Hepatitis B “Two Pairs and a Half” is a routine test for hospital admission. I hadn’t fully understood it for a long time, so I studied it again and found that understanding the structure of the hepatitis B virus and the immune process is essential to comprehend these indicators (my notes only covered the structure, not the immune process; for more details, please refer to other references).
As always, English is very important. The structure of the hepatitis B virus is already embedded in its English name. For example, the Chinese term “乙肝e抗原” refers to the hepatitis B e antigen. What is the e antigen? Why isn’t it a, b, c, or d antigen?
It turns out “e” means escape. The e antigen is located between the surface antigen and the core antigen, and during viral replication, it escapes into the extracellular space.
Main Text
Antigen
Description
Antibody
Description
[[Hepatitis B surface antigen]] (HBsAg), located on the virus surface, can be detected in the blood
Infection marker; positive means past infection, current infection, or vaccination (vaccines contain antigen to stimulate antibody production)
[[Hepatitis B surface antibody]] (HBsAb)
Protective antibody; positive means past infection, current infection, or vaccination (vaccines contain antibodies to directly neutralize the virus)
[[Hepatitis B e antigen]] / Hepatitis B escape antigen (HBeAg), located between surface antigen and core antigen, secreted into the blood during viral replication
Marker of active replication; positive indicates active viral replication; strong positive in acute phase temporarily; persistent positivity indicates chronic phase; seroconversion indicates virus no longer replicating
[[Hepatitis B e antibody]] (HBeAb)
Marker of low replication; positive indicates viral replication has passed peak and is still in immune response phase, mostly during acute hepatitis recovery
Hepatitis B core antigen (HBcAg), located in the virus core, generally not detectable in blood
Usually undetectable
[[Hepatitis B core antibody]] (HBcAb)
Positive indicates past or current infection
“Big Three Positives” and “Small Three Positives” both reflect states of hepatitis B virus carriage in the body and are two different results of the hepatitis B “two pairs and a half” test.
Neither hepatitis B “Big Three Positives” nor “Small Three Positives” indicate whether liver function is normal; liver function tests and hepatitis B DNA must be combined for evaluation.
About Hepatitis B Virus DNA
A few days ago, I heard a report mentioning that DNA is currently the new gold standard, more accurate than the hepatitis B two pairs and a half test. It is also gradually becoming popular in clinical practice (thanks to @吴子彧 for the supplement https://forum.beginner.center/t/topic/613/3).
A simple explanation first: This test is very important for hepatitis B patients. In addition to the two pairs and a half (serological markers) and liver function tests, DNA testing is indispensable. Dongzhimen Hospital can perform this test, and it is relatively common. Below is some guideline content to help everyone understand its significance simply.
The infectivity level of HBV-infected individuals mainly depends on the HBV DNA level in the blood and is unrelated to ALT/AST/bilirubin levels. That is, even people with normal liver function may have viral replication and be HBV DNA positive.
HBV DNA > 2,000 IU/ml is one of the risk factors for untreated chronic hepatitis B patients progressing to liver cirrhosis.
Guideline recommendation (A1): For HBsAg-positive individuals, including CHB patients receiving antiviral treatment, high-sensitivity HBV DNA detection methods with a wide linear range (quantification lower limit of 10–20 IU/ml) should be used whenever possible.
Guideline recommendation (B1): For those with serum HBV DNA positivity, persistent abnormal ALT (>ULN), and after excluding other causes, antiviral treatment is recommended (B1).
Guideline recommendation: For serum HBV DNA-positive individuals, regardless of ALT level, antiviral treatment is recommended if any of the following conditions are met: (1) family history of hepatitis B-related liver cirrhosis or HCC (B1); (2) age > 30 years (B1); (3) non-invasive indicators or liver histology showing significant liver inflammation (G≥2) or fibrosis (F≥2) (B1); (4) HBV-related extrahepatic manifestations (such as HBV-related glomerulonephritis) (B1).
Antiviral treatment: For HBeAg-positive chronic hepatitis B patients, once HBV DNA is undetectable and seroconversion of HBeAg occurs, if HBsAg is less than 100 IU/ml, the risk of relapse after stopping treatment can be reduced.
For HBeAg-negative chronic hepatitis B patients, generally, longer-term treatment is needed. Antiviral discontinuation can be considered only after HBV DNA is undetectable, HBsAg disappears and/or anti-HBs appears, and at least 6 months of consolidation therapy have been completed.
The above content is sourced from the guidelines. For detailed content, please refer to the guidelines.
Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association. Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Edition) [J]. Infectious Disease Information, 2023, 36(1):1-17. DOI:10.3969/j.issn.1007-8134.2023.01.01.
