Hi All,
I’m finding it difficult to understand why my HBsAg level is so high. It fluctuates but stays consistently around 25,000 in the quantitative test. My healthcare providers always emphasize focusing on HBV DNA, which has been suppressed since I’ve been on Tenofovir for over three years. Are there any conclusions I can draw from this? Could this indicate a poorer prognosis?
Thank you!
N
Hi @Natti,
In most patients, HBsAg will remain high when being on antivirals. For example, before I started treatment in 2015, my was around 25,000. It has remained around that same mark. The current antivirals do not have as much effect on the HBsAg as it does on the viral load. Your doctor is right since it is the high viral load that leads to severe liver damage. It also means you cannot stop your treatment if HBsAg quantitative remains that high. This is not a problem to stress yourself too much about as it is common for that to remain high. Best, Bansah1
HBsAg can be produced from two sources in the liver cells of a chronic HBV patients - cccDNA and integrated hbvdna in the cell nucleus. HBVDNA can only be produced from cccDNA. Antiviral such as Tenofovir suppresses the production of HBVDNA, but it does not eliminate cccDNA, at best, it prevents the increase in cccDNA. Antiviral has no direct effect on the production of HBsAg. I think the conclusions you can draw are: 1) you are responding to antiviral treatment; 2) your situation is quite normal; 3) you should continue antiviral treatment. As for prognosis, I think it is good as long as you keep HBV DNA to very low, normal ALT, and no or zero progression in fibrosis. In some patients, the cccDNA pool can be reduced during liver cells turnover, leading to a decline in HBsAg, that in turn leads to a restoration of immunological control of HBV and the stopping of all medication.
Hello @Stephenw
My viral load is 10E+04 IU/ml. qHbsAg is 1226 IU/ml. HbeAg negative. Not yet on medication. It is my understanding that my qHbsAg mainly comes from integrated hbvdna. Does antiviral have any effects on integrated hbvdna? Thank you.
Antiviral does not have any effects on integrated hbvdna. I would disagree that your qHBsAg comes mainly from the integrated hbvdna. Your viral load is still pretty high, so that indicates you still have a high number of cccDNA in your liver. They produce hbvdna as well as HBsAg. Because you are HBeAg negative, you are, at best, in the Immune Control Phase, where your immune system is limiting the number of infected liver cells. I would suggest that you monitor your ALT and liver stiffness regularly. There are drugs in development from Replicor to prevent the release of HBsAg in the form of subviral particles from the liver. There are monoclonal HBsAb drugs to neutralize the HBsAg in the blood. There are drugs, such as RNAi and Antisense oligonucleotide, that claim to interfere with the production of HBsAg, from cccDNA and integrated hbvdna.
Dear @babytobeast ,
Some basic molecular biology might help here.
The best known effect of NUCs is to inhibit a viral enzyme called the HBV reverse transcriptase. This effect blocks the maturation of HBV RNA to HBV dsDNA inside the maturing virus. This prevents the secreted virus from being infectious.
The other effect of NUCs (particularily ETV and TDF/TAF) is to suppress cccDNA activity by stimulating innate immunity.
HBeAg, HBcrAg and virus containing only HBV RNA (remember this form is not infectious) are all signs of cccDNA activity. The suppression of HBeAg, HBcrAg and HBV RNA are all common as NUC therapy progresses, just not as fast as the suppression of HBV DNA. When this happens, we know that cccDNA is nearly completely suppressed. Unfortunately, it can still persist in its inactive (latent) form for decades.
The bulk of HBsAg (> 99.99%) is produced independently from virus in the form of subviral particles. It is also produced independently from the activity of cccDNA (and innate immunity) by integrated HBV DNA. The amount of HBV DNA integration steadily increases over the lifetime of the infection. Subviral particles block the immune responses against HBV (and cccDNA) and are the main reason why HBV infection remains chronic.
So in HBeAg positive (cccDNA active) patients, the main effect of NUCs has no effect against HBsAg but the immunostimulatory effect slowly cuts off the production of subviral particles from active cccDNA. This leaves only integrated HBV DNA as the source of HBsAg during NUC therapy. This has been well established in the clinical literature.
In your case, with such a high viral titer without treatment your cccDNA activity is still significant and your HBeAg negativity may be the result of a mutation in the HBeAg gene (precore mutation) which makes the HBeAg undetectable by standard assays. In your case, at least some of the HBsAg is coming from active cccDNA.
The more important issue for you is that with such a high viral titer, your liver function needs to be checked and initiation of therapy considered.
Thanks @availlant and @Stephenw
Hi @babytobeast,
I gave a talk on the basic virology of Hepatitis B that you (and others) might find useful
TT
Thank you @ThomasTu
The metaphor is helpful. It takes thorough understanding of a subject and a lot of EQ to explain well to laymen.