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My name is Fernando Florido (also known as Juan Fernando Florido Santana) and I am a General Practitioner in the United Kingdom. In this episode I go through a variety of guidelines and publications on hepatitis B serology in order to clarify the concept and understand the interpretation of the results. You can find links to the resources consulted in the description below.  

I am not giving medical advice; this video is intended for health care professionals, it is only my summary and my interpretation of the guidelines and you must use your clinical judgement.   

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The links to the guidance covered in this episode can be found here: 

NICE guideline on hepatitis B:  

https://www.nice.org.uk/guidance/cg165/chapter/Recommendations#assessment-and-referral-in-primary-care 

Hepatitis B Foundation:  

https://www.hepb.org/prevention-and-diagnosis/diagnosis/understanding-your-test-results/

BMJ article:  

https://www.bmj.com/bmj/section-pdf/756691?path=/bmj/348/7957/Practice.full.pdf 

Hepatitis B online guidance for Primary Care (PDF):

https://www.hepatitisb.uw.edu/page/primary-care-workgroup/guidance

Hepatitis B online module:  

https://www.hepatitisb.uw.edu/go/screening-diagnosis/diagnosis-hbv/core-concept/all 

GP notebook:

https://gpnotebook.com/en-GB/pages/trauma-medicine/hepatitis-b-serology-summary 

NICE guidance:  

https://www.nice.org.uk/guidance/ph43/chapter/Recommendations#recommendation-4-testing-for-hepatitis-b-and-c-in-primary-care 

WHO hepatitis recommendations (PDF):  

https://iris.who.int/bitstream/handle/10665/254621/9789241549981-eng.pdf 

Public Health England:  

https://www.gov.uk/government/publications/infectious-diseases-in-pregnancy-screening-programme-laboratory-handbook/results-table-and-reporting-comments-for-hepatitis-b

Disclaimer:

 The Video Content on this channel is for educational purposes and not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read or seen on this YouTube channel. The statements made throughout this video are not to be used or relied on to diagnose, treat, cure or prevent health conditions.

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Transcript

If you are listening to this podcast on YouTube, for a better experience, switch to the video version. The link is in the top right corner of the video and in the episode description.

Hello and welcome, I am Fernando, a GP in the UK. Today, we will go through the interpretation of hepatitis B serology. For this, I have consulted a variety of guidelines and publications in order to clarify the concepts. You can find links to the resources consulted in the episode description. 

Right, let’s jump into it. 

To interpret hepatitis B serology, first we have to understand the viral antigens and then their corresponding antibodies. So, let’s break them down one by one.

Let’s look at the antigens first. There are three antigens in the hepatitis B virus. 

The Hepatitis B Surface Antigen is found on, well, the surface of the hepatitis B virus. This antigen is produced during active viral replication and indicates the presence of infection, appearing in the blood both during acute and chronic infections.

Then we have the Hepatitis B e Antigen, which is found between the core and the viral membrane and it is released into the bloodstream during the replication of the virus.

And then, the third antigen is the Hepatitis B Core Antigen, which is located within the nucleus of the virus and is not directly detectable in the blood. So, it plays no part in the serology testing but it is important because of the antibodies that it can produce.  

So, let us look at the antibodies now. We have three antigens, so we also have three antibodies,  

The surface antibodies

The e antibodies and

The core antibodies. 

So let us have a look at the clinical implications of both antigens and antibodies.  

As we said earlier, the hepatitis B surface antigen is the main marker of hepatitis B infection. So, a negative result means that there is no active infection. This could be because the person has never been infected or because the infection has cleared.

On the other hand, a Positive result confirms an active infection (either acute or chronic). In an acute Infection, the surface antigen is detectable 1-10 weeks after exposure, with an average of one month, and it generally clears within 6 months if the infection resolves. However, if the surface antigen persists for more than 6 months, it indicates chronic hepatitis B.

It may be worthwhile mentioning that during Hepatitis B vaccination, the person is injected with surface antigen and, as a result, after receiving the vaccine, this antigen can sometimes be briefly detected in the blood, usually within 14 days post-vaccination and does not persist beyond this period. In this case, this transient positivity is not indicative of an actual infection but it is rather connected to the administration of the vaccine.

And what about the hepatitis B surface antibody?

Well, the surface antibody is produced by the immune system and if it is positive, then this usually indicates that the person has developed immunity either by:

·      Successfully clearing a previous Hepatitis B infection or by

·      Being successfully vaccinated.

Therefore, the surface antibodies, provide immunity against future infections and neutralise the surface antigen. Consequently, it is not possible to test positive for both surface antigen and surface antibodies at the same time. 

On the other hand, a negative surface antibody indicates that the person has no immunity to the hepatitis B virus and is susceptible to infection. 

Next, let’s look at the e Antigen. It is associated with viral replication and:

·      In an acute Infection, it appears shortly after the surface antigen during the acute phase, indicating active viral replication and

·      In chronic hepatitis B, its presence also suggests high levels of viral replication and infectivity. However, some patients transition to an e antigen-negative chronic phase due to viral mutations.

So, in summary:

·      A Positive e antigen test indicates a high viral load, high infectivity, and it is often seen in acute infections or poorly controlled chronic infections.

·      A Negative result may indicate lower replication or mutant forms of the virus that do not produce the e antigen.

What about the e antibodies? Well, e antibodies are also produced as the immune system suppresses viral replication. So, if the e antibodies are positive, then this usually indicates a suppressed low viral replication and reduced infectivity, whereas a negative result suggests active viral replication in an infected person. 

Finally, let’s look at the core antigen and core antibodies.

As explained, earlier, the core antigen is not detectable in the blood, so, it plays no part in the serology. On the other hand, the core antibodies have got much more clinical significance because they work as key markers of infection history.  

There are two types of core antibodies:

• IgM antibodies, which indicate recent or acute infection and remains detectable during the acute phase only, becoming negative in chronic or resolved infection. And then we have
• IgG antibodies, which suggest previous exposure to the hepatitis B virus and these IgG antibodies persist for life as a marker of past infection.

Please note one difference between the surface antibodies and the core antibodies. The surface antibodies confer immunity whereas the core antibodies do not. So, a positive surface antibody means that there is no active disease, whereas positive Ig G core antibodies may suggest either a previous resolved infection, or also active chronic disease. 

So how do we interpret hepatitis B serology results?  

Well, Most path labs will use the 3-part “Hepatitis B Panel”, testing for: 

·      The surface antigen to check for active infection

·      The surface antibody to check for immunity

·      And the core antibody to check for past or current infection.

·      Additionally, and in certain circumstances, generally when some of the previous tests are positive, the path lab will test for the e antigen and the e antibodies. This is to check for levels of viral replication and infectivity.

Right, to finalise, let’s look at common scenarios: 

1.   A:

·      Negative surface antigen

·      A Negative surface antibody and

·      A negative core antibody

Would correspond to someone who has not been infected and who is not immune and therefore not protected, so these people should be advised vaccination if at risk of infection. 

2.   A:

·      Negative surface antigen

·      A positive surface antibody and

·      A positive core antibody

Would correspond to someone who has been infected but has successfully cleared the infection. These people are immune and do not need vaccination. 

3.   A:

·      Negative surface antigen

·      A positive surface antibody and

·      A negative core antibody

Would correspond to someone who has never been infected but that has been successfully vaccinated. 

4.   A:

·      Positive surface antigen

·      A Negative surface antibody and

·      A positive core antibody

Would correspond to someone who has been infected. These people should have more testing, for example, to determine IgM and IgG core antibodies and possible e antigen and e antibodies 

5.   A:

·      Positive surface antigen

·      A negative surface antibody

·      A Positive IgM core antibody

·      A Positive e antigen

Would correspond to someone with an acute hepatitis B infection with high levels of viral replication and infectivity.

6.   A:

• Positive surface antigen (for more than 6 months)
• A negative surface antibody
• A Positive total core antibody
• A Negative IgM core antibody and
• A Positive or Negative e antigen

Would correspond to someone with a chronic Infection, with the e antigen simply determining whether the person is highly infectious because of high viral replication or not.

7.   A:

• Negative surface antigen
• A negative surface antibody and
• A Positive IgM core antibody

Would correspond to someone in a Window Period. The surface antigen is negative in the window period because it has been cleared from the bloodstream by the immune system, which has not yet produced enough surface antibodies to be detected. In this case, the presence of positive IgM core antibody is crucial for the diagnosis during this transitional phase.

And finally

8.   A:

·      Negative surface antigen

·      A negative surface antibody and

·      A Positive IgG core antibody

Is probably the trickiest scenario. An isolated positive IgG core antibody, that is, with a negative surface antigen and a negative surface antibody, has 4 possible causes:

1) It may be the "window phase" between disappearance of the surface antigen and appearance of surface antibodies

2) It may represent a remote resolved infection with the decline of surface antibodies to undetectable levels

3) It could also indicate ongoing chronic infection with low levels of surface antigen which are undetectable, or

4) It may represent a false-positive test (rare)

So that is it, a review of hepatitis serology and its interpretation.

We have come to the end of this episode. Remember that this is not medical advice but only my summary and my interpretation of the guidelines. You must always use your clinical judgement.

Thank you for listening and goodbye.