly immigrant groups, the Inuit population, and intravenous drug users. Furthermore, the overall number of individuals with CHB infection is increasing because of immigration from endemic areas e.g., South-East Asia, including China, Korea and Vietnam, and Southern and Eastern Europe (1).Figure 1

Natural history of chronic hepatitis B infection

Our understanding of the natural history of CHB infection has evolved significantly over the past decade (2). It is now recognised that CHB infection follows a dynamic course which varies between individuals. Although four phases have been identified, these do not necessarily follow a linear course and patients may switch between stages at any time. Furthermore, treatment is not warranted at every stage and it is therefore important to undertake regular monitoring of patients with HBV infection to identify their current disease stage and to thereby determine whether they require treatment. Click here for further information on the stages of chronic HBV infection.

Figure 2The immune tolerant phase can last for many years, particularly in those infected in the perinatal period or during childhood. During this stage the immune system fails to recognize the presence of HBV and therefore does not mount a response against the infected cells. This phase is characterised by high serum HBV DNA levels but normal ALT levels, with minimal hepatic inflammation and fibrosis on biopsy.

During the immune active stage, a high viral load (HBV DNA level) elicits an immune response leading to destruction of the infected hepatocytes. This leads to elevated serum ALT levels and inflammation and fibrosis on biopsy. This stage is often cyclical, leading to periods of inflammation and repair. Treatment is warranted during this phase with the aim of reducing viral load, and promoting seroconversion from hepatitis B e antigen (HBeAg-) positive to hepatitis B e antibody (anti-HBe-) positive state.

Table 1In the inactive carrier phase, seroconversion to anti-HBe has occurred, either spontaneously or treatment induced. HBV DNA levels fall to low or undetectable levels and serum ALT is persistently normal. This stage is associated with disease quiescence and fibrosis does not progress. However, patients remain at risk of hepatocellular carcinoma, particularly those with pre-existing cirrhosis. Furthermore, disease reactivation may occur and regular monitoring should continue.

Patients in the inactive carrier phase are not "cured", as HBV is never fully eradicated. Disease reactivation may occur during periods of immunosuppression and some individuals may develop HBeAg-negative disease. This occurs as a result of mutations in the precore or core promoter region of the HBV which enable the virus to escape the host’s immune response. Consequently, despite the absence of HBeAg and the presence of anti-HBe (similar to the inactive phase), the viral load (HBV DNA level) rises and inflammation and fibrosis occur. In patients with HBeAg-negative disease the serum HBV DNA level is often lower than in those in the immune active phase. (3)