Apologies I meant HBsAg loss. The challenge with current assays as that none of them can prove true HBsAg loss, only enough of a reduction to indicate that functional cure of HBV may be present. Reporting “target not detected” or “non-reactive” or reporting a “negative” result does not mean that HBsAg production has been completely removed, but indicates that HBsAg levels are so low that is does not prevent efficient immune control of HBV infection.
In your case, your second test says HBsAg non-reactive, HBV DNA < LLOQ and the presence of small amounts of anti-HBs. In this case the “negative” threshold of 10 U/L comes from levels deemed to indicate successful vaccination. This threshold is not relevant for therapeutic use.
Its hard to know if any of your lifestyle changes impacted your ALT levels or if you just had an immune mediated ALT flare. Your HBsAg reduction suggests the latter.
Are you currently taking antiviral treatment for your infection?
Thank you for your reply. @availlant . all you experts have been amazing in helping us navigate this infection. truly appreciate it
No , i was recently diagnosed as Chronic Hep B ( Dec 2024 ). Dr looked at the low DNA count and said i dont need treatment and to do another test after 6 months (June 2025 ).
Do you think i should consult my Dr to discuss treatment options? In Canada healthcare system is so overwhelmed that Dr’s are in hurry ( understandable as there are many patients waiting) to get you out of the appointment within 5 min and have no time to do a detailed discussions to answer questions or analyze the results.
Your doctor is correct. You do not need therapy. You are actually close to achieving functional cure. Lets see what the next tests show. We will hope for normal ALT!
Firstly, not all patients who become HBeAg negative have mutated virus. In most patients this is a sign of inactivation of cccDNA (but unfortunately not its elimination from the liver). In some patients there is indeed a mutation which prevents the production and or detection of the HBeAg protein.
In most patients, this intermediate control (HBeAg seroclearance) also signals the reduction of immunological activity against since the only antigen now being produced is HBsAg (from subviral particles being produced from integrated HBV DNA).
So the reason why pegIFN works so poorly in HBeAg negative patients is twofold:
It is more difficult for pegIFN to wake up a immune response that is now mostly asleep.
HBsAg blocks the activity of pegIFN to stimulate the immune response.
In unicorn patients (those rare patients [< 5%] with HBsAg < 1000 IU/mL), pegIFN can actually achieve 30% functional cure. This is the problem with all clinical trials now: they are recruiting only unicorn patients.
In my case, since there is a constant fluctuation in HBV DNA, it went from 6.000 to 8.000 in six months, while HBEAG always remained negative. In these terms, I presume it is a mutant virus (but I could be wrong).
This leads me to another question: is it possible to reduce a patient’s HBsAg to the point of making them a unicorn? Or once this barrier is crossed, does it not regress?
Real world studies show that average HBsAg is ~10,000IU/mL
This is a well established fact.
You have to be careful about current “real world” studies since it is not clear how treatment experienced patients influence these newer analysis.
The current phase III study with bepirovirsen is taking a very long time to recruit patients with its requirement for patients to have HBsAg < 3000 IU/mL.
In your case you most likely have a precore mutant.
We know that we can bring people down to HBsAg levels < 10 IU/mL during treatment and they still rebound on treatment. This is becuase HBsAg levels are artificially suppressed and come back after treatment is removed.
With true unicorn patients (who have not undergone multiple treatments with siRNA, antisense and or pegIFN) the HBsAg < 1000 reflects an actual lower production capacity of HBsAg, not an artificial suppression. This is a different setpoint to start from.
these studies says that average qHbsag in e negative “immune control” or nuc suppressed patients is 3.5log. 4 log is average for e antigen chronic hepatitis. Majority of the patients fall in the e antigen negative categories for example my girlfriend is 28 years, e negative nuc naive and her hbsag is 3700.
There much more patients in the low threshold of hbsag than we think and we can treat this these patients first. That would be a good start because functional cure is elusive. There patients are not unicors and much more than 5% of total hepb patients. 24 weeks of siRNA and IFN can be life changing for these patients.
I believe that you are referring to the Scientific Reports study from Taiwan. You have to be careful in interpreting this data as generally applicable to the global population. HBsAg setpoint in Taiwan / China is lower than in other parts of the world. This has also been known for some time. The studies I have provided which include HBeAg negative and positive NA naive and NA experienced patients proves this.
Global prevalence of patients with HBsAg in < 1000 IU/mL is ~ 5% with the average HBsAg 10,000 IU/mL. HBsAg levels in HBeAg negative NA / EU patients averages ~10,000 IU/mL and is even higher in HBeAg positive patients. The unicorn term is appropriate and informative for the patient community. Please do not confuse the patient community by suggesting otherwise.
Now we do know that functional cure of HBV is achieved in 30% of unicorn patients with pegIFN so your idea of achieving functional cure in HBeAg negative Chinese / Taiwanese patients more easily certainly holds merit. We just have not seen functional cure reported for patients beyond the 24 week time point with any of the clinical trials yet (mostly done in China) and we know that HBsAg almost universally rebounds after therapy is removed even in these patients. The phase II bepirovirsen and VIR-2218 + pegIFN studies are examples of this.
REP 2139-Mg is in phase II of clinical development. A small formulation change to REP 1239-Mg is being made based on our latest compassionate use data in extremely difficult patients (see here). This is to ensure antiviral response in every patient.
Once this is completed, registration trials will continue.
