About anti-hbc test

Greeting all, i hope this msg finds all well

I have a question regarding anti-hbc resutls.

Lets assume some is vaccinated and vaccination worked with this person and resulted in high Agsab titer like in 1000s units… lets assume that this person was exposed to hep b virus.

Will his body still generate anti-hbc? Despite having high anti-hbs titer ?

Hi F_beauty
Anti HBs is a protective antibody in the blood that can neutralize and destroy HBV if the person was exposed at the titer level of more than 10 mIU/ml , so the virus is eradicated completely and can’t enter into the liver to form ccc DNA in the nucleus of hepatocyte . It means that the person will not have infection by HBV. If the body immune system is suppressed by immunosuppressive drugs, the low level of anti HBs can’t completely neutralize, then HBV can escape and enter to the nucleus of hepatocyte and increase replication and produce core protein leading to inflammation by adaptive immune response(T&B cell lymphocyte )to eradicate viruses and produce Anti HBc in the blood . Anti HBc that occur is the evidence of HBV infection, it can’t destroy the virus because core antigen locate inside the virus , not at the surface of virus like HBsAg . I hope this may answer your questions.

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Hello I am new to this forum. I appreciate the topics that being discussed here.
Related to this question is what happens when someone was previously infected by Chronic HepB and Asymptomatic/inactive and several years later without knowing about the infection gets HepB immunization. How doe this impact or skew your autoimmune response and the serology markers? I understand that immunization after an infection doesn’t help prevent HepB infection. Does it cause harm or complicates the matter if immunized after a HepB infection?

Hi TomPsu

Wellcome to hepbcommunity.org
According to your questions, there is no evidence that HBV vaccine associated with autoimmune diseases from literature review and meta-analysis.

https://search.app/BgzKrd5DiuDExhX58 )
HBV vaccine don’t like covid 19 vaccines that can stimulate body immune response due to the resemblance between specific human proteins and spike protein , then the body immune system mistakes human proteins as pathogens and trigger autoimmune diseases. Study about effects of HBV vaccine in chronic hepatitis B with occult HBV infection (OBI) which is defined by HBsAg-ve , anti HBc +ve , normal ALT and low level of HBV DNA ,showed that vaccine can increase anti HBs , CD4, CD8 T lymphocytes and HBs specific B cells in peripheral blood but this effect isn’t significantly finding in chronic hepatitis B patients with HBsAg +ve due to the impaired body immune response to HBV both innate and adaptive immunity.

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This answer is very good.

John Tavis

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Hi @TomPsu,

@chul_chan’s answer is good. Note that you may have misspoken when you referred to the antibodies raised by the vaccine as being autoimmune. The definition of autoimmune is an immune response against a normal component of the human body. HBV does not induce autoimmunity, but it is easy to be mix up the terms because hepatitis B disease is primarily caused by the immune cells attacking infected hepatocytes, but the attack is against the HBV proteins in the cells, not a normal part of the cells.

Vaccination in the very large majority of people with chronic infection but no symptoms (sometimes called the “immune tolerant” phase or related terms) has no effect at all. The vaccine adds a very small amount of the HBs protein to the body, but the infected liver is putting out a huge amount of HBs (that is actually part of how it blunts the immune responses to HBV by overwhelming the immune system), so the added HBs barely changes what the immune system is seeing. Folks with “occult HBV” have unusual responses to the virus and may respond to the vaccine in some cases, but I’m not an expert in that area of the HBV literature.

John.

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I had liver resection a year ago due to HCC stage 2. 50% of my liver was taken . My HBsAntigen is still >150. My CA19 and AFP always normal throughout . If my hepatocytes regenerates, will it contain cccDNA even I continue to take TAF with undectable HVBDNA
Thanks for sharing your knowledge .

Thank you for your clear and understandable answer about immune reactions to HBV vaccine in CHB @ john.tavis
Chulapong Chanta. MD. Pediatrics

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ในวันที่ วันพฤหัสบดี, มิถุนายน 27, 2567, 21:48 John Tavis via Hep B Community info@hepbcommunity.org เขียนว่า:

Hi @Ccheng8346,

Your resection appears to have done a good job removing the cancer based on the limited information in this message, but but extensive followup will still needed as your doctor has surely told you. However, so far so good!!!

Your hepatocytes will lose cccDNA as they divide to repopulate the liver. However, not all hepatocytes will divide, and while the cccDNA remains the cells are still infected and can release infectious HBV, which could infect the newly divided cells that had lost cccDNA. I am assuming from your message that you are still on tenofovir and that you are DNA undetectable, but that does not mean that you have cleared HBV given that you are HBs+. We have a hard time telling who has cleared HBV and who still has a low-level infection because the “biomarkers” we use have sensitivity limits and HBs can be made from integrated HBV DNA even if there is no cccDNA left in a cell.

In short, I recommend discussing this carefully with your doctor and following her/his guidance. The conservative option would be to stay on tenofovir or a similar “nucleos(t)ide analog” such as entecavir for an extended period. Although multiple teams around the world are trying to improve how to determine if someone has cleared HBV, there is no firm answer yet.

John.

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Dear Dr Tavis,

Thank you for responding back so short of times I do appreciate sharing your knowledge. I do hope their is drug in the future that helps for a functional cure

With appreciation,

Carlos

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Hi @chul_chan , Can you please simplify the explanation of the above? Did the study show that Vaccinating folks with “OBI” is a good option?

Please advise

Thank you

    Hi bmj1982 
  Thank you for your interesting and great questions. 

First of all, I think we should have the definition of OBI patients in general. It means that CHB patients that have HBsAg -ve ,anti HBs +ve or -ve and anti HBc +ve which are common pattern in OBI patients along with small amount of HBV DNA in blood usually < 200 IU/ml.This condition is different from functional cure due to the presence of HBV DNA in patients with OBI.
Immune system of OBI patients can eliminate serum HBsAg to the lower level that can’t be detected with routine screening test.This may be explained that they still have adequate immune system to a certain level but is not enough to create anti HBs to the high level that can completely neutralize the virus and can’t completely suppress transcriptional activity of ccc DNA , so we can detect low level of HBV DNA periodically release in the blood of these patients.
In contrast with the patients with CHB infection/ hepatitis who are HBsAg +ve , anti HBs -ve and anti HBc +ve which are groups of patients who have chronic HBV and the body’s immune system cannot eliminate HBsAg due to mainly from T cell lymphocytes exhaustion and B cell lymphocytes dysfunction along with impairment of innate immunity.So , these patients will not respond with HBV vaccine which contain HBs Ag surface protein and can’t stimulate dysfunctional B cell lymphocytes to build immunity.
Recently, I have treated a 49 year man with HCV and HIV coinfection in C FREE project. Screening with rapid diagnostic test for HBsAg and anti HBs as routine protocol and the results showed - ve
both. HBV vaccine was given with complete series (0,1,6 mo ) and rapid test was checked after 1 month of complete vaccination. The rapid test showed negative for HBsAg and color line was very faded for antiHBs that I think he had poor immune respond. We decided to check for antiHBc and antiHBs level and HBV DNA level with suspected OBI in this patient. The results showed anti HBc +ve , anti HBs level = 61.48 mIU/ml which was considered to be at low level response and HBV DNA was undetectable due to the patient was taking ARV formula which contained tenofovir.
In general , we use rapid test for screening CHB patients with HBsAg and anti HBs from national guidelines with the reason about cost effectiveness. If we don’t add the screening test like anti HBc , we may misdiagnosed HBV patients with isolated HBc Ab or OBI patients who should receive appropriate treatment especially in high risk patients eg HIV, HCV , PWID, MSM , immunocompromised host etc .
I think that from your question about this study, vaccination may be a good option for these OBI CHB that have no underling comorbidity which may impair the body immune response to eliminate HBV DNA and suppress ccc DNA transcriptional activity that may lead to functional cure in the future. I hope this may help you understand for these complicated HBV virus.
chul_chan
Chulapong Chanta MD. Pediatrics

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This is rally helpful explanation @chul_chan. Thank you

I’m just curious … just theoretically, if OBI patients would have high cure rate with interferon ? As we know peginf works best for people with very low HBsAg

Hi @ sorte
If consider theoretically that it is possible ,however, there are no evidence based and studies about interferon therapy in OBI patients may be due to a small number of patients . Interferon have many side effects so it may not be benefit compared with the risk as a treatment option.
The problematic issues about OBI usually related to HCC formation, viral transmission via blood even with a small amount of virus and HBV reactivation from immunosuppressive therapy due to low persistent cccDNA transcriptional activity which can be prevented with antiviral drugs therapy.
I think that OBI is in a state that closely to functional cure. The question is how to turn OBI into functional cure by stimulating the body immune systems to sustainably suppress and control cccDNA transcriptional activity to prevent viral replication and HBV DNA formation in hepatocytes and release into blood circulation.
chul_chan
Chulapong Chanta MD. Pediatric

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Hi @sorte,

Interesting question! As @chul_chan has mentioned, there are no studies on this, but the basis of your question about peg-IFN is based on functional cure as the output (i.e., if your HBsAg is low, then it is more likely that you will undergo HBsAg loss on IFN therapy). People with OBI already have HBsAg loss, so this outcome doesn’t really inform the potential effect IFN might have on OBI.

Thomas

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I see, I just thought functional cure means HBsAg negative but albo HBV DNA negative. Plus I guess seroconversion to HBsAb+ would be desired output

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