Early Viral Suppression - HCC

I wanted to ask a question and hoping the experts can weigh in.

I recently met with my doctor asking to go on antivirals , largely due in part to what I was reading here about studies showing that starting anti virals early can reduce integration into host DNA, even if you’re an inactive carrier. The part I distinctly remember and recalled to my doctor was a study @availlant cited (POLARIS?) that starting antivirals before age 50 showed reduced rates of HCC and starting antivirals after age 50 did not reduce these rates. (Can someone link me to this so I can send my doctor. - thanks!)

Anyway, my doctor was on board and agreed to put me on antivirals after my next round of blood tests.

However I came along this article

That is saying long term prognosis for HCC is better if you’re not on treatment?

My latest viral load showed <10iu/ml Altho I believe I recently must have had a mutant virus escape because a few years ago my viral load showed 2000iu/ml and then quickly went back down and surface antibodies showed up (100iu/ml) but I still have chronic hbv as my HSBAG was 20,000.

All this to say,

Do I bother going on them with such a low viral load and seemingly no raise in ALT/AST (12iu/ml). I’m 35 Female. I know this more of a question for my doctor but just wondering any additional thoughts I can bring up to him because he is open minded to any studies I send him and will review them with me.

Thanks for your thoughts :slight_smile:

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Dear @Albasil808 ,

One of the first studies to show the benefit of starting NUCs early is here.

However, while early adoption of NUC therapy can lower the risk of HCC, it does not abolish it. The paper you cite is a very small study of 5 patients showing the development of HCC with NUC suppression. You should not infer the overall risk of HCC with NUC suppression from this paper - it is known to be less than when not taking NUCs.

While HBV DNA integration occurs in all patients with chronic HBV infection, the rate of integration events is considered to be related to the activity of viral replication. So integration rate is high when viral load is above 20,000 IU/mL and low when below 2,000 IU/mL. HCC risk is commensurate with this.

So is important to understand that in your case, your viral load is very low (you have partial cure - normal ALT - even with the high HBsAg) - so we know in these situations that HCC risk is lower even than people requiring NUC therapy (even when they start therapy early).

Introducing NUC therapy will not be dangerous but it will not have any appreciable impact on your HCC risk.

@availlant

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Hello, Dr. @availlant

My case is a little different from @Albasil808. The virus I have is a pre-core mutant but my HBV DNA is 8.000 IU/ml. It is neither too low (>2.000) nor too high (<20.000). What would you advise me in my case?

I saw my hepatologist this week and insisted on taking medication. However, he is still waiting for an increase in ALT/AST or fibrosis 2, as prescribed in my country, Brazil. I am seriously considering taking this issue to court, since treatment for hepatitis B is only provided through public health.

Another question: does having a pre-core mutant influence the possibility of developing HCC? And is rep-2139mg being administered to patients with this type of mutant virus?

Dear @La.sciamachie,

Your doctor is following guidelines in place in most countries. It may be that the government does not pay for the medication outside of the these guidelines. This may be due to financial constraints.

If your HBV DNA were > 20,000 IU/mL, you would be eligible for therapy regardless of your liver status.

This idea of treating patients with normal liver function who have lower levels of HBV DNA is a relatively new and controversial one. Your integration rate will be on the low end but your desire to start therapy is still understandable given the cumulative effects of integration over time.

You might try finding another doctor who will prescribe you generic ETV or TDF outside of government insurance.

Having a pre-core mutant does not influence the chance of developing HCC. Although we have not given REP 2139-Mg to a patient we could prove had a pre-core mutant, this will have no impact on the activity of the drug since it targets the assembly and release of subviral particles. This process is unaltered in pre-core mutant virus.

@availlant

@availlant

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Thanks for your explanations, dr. @availlant