Hello all,
Can anyone tell me why hepatitis B is considered “chronic” if the patient still tests positive for the virus six months after first testing positive? Why is it believed that a person cannot clear the virus, let’s say, a few years after first testing positive, even if they’ve been taking antivirals for several years? I tested positive for hepatitis B in December 2020 and started taking antivirals in the summer of 2021.
Even if you take medication, you still have Hep B, it’s just suppressed to a really low level. After about six months, the chance to fully clear the virus (and obtain a full cure basically) is about 1% per year.
Thanks for the response. Do you have a source for this figure of 1%?
Check international guidelines on HBV, EASL, AASLD, APASL…
Hi @Barry,
It is called chronic because it becomes long lasting and is harder to clear. That is why it is considered chronic the same way someone with asthma or arthritis etc. will be considered chronic. The asthma/arthritis never goes away and it is always there. That is what the word chronic literally means. Same issue here, it can be controlled but doesn’t go away. Chronic HBV does not go away even with treatments. Current HBV treatments leading to clearing the virus is around 5%. This means the virus is hard to clear once it becomes chronic. I tested positive for HBV in 2014, I have been on treatment since 2015, and I still test positive for HBV. The percentage of treatment leading to cure is very low with the current antivirals we have. I hope this is helpful. Bansah1
Hello Dr. @availlant @Bansah1 @john.tavis
I have a question, How much is the immune system is involved in lowering the HBV DNA viral load once you start NUC Therapy?
for example: if you have a viral load in the millions and you start NUC therapy, and your viral load goes down to almost undetected in six months, is it all thanks to the NUC’s therapy? And, Does the immune system also has his role in helping to lower the viral load?
If the immune system is involved to certain extend, how come that is not able to finish the job, and clear the virus?
Thanks you for your time
Gregory
Hi @Gregory,
Great question. I am not a scientist, but from a patient viewpoint I do believe the immune system plays a role in aiding the antivirals. I believe the antivirals effects the immune system to respond and lead to lower DNA viral load. Our immune system plays a role in almost every health situation our bodies encounter. That is my perspective on your question. We can consider them as two partners working together.
Best, Bansah1
Hi @Barry,
Great question. It is mainly due to looking at when the majority of people clear their infection after exposure. When people are exposed to HBV, most people either clear within 6 months or not at all - there doesn’t seem to be an in-between.
Hi @Gregory,
These are great questions and the simple answer is: we don’t know. It is likely that the immune system does help to some extent, but this is probably very different between different people.
Thomas
Hi Thomas,
Thanks for the response. Is it known why some people don’t clear the virus? I’ve always had a really good immune system, rarely catching viruses of any kind and even when I did I usually recovered very quickly. So I can’t believe how unlucky I am to still have hepatitis B.
I believe you are asking that if NUC therapy is able to bring HBV DNA to undetectable levels and if this involves some aspect of immune response, why does the infection rebound if NUC therapy is removed.
As a class of compounds in general NUCs can stimulate the innate immune response to different extents and by different mechanisms. Thus most potent of these appear to be ETV and TDF / TAF and with these compounds we observe in the clinic declines in markers (HBV RNA, HBcrAg and HBeAg) which are consistent with inactivation of cccDNA (something that does not happen with inhibition of the HBV reverse transcriptase) which can only prevent the formation of infectious virions that contain dsDNA inside). So yes there is a immunotherapeutic component to the antiviral response from these late generation NUCs.
Many viral infections have evolved to be sloppy, producing non-infectious virus (these include viruses like influenza, RSV, HSV and HIV). The evolution of this “sloppy” viral replication has occurred because it helps the actual infectious virus evade the immune response and in some cases, overwhelm it.
In this context, HBV is the king of viruses. It has evolved to not only product large amounts of defective virus (containing only HBV RNA) but also very large amounts of subviral particles. These subviral particles are produced through the already existing production pathway for HDL in liver cells and swamp the blood and liver with large excesses of the HBsAg protein. For every virus there are 10,000 to 100,000 subviral particles. So HBV infection has a very effective mechanism to rapidly exhaust the immune response and prevent detection of virus. To add insult to injury, the HBsAg protein is also able to inhibit immunological functions both in the liver and the blood.
This is how normally healthy persons who can effectively fight normal seasonal infections acquire chronic HBV infection.
The problem with NUC therapy (even with its immunotherapeutic component) is that is does not effect the production of subviral particles and even if cccDNA becomes silenced during NUC therapy, persistent HBsAg is allways produced from integrated HBV DNA. This HBsAg will allow rapid re-activation of cccDNA after NUC removal.
Dr. @availlant Thanks you so much for your explanation.
If the Immune system is overwhelmed by the infection ( High viral load, high liver enzymes etc) let’s say a rather aggressive one, can eventually the immune system once restored to fully function recognize the virus and clear it?
Thanks you again for your time.
Gregory
Thanks availlant for the detailed response. Given that hepatitis B is the “king of viruses”, it baffles me why the vaccine isn’t recommended for everyone. I belong to a “high-risk” group, some of my doctors knew this and yet they never recommended the hepatitis b vaccine to me. This is outrageous.
Dear @Gregory ,
This is common during acute infection and most people ultimately clear HBsAg and develop spontaneous functional cure following initial infection. However, for those persons who lose the battle with HBsAg, immune inhibition remains persistent and infection becomes chronic. In these cases, spontaneous functional cure is very rare and functional cure cannot be achieved unless HBsAg is first cleared with therapy. This is the goal of current therapies in development for chronic HBV infection.
Dear @Barry ,
Indeed one of the cornerstones of modern management of chronic HBV infection is to universally vaccinate everyone who is not infected for HBV. While these guidelines are in place in most countries, this is not yet universally in force around the globe.
It is indeed unfortunate that your doctors were not aware of this but this is as much a fault of poor implementation of policy and education of physicians. Notwithstanding this, most up to date gastroenterologists should understand the importance of vaccination for HBV.
Dear @availlant,
Thanks for your reply. It still seems odd to me though that the pharmaceutical industry is missing out on the opportunity to vaccinate as many people as possible against hepatitis B, including people such as myself in “high-risk” groups. During Covid, it was the other way around: even people in low-risk groups (e.g. young people) practically had a gun put to their head to get jabbed.
Dear @Barry,
This is not a problem arising from the pharmaceutical industry. There are several excellent vaccines available on the market for HBV.
The problem is in the willingness of governments to implement policy changes and also in some locations, the expense of vaccination is too high for governments and or individuals to support.
Hi @Barry,
I wanted to add what @availlant said. Aside from some doctors not being educated about this virus there are some policy issues. For example, for many years in the US HBV policy on testing and vaccination were only for people who were at risk. This limited the number of people who could get tested and vaccinated. But thanks to the Hepatitis B Foundation and their partners, and patient advocates, the CDC changed this policy last year. Now anyone 18 years or older could get tested and vaccinated. As you can see here there is a huge difference between only those at risk versus being open to a large number of people. How these policies are written and implemented matters as well. That is why we continue to advocate and call for change wherever possible. We still have a long way to go and a lot of work to do in eliminating this virus. Great discussion. Bansah1
Hi @availlant and @Bansah1,
What does the hepatitis B vaccine cost? I fortunately come from a wealthy part of the world so I can’t see the cost as being prohibitive. Like I think I said before, babies have been receiving the vaccine for many years now almost routinely after birth. Why not adults? And regardless of government policy, doctors should always act in the best interests of their patients. How long does it take for a doctor to find out a patient’s level of risk from hepatitis B and advise them about the vaccine accordingly? Not long. As I mentioned before, some doctors I have met over the years knew I was in a high-risk category of people for hepatitis B, yet never mentioned this virus or the vaccine against it. I find this unforgivable.
Your experience is not uncommon. Your demographic information is never reviewed by most doctors. They just put that information in their system. I do understand your point, we can advocate and encourage doctors to do more. Vaccines are cheaper with or without insurance in the West compared to low income countries where they are expensive. Access is still a problem. Thanks, Bansah1.
Also supply chain logistics are problematic in many jurisdictions where these vaccines are needed the most due to the requirement for refrigeration.
It should be noted however that deaths due to HBV (mostly cirrhosis / HCC) are rising (from ~880,000 in 2019 to 1.2 million now). This is despite the increasing access to NUC therapy. There are also approximately 1 million newly diagnosed cases of chronic HBV each year.
While efficient worldwide vaccination has the potential to stop new cases down the road, until this happens we have to deal with the effects of chronic HBV infection for the ~300 million people for the next several decades. This requires a treatment which can establish functional cure.