Hi all! I’m a PhD student under @ThomasTu working on a few projects revolving around cccDNA, which I’m sure you all know about. Briefly - cccDNA is a stable form of Hepatitis B Virus, which stays in liver cells and is a blueprint which the virus uses to make new virus particles. Getting rid of it is the tricky bit because current drugs (e.g. entecavir, tenofovir, lamivudine) don’t target this form of HBV, only the creation of new virus part of the life cycle.
One way which the body naturally gets rid of cccDNA is through cell division, our lab has shown that when liver cells divides, the cccDNA isn’t carried along into the new cells – somehow it’s lost in the process, resulting in two uninfected daughter cells. So then you’d think that if we can stop cells making new virus (through current therapy), and then wait for mitosis to naturally occur the liver would eventually eliminate all of the cccDNA in all liver cells, meaning a complete cure right?
Well, it’s a little bit more complicated because that’s not really what we see in animal models (humanised mice, chimpanzee, or duck models) or in patient data. Even if we wait until after cccDNA levels are below detectable levels to stop treatment, we see a return of virus levels.
So why is that?
Running theory that our lab has is that not every liver cell wants to divide, there is a rare population of cells (around 1 in 5000) which don’t, meaning that they’ll never lose their cccDNA. These cells basically act as a viral reservoir, hidden caches of virus which sit dormant until the right time (i.e. when stopping treatment!) to reinfect the liver.
Currently my work is focused on looking into different pathways which might cause formation of these “reservoir cells”, as well as potential treatment options to get rid of them. Super cool stuff (at least I think so) and lets me play with some pretty expensive toys (read: professional scientific equipment).
Thanks for reading and happy to take questions