Flare while on TAF

My daughter, now 19, is in the pediatric TAF trial - she is known to have the actual drug for 1.5 years - possibley 2 (the first 6 months were blind). Her ALT/AST had gone to normal levels and her viral load is greatly reduced. With her draw last week, her ALT/AST and bilirubin have spiked. She continues to have the eAG and sAG along with no antibodies. As a college student, she has not been perfect about taking her meds.

What are the thoughts for this sudden flare? I am thinking she is either becoming resistant - though her viral load went down again, or hopefully trying to sero-convert the eAG.

I’d appreciate your thoughts and experiences! Karen

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Hi Karen, I’m hoping that a medical doctor will respond directly to your question but I wanted to ask whether your daughter feels ok with this ALT flare? Just checking. Also, as you seem to know, there is a chance an ALT flare could be related to an eAg seroconversion but my experience with that has been with untreated children. Not sure about a 19 year old who is on treatment? Sorry for not being able to answer your questions, but am hoping that your daughter is otherwise feeling “healthy” and in no distress? Please keep us posted and I’ll be eager to hear what our other medical experts have to say. Thanks so much for sharing this query. Always, Joan

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Thanks for the reply Joan. Feeling OK is relative with her - no physical symptoms but she does have depression and anxiety which seems to be exasperated a bit right now. She lives on campus and is in a very rigorous program that is very demanding on time in the studio. So it is hard to say if she is responding to school or if the flare is the cause. We go back for another draw today and to see the study doctor as they are concerned.

Thanks for your thoughts! Karen

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Hi @klrway,

Welcome to the Community. I hope you can find the answers you seek here. I am a basic/translational HBV scientist and it would be good for a physician to reply too. However, from a virology perspective, tenofovir is really good at suppressing hepatic disease when taken consistently. After the first few months of therapy, I am surprised that a flare is occurring (but I’ll defer to a physician), particularly in a young person. You have identified the likely causes correctly. It could be due to insufficient drug intake as that can cause a flare of liver enzymes as viral levels rise. However, HBeAg seroconversion is also often associated with a flare, so let’s hope that is the case for your daughter.

I wish you the best,

John Tavis

After visiting the specialist today, there were other labs that were out of whack that I was not given info on till now. Her CK was hugely elevated, and again in today’s draw. It looks like it might be complications from having Covid a month ago (despite being fully vacc’d and boosted). Thank you for everyone’s thoughts!

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Thanks Karen for sharing an update. Seems that Covid infections can really have untoward consequences on those with other conditions. How awful for her to go through this as well as the usual college and young adult issues. Having two grown children now, I know that it’s much more difficult to see our kids suffer than it was to suffer ourselves. Best wishes and please keep us posted on your daughter’s situation. Always, Joan

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Thanks for sharing your story, Karen, and welcome to the forum.

Glad that you ended up getting some explanation of the abnormal lab results and hope all is going well with your daughter despite this.

Thomas

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Dear KLRWAY,

Transaminase (ALT and AST) flares during the natural course of HBV infection and during therapy with drugs do occur. In the vast majority of instances, these flares are benign with no alteration of liver function and are considered evidence for the activation of immune response in the liver to remove infected cells. We also know that when patients experience these flares they are more likely to experience HBeAg seroconversion and reduce their viral loads (both good things!).

However, the elevated bilirubin in the case of your daughter also suggests that overall liver function was affected, which can signal damage to the liver. I agree that this could be a complication of SARS CoV-2 infection but I would suggest that follow-up liver function tests would be good to check on her liver function.

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How much flare is considered to be the cause from immune response, i started taking meds from 10/12/21 2years after infection and daignose. Before meds my ltf was normal. First month after meds my AST&ALT 162&165. 5 FEB 22 result was also about normal range. This month result is AST 41 ALT 102. I am 29 years old Asian.
Is this flares cause by my foods habits or some kind of immune reaction.
My viral load was in a million and HBeAg+ before i start meds.
What’s your thoughts on this.
Thanks.

Dear 12345678,

It is important to distinguish ALT / AST / GGT levels in the blood (which are usually a sign of dearth of liver cells) from liver function tests (bilirubin, albumin, INR and platelets) which actually reflect the ability of the liver to perform its functions.

In HBV infection, ALT / AST / GGT levels in many cases, and especially during antiviral treatment are a sign of immune mediated clearance of infected hepatocytes, which does not impact liver function.

We need some more information to answer your questions:

  1. Which antiviral medication are you taking?
  2. What was your viral load (HBV DNA) when these ALT / AST values were observed?

Best regards,

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Hbv dna viral load was in a million taken on October 2021, i was on TDF 300mg from that month itself.
I haven’t test my viral load from last year since its very expensive here,i thought to do viral load test only once a year. But i monitor my lft very 3/4 months.
What does it says if ALT is a little raise but not AST.
Thanks

Hi 12345678,

Do I assume correctly that you live in a country where monitoring of HBV DNA is not covered under a government heath plan?

Its more important to ensure you are experiencing good viral suppression than looking at ALT/AST on a regular basis. We know that ALT/AST flares are always beneficial (e.g. immune mediated) when there is good suppression of viral replication.

If you have been compliant with the daily TDF therapy it is likely that your HBV DNA is very well suppressed (but this should be confirmed with a HBV DNA test). If this is the case, your ALT / AST flare is likely immune mediated. It is normal for ALT to be higher than AST.

The ALT / AST elevations you describe are mild.

Best regards,

Fortunately everything is free in govt hospital in my country but the procedure for viral load takes a lot of time and energy so i prefer private labs for viral load. My ALT after the first 1 month of TDF was 165, but i assume this was a transient flare cause by the initiation of TDF. My second test result i lost it i couldn’t remember exact no. But AST&ALT was still above normal range, last month AST 39 Alt 102. So i should consider 102 is just a mild raise nothing to do with immune reaction.

Apology for too many question.
I want to ask again.
Is there a case or possibility for people who got infected in there adults to loss HBeAg in 1/2 years time with tdf.
I read a WHO articles that says the 4 phases of hbv are not inline with adults,they can be in any phase anytime. As per my understanding from last year i am in immune tolerant phase,Hbeag+ million viral load and normal lft.
Thanks for offering your time and knowledge.

Hi 12345678,

Ok so you should do a HBV DNA test.

Initiation of TDF is not associated with ALT flares. I suspect this flare and the current one are immune mediated but again this is not possible to interpret definitely because we lack the HBV DNA.

HBeAg seroconversion (HBeAg loss with the appearance of anti-HBeAg antibodies) does commonly occur with TDF. Sometimes these are correlated with immune mediated ALT flares.

The natural history of HBV infection is generally a function of duration of infection not of age.

I would like to suggest the following:

  1. Get your HBV DNA tested. Ultimately this should be very low on TDF.
  2. Do not worry about testing liver function so often. TDF does an excellent job of suppressing viral replication and liver disease.
  3. Do an evaluation of your virology / LFT once a year and include HBsAg.

Best regards,

Have you tested the Hepatitis D

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