Phases of HBV infection are 1) immune-tolerant, 2) immune-active, 3) inactive chronic (inactive carrier), 4) immune-escape (HBeAg-negative chronic), and 5) reactivation. Alanine aminotransferase (ALT) and HBV DNA levels can be helpful in differentiating the phases of HBV infection:
- Immune-tolerant phase: ALT levels are normal; HBV DNA levels are high.
- Immune-active phase: ALT levels can be high or intermittently high; HBV DNA levels can fluctuate.
- Inactive chronic hepatitis (inactive carrier) phase: ALT levels are normal and HBV DNA levels are low or undetectable.
- Immune-escape phase (HBeAg-negative chronic hepatitis): ALT levels are elevated or may fluctuate; HBV levels tend to be moderate or high.
- Reactivation phase: ALT levels are elevated; HBV levels tend to be moderate or high.
However, because of the overlap in ALT and HBV DNA patterns between phases, these markers are not sufficient to identify the exact phase of disease.13 Analysis of multiple markers of HBV infection will be helpful in determining disease phase and potential treatment options. Quantitative HBsAg determination and HBeAg status may be additional markers that can be useful for prognosis and therapeutic decision-making in patients with different phases of infection. For example, HBeAg-negative patients with low HBV DNA (<2000 IU/mL), low HBsAg (<1000 IU/mL), and selected genotypes may be considered to be in the inactive carrier state.2 Low serum HBsAg levels measured 1 year after documented HBeAg seroconversion may predict subsequent HBsAg loss in genotype B or C infection.5 Conversely, lack of HBsAg decline and modest (<2 log) reduction in HBV DNA after the third month of antiviral treatment has been suggested as a stopping rule in HBeAg-negative patients with genotype D.6,7 Like HBV DNA levels, HBsAg and HBeAg levels are typically highest in the immune-tolerant phase, decline in the immune-active phase, and are generally lowest in the inactive carrier phase.