Dear @staystrong ,
You have touched on one of the current and central debates in how therapy for chronic HBV infection should be managed.
The primary goal of current antiviral therapy is to control liver inflammation caused by ongoing active viral replication and prevent the development or progression of liver disease (fibrosis and cirrhosis). Without treatment, liver disease will develop in most people who have chronic HBV infection.
The additional challenge with HBV infection comes from its ability to insert its viral DNA into the chromosomes of infected liver cells (we call this process HBV DNA integration). While this “integrated” viral DNA cannot make virus, it has two negative impacts:
-
It can still support the production of non-infectious “subviral” particles which block immune function against HBV and prevent the establishment of functional cure.
-
HBV DNA integration is progressive with continued viral replication. This increases the number of chromosomal disruptions in liver cells over time and leads to the development of liver cancer. This is the primary reason for why the risk of liver cancer is elevated in people with chronic HBV infection.
So with untreated chronic HBV infection, the risk of developing liver cancer is elevated compared to that in healthy individuals.
With partial cure, a person’s immune system has established control over most (but not all) viral replication in the absence of therapy. So in this case liver inflammation is not present and these individuals are not at risk for the development of liver disease. However, integrated HBV DNA is still present (which is why HBsAg can still be present in abundance) and there is still an elevated risk for developing liver cancer (although this risk appears to be lower than with active chronic HBV infection).
With functional cure, we get complete immune control over viral replication (without any therapy present) which most importantly includes REMOVAL of those liver cells with integrated HBV DNA. In this case, the burden of liver cells containing chromosomal disruptions is very low and in these individuals, the risk of liver cancer is almost as low as in healthy individuals. Incidentally, with the removal of these cells, we also eliminate the production of subviral particles, which is why HBsAg loss persists in the absence of therapy with functional cure.
Now in the case of antiviral therapy, we know that the earlier suppression of viral replication is established, the lower the burden of integrated HBV DNA will be in the liver and also the lower the risk for liver cancer will be. However, in most countries, treatment guidelines recommend the introduction of antiviral therapy only after the appearance of liver disease, which in most people will be after many years (if not decades) of chronic infection. We now know that although effective in halting the progression of liver disease in the the infected population at large, these guidelines have failed to have an impact on the overall death rate from HBV because liver cancer is actually becoming more prevalent in the aging HBV infected population.
China has led the way in altering treatment guidelines, now recommending immediate introduction of antiviral therapy in any person testing positive for HBV DNA, regardless of the presence of liver inflammation / disease or not. There are certainly issues with access to therapy with this approach as most people with chronic HBV are either not aware they are infected or are not prescribed therapy due to existing guidelines.
Given the well established long term safety of existing antiviral therapies, I personally agree with China’s approach and we should look at ways to potentially implement these guidelines for all persons who get diagnosed with HBV.
So a person with partial cure is still at elevated risk from liver cancer and treatment should be considered in such a person. In your case however, your viral replication is already extremely low (32 IU/mL) in the absence of therapy. This likely means your benefit from antiviral therapy will be very marginal. Starting on ETV, TDF or TAF will typically reduce HBV DNA to < 10 IU/mL which is not a great reduction in your case. For someone with normal ALT and HBV DNA 2000 IU/mL (this is still partial cure), the decision is easier to make.
@availlant