It’s not the target of that study of course but impact on HBsAg also looks very interesting. What do you think ?
Interesting results … so it has been tested in clinical trials? Your insights Dr Thomas will be much appreciated.
Thanks for sharing this information,
This sort of approach has been seen as risky for treating chronic hepatitis B because if you stimulate the immune system too much against a fully infected liver, you could lead to high liver damage. Safety is always an issue a the front of researchers’ and clinicians’ minds in developing these therapies.
Thanks for the insight. But why nothing happen on that trial ? The dose was to low or they just did not inform about high ALT ? What do you think ? Why is it dangerous ? Because it attacks all cells with HBsAg ?
Ah, good question. The patients were in HBeAg-negative phase, during which the number of cells that are infected is relatively low in the liver (can be less than 1%). Yes, it can be a risk that the T-cells will kill all the cells with HBsAg but you can mitigate the risk by selecting the right patients.
@ThomasTu so even that 1% smashed too fast may cause high inflamation and liver failure, that’s the concern ? How scientists may select right patients ? By some biopsy and measuring (average) number of infected cells ?
Sorry to be confusing, the liver can usually sustain 1% cell death, I am saying that in this case the authors did pick the right patients that have low numbers of infected cells. Biopsy and staining for infected cells would be able to pick this up.
@ThomasTu That’s interesting that you mentioned that the percentage of cells in the HBeAg-negative phase of infection can be less than 1%. Are you able to elaborate on that at all? I’ve been searching but can’t find anything else that mentions that (though I understand it’s part of your specific area of research). Do you have any idea what the usual range of percentage of infected cells in HbeAg-negative hepatitis b is?
This is the paper I usually cite for this statement (though it has been shown in other studies too): https://www.gastrojournal.org/article/S0016-5085(04)00448-2/fulltext?referrer=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F
In Figure 2A, you can see that the average number of cccDNA per cell in the HBeAg-negative patients is 0.01, or 1 per 100 cells.
Indeed, many studies have shown that not all hepatocytes are infected in later stages of an infection (e.g. https://www.gastrojournal.org/article/0016-5085(95)90760-2/fulltext). I don’t think anyone knows why, given these patients will have HBV circulating in the blood that can presumably infect those HBV-negative cells.
Another update for that trial ISCT 2023: Late-breaking SCG101 Data Show 100% HBsAg+ Hepatocyte Eradication and 74.5% HCC Tumour Reduction With Single Dose HBsAg-specific TCR-T Cell Therapy
Do you think that HBsAg drop may persist off-therapy ?
Quite possibly, but we just need to wait for the data to come in. It would be great to have an additional tool in trying to eliminate HBV!