Taking Entecavir for 4 years, doctor wants me to start Peg-Inf 2b, should I?

[Tonyaod]

Medical History
=================
Vertical transmission, carrier since birth.
First flare up at age 40 in May of 2017 which was unrecognized as a flare up until jaundice developed.
Checked into the hospital for treatment, AST, ALT, TBIL all off the charts, HBV DNA values were high (the initial diagnosis blood work results were lost so don't have the actual values).
Doctor put me on entecavir .5 mg/day and other treatments for liver damage.

During the course of treatment the values were:
2017 June HBV DNA 6.025E+02 IU/ml, HBsAg-QN 1060
2017 July HBV DNA 2.608E+02 IU/ml
2017 Aug HBV DNA 1.204E+02 IU/ml, HBsAg-QN 1831
2017 Nov HBV DNA Undetectible, HBsAg-QN 2709
2019 May HBV DNA Undetectible, HBsAg-QN 2354
2021 May HBV DNA Undetectible, HBsAg-QN 1373

AST, ALT have remained in the mid-20s since the treatment.

Any suggestions or advice? Much appreciated!

[StephenCastlecrag]

I am not a doctor. It is not clear when you had your first flare whether you were HBeAg positive or negative. In my opinion, you should wait before starting  Interferon (Add-on or monotherapy?), my main reason is that your serum HBsAg is too high at the moment and any Interferon treatment will not be successful, and also you must consider the fairly serious potential side-effects. With Interferon treatment, you may lose HbsAg or become inactive after stopping treatment, but the success rates are low, below 30%. Before considering Interferon, you must consider:
1. Do you have cirrhosis(if, yes, Interferon should not be attempted);
2. Is your doctor experienced in Interferon treatment, he/she must be able to monitor your treatment and know when to stop;
3. What is your HBV genotype? (If type A, Interferon should be considered)

[Tonyaod]

Hi Stephan, my yearly physicals have always shown HBeAg negative while HBeAb positive. After being put on ETV, my tests now come back as eAg 0.099 COI, eAb 0.006 COI, which I assume means negative? My previous fibroscan was 6.4 kPa and the most recent is 4.7 kPa so I believe I don't have any scarring or cirrhosis. I don't know if my doctor is experienced with interferon treatment, my feeling is he is not. I do not believe the genotype was tested, if it was, I was not made aware of what type I have. If I were to start theropy, I think he is thinking about combined since he just refilled my prescription for ETV.

I've been reading a lot of literature about the most recent research and I think I agree with you. My understanding is that the upper limit for INF is < 1500 IU/ml but ideally should be < 1000 to have a better chance of success. I am leaning towards holding off and reevaluating after my next check up to see if my HBsAg values go down.

[StephenCastlecrag]

I guess you were in the Immune Control phase(HbeAg negative chronic disease), then went into the Immune Escape phase(HBeAg negative chronic hepatitis). Some doctors like to add Interferon to speed up the HBeAg seroconversion(from HBeAg positive to HBeAg negative). This is obviously not your case. Good to hear your Fibroscan is 4.7 KPa, the previous higher score may be due to higher ALT when the Fibroscan was taken? Obviously, you have done your research on INF treatments, you may have come across the names Berg and Lampertico, they did of a lot of clinical research on INF and stopping rule, but I believe they don't think it is "ready for prime time". You may also come across their latest bold suggestion - finite treatment using NA! Here is the reference:https://www.natap.org/2021/HBV/PIIS0168827821003056.pdf
All the best.

[Tonyaod]

Hi Stephen, busy weekend with the kids. Anyway, my AST, ALT were consistent in all three fibroscan but I had mild fatty liver in the previous ultrasounds where none were detected this time so I think that's the reason for the improvement in the score.

Interesting proposal with finite treatment with nucs, I'm sure many doctors would call it heresy. HBV is so variable that it's hard to nail down a protocol that works for most people, it seems like a lot of research leads appear to be promising in the beginning but turns out it only works under specific criteria and then only sub-optimally, a real hit and miss venture. It's a hard nut to crack.

[StephenCastlecrag]

Ah, you said it all, very true. For many years, treatments with Interferon, add-on or in sequence, were thought to be able to cure. They did work but only for certain patients. Stopping antiviral treatment may go the same way but at least it does not involve Interferon with its potential side effects, however, it will require the skill of an experienced HBV specialist ( that is, it should not be attempted by patients on their own). Anyway, I am always hopeful.

[melcul]

My honest advice would be to listen to your doctor. He is the most qualified person who knows your history very well.
If he suggested that option, it means that your liver must be in a good condition and the possible benefits outweigh the risk.
I did interferon right at the start of the pandemic, and I was a responder, meaning that my ALT went into 1000, without damaging my liver, but unfortunately, I had to stop it and went on to start tenofovir, which was extremely hard to accept.
In conclusion, I would listen to your doctor. Your other option is to continue taking nucs for many more years to come

[Tonyaod]

Thank you for your response, Mel. I'd have an easier time making a decision if he made a medical recommendation to start this treatment, however, he said he is only informing me of this option now that I am candidate for Peg-Inf, but if it was his decision he would start treatment. My feeling from him is, medically speaking, continuing with current treatment or trying Peg-Inf is equally weighted, one is not more beneficial than the other.

I understand that with Peg-Inf, there is a possibility to be "clinically cured" and this is perhaps the reason for my doctor's preference. My only hesitation at this point is  the cost of treatment paired with a low success rate. It's always easier to gamble with other people's money. ;P