Interpretation of hepatitis serology

What it is

Hepatitis B serology is read from three tests taken together: HBsAg, anti-HBs and anti-HBc. When anti-HBc is read as IgM or IgG, and HBeAg, anti-HBe and HBV DNA are added, the same three tests give a wider picture that also separates the phases of chronic infection. Chronic hepatitis B infection is defined as persistent detection of HBsAg for more than 6 months after initial exposure to the virus.

How it is diagnosed

Read together, the results run like this.

• Susceptible and non-immune: HBsAg negative, anti-HBc negative, anti-HBs negative.
• Acutely infected: HBsAg positive, anti-HBc positive with IgM anti-HBc positive, anti-HBs negative.
• Chronically infected: HBsAg positive, anti-HBc positive with IgM anti-HBc negative, anti-HBs negative.
• Immune due to natural infection: HBsAg negative, anti-HBc positive as IgG, anti-HBs positive.
• Immune due to hepatitis B vaccination: HBsAg negative, anti-HBc negative, anti-HBs positive.
• Anti-HBc positive alone, with HBsAg and anti-HBs both negative: the interpretation is unclear, with four possibilities, which are resolved infection and this is the most common, a false-positive anti-HBc so the patient is susceptible, low level chronic infection with an HBsAg too low to detect, and resolving acute infection where anti-HBs has not developed yet.

Adding the rest of the panel separates the chronic phases. Acute hepatitis B, and occasionally reactivation of chronic hepatitis B, gives HBsAg positive, IgM anti-HBc positive, HBeAg positive and HBV DNA above 20,000. Resolved previous infection gives anti-HBs and IgG anti-HBc positive with undetected DNA, and immunity from previous vaccination gives anti-HBs alone with undetected DNA. The chronic hepatitis B inactive carrier state gives HBsAg and IgG anti-HBc positive with anti-HBe positive and DNA under 20,000. HBeAg-positive chronic hepatitis B gives HBeAg positive with DNA above 20,000, and HBeAg-negative chronic hepatitis B gives anti-HBe positive with DNA above 10,000. That same source gives two HBV DNA numbers for HBeAg-negative chronic hepatitis B: above 10,000 U/mL where the results are interpreted, and at least 2,000 U/L where treatment is recommended. Both stand as written there, and neither is preferred over the other.

A fifth possibility is named for that same anti-HBc positive alone pattern: the person may be distantly immune, with a test not sensitive enough to detect a very low level of anti-HBs in serum.

Three worked cases show how the pattern is used:

• HBsAg positive with anti-HB core IgM positive, in a man with jaundice, tender hepatomegaly and ALT 900 and AST 900 against a normal below 40, is acute hepatitis B infection.
• HBsAg positive with HBcAb IgG positive and HBeAg positive, and anti-HBs negative, in a woman with jaundice and elevated liver enzymes, is chronic hepatitis B infection.
• HBsAb positive with anti-HBc IgG positive, and HBeAg and HBsAg both negative, is previous infection, not vaccination and not acute or chronic infection.