E antigen positive for decades despite the antiviral

Are there updated articles on situation with e antigen positive for a long duration despite on antiviral meds? I supposed this maybe an unusual case.

The end point of antiviral therapy is to seroconvert to e antigen negative, at least this was the goal several years back.

What is the protocol and aim for antiviral therapy today?

What is the prospect on a patient who fails to seroconvert to e antigen positive?

thank you!

Dear @catcher.007 ,

The goal and endpoint of currently approved antiviral therapies is the suppression of viral replication (measured by the HBV DNA test), the normalization of liver function (measured primarily by the ALT test) and halting the progression of liver disease (fibrosis and cirrhosis).

HBeAg elimination and anti-HBe seroconversion do occur in many patients but this event does not measure control of viral infection or an ability to safely remove treatment (this is a function of HBsAg clearance).

In patients who do seroconvert for HBeAg, HBsAg loss is very rare so in principle, there is very little difference between long term outlook between HBeAg negative and HBeAg positive patients with effective suppression of viral replication who remain HBsAg positive.

Best regards,

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Thank you for your response.

A loss of surface antigen is so rare, I’m not expecting that to occur.
I was concerned that as one ages and the immune system becomes weaker, if the e antigen remains negative despite the antiviral therapy, it could potentially result in a bad outcome in a liver.

e antigen positive at least means, the virus is not replicating.

does e antigen negative mean, it could be an aggressive kind of hbv ? if that makes any sense.

thank you!

Dear @catcher.007 ,

Lets clarify this issue a bit to help you…

HBeAg is not a part of the virus and is produced in and secreted from infected cells independently from the production of virus. It is a not a marker of viral replication.

The transition from HBeAg positive to HBeAg negative during the natural history or treatment of chronic HBV infection is a complicated issue: its absence can signal the presence of some immune control in the patient or can signal the presence of mutations blocking the production of HBeAg. Curiously, the disappearance of HBeAg makes the antiviral response to immunotherapy weaker.

So the appearance of antibodies to HBeAg does not really have any meaningful diagnostic impact on liver disease (but has been linked to the response to immunotherapies as discussed above). In the rare cases of HBsAg loss, these patients always become HBeAg negative and HBeAb positive prior to this event.

In most cases, HBeAg positivity indicates an earlier stage of chronic infection where viral replication is higher.

In the context of oral antiviral therapy, the HBeAg issue is irrelevant to the control of the virus long term and to the ability of these therapies to control liver disease.

Best regards,

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Hi @availlant

Thanks for the insight. I wanted to know is HbeAG negativity in precore and BCP mutation reason to be concerned? I got this mutant HBV where it doesnt produce HbeAg. I am not on medication but my viral load is in a decreasing trend came down from 16100IU in nov to 5500IU in Feb and in May came down to 3270iu. What does this mean? My HbsAG was above >25000IU in results. Please advice

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Hi @Ash_Malhotra,

These sorts of mutations happen over the course of an infection. Some studies have shown they occur even in early stages of infection and are linked to quicker HBeAg seroconversion (https://aasldpubs.onlinelibrary.wiley.com/doi/abs/10.1002/hep.31506). There are some studies finding a correlation with disease progression, but it’s not clear whether it’s just because people who have lower HBV DNA (when mutations cannot be detected) have lower disease progression. As far as I am aware, these don’t really have an impact on how you are treated.

Thomas

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my response had an error.
I meant to say that if the e antigen remains positive (not negative) despite the antiviral therapy, is it an aggressive kind?

Hi @catcher.007,

As @availlant mentioned, HBeAg isn’t affected by antivirals such as entecavir or tenofovir. You wouldn’t expect it to change on treatment, the most important thing to see if it’s working is reduction of HBV DNA. Remaining HBeAg positive does not indicate it is aggressive.

Thomas

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