Low HBSAG quantitative should I continue interferon

Living With Hep B Treatment and Monitoring
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Should I continue peginterferon after an apparent HBsAg rebound? Looking for an HBV specialist’s opinion

Hello I have with chronic hepatitis B, HBeAg-negative and anti-HBe-positive. I have no fibrosis or cirrhosis (normal biopsy and FibroScan F0), and I have never previously been treated with tenofovir or entecavir.

My HBV history before treatment was relatively stable. HBV DNA from 2021–2025 generally ranged between approximately 250–300 IU/mL. My ALT was normal, and I was considered an inactive carrier. My father had chronic hepatitis B and died from hepatocellular carcinoma at age 69, so I have been particularly interested in achieving a functional cure.

My treatment timeline

I am currently enrolled in a clinical trial involving VIR-2218 followed by pegylated interferon alfa-2a.

  • Baseline HBsAg before treatment: approximately 0.60 IU/mL
  • HBV DNA on January 22, 2026: 54 IU/mL
  • First VIR-2218 dose: January 23, 2026
  • HBV DNA on February 18: 17 IU/mL
  • HBsAg became negative approximately one month after starting treatment.
  • HBsAg was negative on February 22, March 18, and subsequently during treatment.
  • HBV DNA has remained below 10 IU/mL since March 18, 2026.
  • Peginterferon alfa-2a 180 mcg weekly started April 14, 2026.
  • I received six VIR-2218 doses in total, with the final dose in early June 2026.
  • I have continued weekly peginterferon and am now close to completing the planned 24-week course, with the final dose expected around September 22.

The recent issue

On September 3, 2026, my HBsAg screening test unexpectedly came back positive after being negative for several months.

My HBV DNA remains <10 IU/mL.

My ALT has fluctuated during peginterferon treatment, generally in the 60–70s, but bilirubin and albumin remain normal. My white blood cell count and neutrophils have also been suppressed, consistent with interferon treatment, although they have recently started to recover.I do not yet have the latest quantitative HBsAg result in IU/mL.

My questions

  1. Given my very low baseline HBsAg (approximately 0.60 IU/mL), early HBsAg loss, and persistently undetectable HBV DNA, could this represent a transient low-level HBsAg blip rather than a meaningful relapse?
  2. If confirmatory testing is positive but quantitative HBsAg is very low, would there be a rationale for continuing peginterferon beyond the planned 24 weeks—for example, toward a conventional 48-week total course?
  3. Does the fact that I am HBeAg-negative, anti-HBe-positive, and HBV DNA-negative make additional peginterferon more or less likely to help?
  4. If HBsAg remains detectable at a very low level but HBV DNA remains undetectable, would additional interferon be reasonable, or would observation be preferable?

I understand that any extension of treatment would need to be decided by my treating hepatologist. I am mainly interested in how an HBV specialist would interpret this situation and whether there is evidence supporting extended peginterferon in someone who initially achieved HBsAg loss but subsequently has a possible low-level reappearance.

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Hi @A350driver,

Since you are enrolled in a clinical trial, you might not be allowed to continue interferon for longer than the trial protocol states. That being said, you could always discuss it with your investigator, and if they think that staying on interferon would make a big difference to your chances of functional cure, then potentially you could leave the trial so that you’re free to do what you like.

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Thank you, that is helpful. One concern I have is whether the trial investigator might have a conflict of interest in advising me on this decision.

If I leave the trial to continue interferon beyond the protocol, that could potentially affect the study’s data, particularly if I eventually achieve sustained HBsAg loss. Would the investigator have an incentive, consciously or unconsciously, to recommend that I remain in the trial and stop treatment according to protocol so that the study data remain intact?

I am not suggesting that the investigator would intentionally give me biased advice, but I wonder whether it would be more appropriate to seek an independent hepatologist’s opinion before making a decision that could affect both my treatment and the trial’s results.

In my situation, would you consider the investigator’s recommendation sufficient, or would you seek an independent opinion about whether extending peginterferon toward 48 weeks might improve the chance of durable functional cure?

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did you HBsAg ever became undetected / zero ?

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Yes it did for 8 months

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do they not give vaccine when HBsAg drops to zero? vaccine to build antibodies so that HBsAg does not rebound?

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It doesn’t work like that. You still have the CCCdna that current treatment cannot get rid of.

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@ThomasTu @et5656 @Bansah1 @Suwang88 @john.tavis @learnandshare

What do you guys think?

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I think it depends on the investigator. Some of them genuinely want the best for you, whether that means staying in the study or not. When it comes to clinical trial participation, you are free to leave the study at any time, but keep in mind that if you do, then it could affect the integrity of the data. When clinical trials start, they know that they won’t get a 100% completion rate, but they want to minimize the number of people who drop out so that they don’t end up with a sample size that is too small to be statistically significant. I don’t know your investigator, but if you’ve been working with them for a while, you probably have a feel for the level of trust that you have in their opinion. I can’t give you a straight yes/no answer, but I hope this perspective helps.

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Hi all,

I have served on the steering committee of a clinical study and can say that the investigators would prefer that you did not drop out but will fully understand if you do. Their first duty, even in a clinical trial, is to the care of their patients. That is an iron rule for physicians. So in short, don’t worry about the investigator having a conflict of interest in this. Consult with her/him and then make your decision as you feel best.

John

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My understanding is that clinical trials will always plan for participant dropout/attrition, so that there is still sufficient data to make scientific conclusions. Just further reasons to go and talk to your doctor about it, then go from there. No good doctor is going to be upset in helping you achieve the cure that you want.

Cheers,
Thomas

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Thank you John. I appreciate your input

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Hello, and congratulations on what you have achieved so far. HBsAg loss within a month of starting treatment, with HBV DNA undetectable since March, is a result most of us never get to see.

I can only speak as a patient, not a doctor. Around 2010 I was in a trial with Viread plus the same type of interferon you are on. For me interferon was hell. My platelets dropped to around 20k towards the end, they had to add dexamethasone to bring them back, and I only stopped after almost two full years because that was the trial protocol. So I understand very well what you are going through with the low white cells and neutrophils.

From my experience, if you are tolerating it, finish the planned course. Your counts are already recovering, your bilirubin and albumin are normal, and the ALT in the 60 to 70s during interferon is expected. One thing that helped me mentally: interferon is not like the nucleos(t)ide pills. It works through your immune system, so its effect continues for months after the last injection. Many people who ended treatment HBsAg positive at a very low level went on to lose it in the following 6 to 12 months. So a low-level positive at week 24 is not the same as failure.

On your specific question, a screening HBsAg turning weakly positive after several months negative is not unusual, and it does not automatically mean relapse. With a baseline of only 0.60 IU/mL you were already at the edge of detection, so tiny fluctuations can flip the qualitative test. The quantitative HBsAg and a repeat in a few weeks will tell much more than one screening result, and your HBV DNA staying below 10 IU/mL is the reassuring part. Also ask whether anti-HBs has appeared, because that changes the picture.

Whether to extend beyond 24 weeks is a question only your hepatologist and the trial team can answer, since in a trial the protocol usually fixes the duration. But it is worth asking them directly, because outside trials the standard peginterferon course for HBeAg-negative patients is 48 weeks, and you are exactly the type of patient (HBeAg-negative, anti-HBe-positive, very low HBsAg, undetectable DNA, no fibrosis) who is most likely to benefit from interferon.

Something I learned only recently: genotype matters a lot with interferon. Genotype A and B respond best, genotype D (common in Europe) and C respond much less. If you do not know your genotype, ask for it. It will help you and your doctor judge how much more interferon is likely to add.

It is really good that you are pushing for a functional cure. The sooner the better. But one last thing, and you probably know it already given your father’s history: even after HBsAg loss you still need HCC surveillance (ultrasound and AFP every 6 months), because the integrated virus does not disappear. Functional cure lowers the risk a lot, it does not remove it.

Good luck, and please keep us updated on the quantitative result.

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Hello thank you for sharing. Were you able to achieve functional cure? I am approaching week 24th of interferon and so far the side effects have not been to bad. Before starting interferon, I’ve been weight training 4x a week for over one year. I maintain the same regiment on it during interferon. I get mild fatigue ocasionaly but nothing crazy. My investigator said to me he notice people who do well on peg interferon are ones that excercise regularly.

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Hello, glad the side effects are manageable so far. Your investigator is probably right, and it makes sense: interferon works through the immune system, and people who are fit tolerate it better. Keep the training as long as your counts allow it.

To answer your question: no, I did not reach functional cure, but I came a long way. Short version of my story:

  • Started the Viread plus interferon trial in my early twenties, treatment naive, HBeAg positive, high transaminases, viral load in the billions, and quantitative HBsAg somewhere around 70k to 100k IU/mL (I do not remember exactly).
  • After the 2 year trial, HBsAg dropped to about 20k. I continued on Viread, switched to Vemlidy in 2018, and it slowly went down to around 10k.
  • In 2022, still on Vemlidy, I joined the bepirovirsen trial: 3 months full dose, then 3 months half dose. Quantitative HBsAg became undetectable and I lost HBeAg, but no antibodies appeared.
  • After the trial ended I stayed on Vemlidy only. HBsAg bounced back to around 4k, and for the last 2 years it has been stable around 1.5k.

So each treatment gave me a real step down, even when it did not give me the cure. That is why I say interferon can still be a good kick if you can hold it, and your starting point (0.60 IU/mL and undetectable DNA) is incomparably better than mine was.

But be honest with yourself and your doctor. If it starts working against you, end it. Necessary endings are better than being stubborn, and you can always come back to the topic later.

Better treatments are coming anyway. Aligos, the bepirovirsen program, the siRNA combinations like the one you are in. If this round does not close the deal, the next one might, and you will be starting from almost zero HBsAg.

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Wow thank you for sharing your journey. Congrats on making progress on your treatment.

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@A350driver I’m glad that your side effects from interferon are not too bad. I was on bepirovirsen last year in a clinical trial, and some of my side effects were similar to what you got with interferon. My platelets and neutrophils went down. plus I had some fatigue at times, and then my ALT/AST skyrocketed (e.g. 700+ and 350+ respectively).

Unfortunately, bepi did not cure me, but I was HBsAg-negative for almost 6 months after I stopped. Since then, my surface antigen came back, but it’s still <1 as of my last blood draw. I’m hoping it will stabilize there soon, or start going down again. My fingers are crossed for you as well!

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What was your starting hbsag before you start bepi? Thank you for sharing your progress.

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My surface antigen was around 400

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So I had a consult with a hepatologist in the UK and here is the advice be told me.

Peg interferon effect is lasting. The immunity stimulation can last up to 6 months after the last dose. I have a slight better chance of clearing the virus if I continue interferon longer since Im tolerating it well.

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