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Diagnostic tests to determine phase of acute or chronic hepatitis B virus infection[1]

Diagnostic tests to determine phase of acute or chronic hepatitis B virus infection[1]
HBsAg HBeAg IgM anti-HBc Total anti-HBc* Anti-HBs Anti-HBe HBV DNA ALT Interpretation
Acute HBV infection
+ + + ±     +++ Elevated Early phase
    + ±     + Elevated Window phase
      + + + ± Normal Recovery phase
Chronic HBV infection (HBsAg-positive for >6 months)
+ +   + - -

+++

(Serum HBV typically >1 million international units/mL)

Normal or mildly elevated Immune-tolerant phaseΔ
+ +   + - -

+++

(Serum HBV >20,000 international units/mL)

Persistently elevated Immune-active, HBeAg-positive
+ -   + - +

++

(Serum HBV >2000 international units/mL)

Elevated Immune-active, HBeAg-negative
+ -   +   +

- to ++

(Serum HBV ≤2000 international units/mL)

Normal or mildly elevated Inactive chronic HBV§
- -   ± (generally +) ±  ± + in liver; - to + in serum  Normal Occult HBV
ALT: alanine aminotransferase; anti-HBc: antibody to hepatitis B core antigen; anti-HBe: antibody to hepatitis B e antigen; anti-HBs: antibody to hepatitis B surface antigen; HBeAg: hepatitis B e antigen; HBsAg: hepatitis B surface antigen; HBV: hepatitis B virus.
* This test is typically ordered as total anti-HBc, which includes IgM and IgG.
¶ The upper limits of normal for ALT in healthy adults are reported to be 29 to 33 units/L for males and 19 to 25 units/L for females. For healthy children after infancy, the upper limits of normal are 25 to 38 units/L and 22 to 31 units/L for boys and girls, respectively.
Δ For patients with immune-tolerant chronic hepatitis B, liver biopsy or noninvasive tests show no fibrosis and minimal inflammation. This is the initial phase seen in patients with perinatally acquired HBV infection.
◊ For patients with immune active chronic hepatitis B, liver biopsy or noninvasive tests show chronic hepatitis with moderate or severe necroinflammation with or without fibrosis. For patients who are HBeAg positive, immune-active chronic hepatitis B (also known as the clearance phase) can last for 10 to 20 years, and may be associated with the loss of HBeAg. For patients who are HBeAg negative, immune-active chronic hepatitis B is associated with immune reactivation and is also referred to as HBeAg-negative chronic hepatitis B or HBeAg-negative replicative phase.
§ Patients with inactive chronic hepatitis B are HBeAg negative. In such patients, liver biopsy confirms the absence of significant necroinflammation, but biopsy or noninvasive testing show variable levels of fibrosis. This stage has also been referred to as the nonreplicative or carrier phase.
References:
  1. ​Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018; 67:1560.
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