WHY TAKE TUC
I took Viral DNA test just before heading for hepatectomy. A biopsy taken during the said procedure placed my fibrosis score at 4kPa(little or no fibrosis).My viral DNA came out undetected and yet I had HCC. With this, although I am faithful with my TUC, I have never stopped wondering what help they have had on me and probably some other few of us.
WHY TAKE TUC
I’m glad to see you back on the forum and hope you are going well. In general, antivirals have been shown strongly to limit the amount of liver inflammation and fibrosis associated with Hepatitis B, and this decreases the risk of liver cancer significantly.
Hepatitis B, however, can still cause liver cancer even without liver cirrhosis, through pathways we are still trying to understand (this is part of my research group’s focus). With more research, we will be able to understand why this happens and how we can prevent it.
Welcome back @Kinoti! Glad to read from you.
Imagine I have been away not purely because of HCC but that in the course of the treatment I broke my spectacles and was very down financially to replace them. With poor eyesight, it ment I couldn’t read well.
I was worried about you and I mentioned about you to my wife as well.
I am glad to hear from you.
May God give you healthy and long life.
Thank you. Its not been easy with the Pegasys. Lost weight almost 10kg, with diminishing muscles and general weakness and low appetite etc etc. The good news is my hbv dna as at Dec 2022 was not detectable and HBsAg was 23ui/ml after 30 injections!.Doc advised I could stop injections if I cannot buy more. I will however continue with the tenofovir.
I just got some blood work results and some AST is 60, ALT is normal, ferritin was over 2000 in November but now reduced to just over 1000 thought still high. Liver ultrasound appeared OK. A first doctor says I am responding well to treatment but Awaiting a second doctor to share his comments too.
I may be wrong, but my theory as to how it causes cancer without cirrhosis has to do with how the HBV cccDNA integrates into the host’s DNA. I currently have an occult infection with surface antibodies and no detectable surface antigen, yet from time to time I will show HBV DNA in my blood at very low levels.
It is my belief that the HBV hijacked some of my hepatocytes and mutated their DNA so those cells will do 2 things. (1) create HBV instead of new hepatocytes and (2) turn off the cell’s signaling system that tells my body to destroy them so they can create HBV as long as possible without being eliminated.
As a result, these cells are factories for HBV that are not eliminated by my body as normal hepatocytes would be at the end of their life. But because they only produce HBV and not hepatocytes, their extended life does not result in cancer, instead they cause a continuous HBV infection.
Although my body ignores these HBV factory cells, my immune system recognizes HBV itself as a threat, so the moment these mutated hepatocytes create HBV, my immune system eliminates it, which is why I show up as immune. However, is likely that a few neighboring cells here and there are newly infected before my immune system catches them, but not enough to cause notable liver inflammation.
If that is actually what is happening, it stands to reason that the way my HBV-mutated cells prevent my body from destroying them may play a role in how cancer develops. As some cells are infected by HBV, they may gain the mutation that tells the body they are perfectly fine and to never eliminate them, yet do not gain the mutation that tells them to produce HBV. So what is left are hepatocytes with no off switch that replicate themselves instead of creating new HBV. Without the signaling for the body to destroy them, they continue replicate out of control.
The reason I suspect this comes from what is seen in occult infections where HCC takes place without cirrhosis. They find that there are lower levels of HBV DNA in tumor tissue than in surrounding hepatocytes. This, to me, demonstrates that the cancer cells don’t have the “HBV factory” mutation and do not show up positive for HBV DNA, however, thy do have the “don’t destroy me” mutation that in turn makes them cancer cells.
If this is true and we can find a way to have the immune system recognize cells with the part of the HBV mutation that says “ignore me” and attack them, we can destroy these HBV factories and completely cure occult infections and non-cirrhosis cancer caused by HBV.
This is just a theory though, I’m not a medical professional.
Hi @FelliB ,
HBV DNA being undetectable under TDF therapy is typical and does not indicate functional cure. HBsAg reduction to 23 IU/mL is very rare with TDF and is certainly driven by the pegIFN. This reduction is very good but ideally it should be < 1 IU/mL. You are clearly responding in a positive way to pegIFN. If you can, keep up the pegasys until 48 weeks of therapy are completed. Did you ever have ALT / AST flares during your pegIFN to date?
Thank you for the feedback. Not that I am aware of, but the results of last week had ALT-44, GGT-83.5,AST-60, albumin-4.97,direct bilirubin 0.28 Ferritin - 1018ug/L(reduced from over 2000 in November 2022).Liver US revealed subtle granularity in echotecture, hepatic size14. 1cm (previous liver US was in October 2019 and it was normal with size 13.67cm).
Apart from the ferritin, the rest have always been in range.
Also, AST& ALT had previously ranged 20-24 until these results.
Advice on Peginterferon taken, I have taken 35 injections so far, and I have 5 more available with me. Daily tenofovir continues too.
Dear @FelliB ,
It is difficult to make conclusions about liver disease status (especially with ultrasound) during pegIFN therapy as the liver is trying to do battle with its infection following stimulation of immune responses by pegIFN. I suspect this is the issue with your last ultrasound results.
I have to admit that not seeing any evidence of ALT/AST elevation until now is not optimal but the current small ALT/AST elevations you are seeing may be immune mediated and may get stronger (which is a good thing). I encourage you to at least complete a course of 48 weeks of pegIFN therapy if you can and let us know how your ALT/AST and HBsAg are doing.
Advice most appreciated and its in line with my thinking. Always grateful for all the expert views on this platform that kepp giving some me assurances of good things to come.
I hope the questions @Kinoti is asking gets more attention to guide us all.
Sorry to hear that sir.God will heal you.But if your biopsy is Normal how did you know you have HCC?
When one has HCC, two biopsies are taken, one from the normal liver and the other from the tumor.
Further, there is always a comprehensive analysis done after surgery which gives a complete understanding of the current state of your liver,the surrounding tissues, the tumor, the surgical margin etc.
The rate of HCC in people is generally very low. There is a minor increase in the rate of HCC in people with chronic HBV infection. Unfortunately, this minor rate of increase in the rate of HCC with chronic HBV infeciton is not dramatically impacted when NUC therapy (ETV or TDF/TAF) is started very late in the disease. Reduction in HCC rates are observed when NUC therapy is started earlier in the disease.
The new Chinese HBV treatment guidelines, which indicate treatment immediately for anyone who is HBV DNA positive, regardless of the presence of liver disease or not, is a reflection of this reality. The current treatment guidelines in the US / EU still advise withholding treatment unless liver disease develops, regardless of how long the patient has been HBV DNA positive.
This is bit of a complicated issue HCC incidence varies globally and HCC risk with HBV infection is compounded by other risk factors such as age, ethnicity, the severity of liver disease to mention a few.
A good recent article on this can be found here: https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.31288.
To follow up on @availlant’s great comment, please see here for a free version of that article: Epidemiology of Hepatocellular Carcinoma - PMC. Also the important parts to answer the question are here:
In a US study, the annual HCC incidence was estimated to be 0.42% overall (11), but incidence can vary depending on whether the person has an active HBV infection and/or cirrhosis (12). Cofactors that also increase risk among HBV carriers include demographic characteristics (e.g., male sex, older age, Asian or African ancestry, family history of HCC), viral factors (e.g., high HBV replication levels, HBV genotype, infection duration, coinfection with HCV or HIV), and environmental exposures (e.g., aflatoxin, alcohol, tobacco, obesity, diabetes) (12). […] Further, US data show that HCC risk is extremely low among individuals, including African Americans, who are less than 40 years of age.
Randomized controlled trials have shown that antiviral treatment of HBV infection can achieve sustained reductions in HBV-DNA levels and improve liver function and histology (14).