Deciding when to start treatment

Hi @smart55, hopefully Thomas or Andrew will weigh in on your questions. In the meantime, I have a few questions for you about your situation. So are you saying that the pulsatile tinnitus (“the sensation of hearing a rhythmic noise”) first started after you began TDF therapy? Have you spoken to your doctor about this symptom, if it’s new? It would be wise to have your physician evaluate whether the tinnitus is due to another cause before switching therapies. Not to alarm you, but this symptom can also be the result of a blood flow issue rather than a medication side effect? On the other hand, your doctor could be ok with you switching drugs to see if the tinnitus goes away? The short answer to your question is that, yes, you can switch from TDF to ETV (entecavir) without any concern. Thanks for posting your questions and look forward to hearing from others and what you ultimately decide to do. Always, Joan

Dr Vaillant,

I, too, have been experiencing an ALT flare (90 to 115) for a little over a year now. I have had an ultrasound, fibroscan, and biospy and all were fine. My viral load has remained undetectable since I started on Vemlidy 4 years ago. My doctor gave me the option of switching from Vemlidy to Viread just to see if that would change things but I chose not to since it wasn’t definite that the drug was causing the issue. Do you know, on average, how long this flare can last and are there any studies where I can read more about others who have experienced this condition? I want to take your word for it that it’s a good thing but I can’t help but worry about it and am afraid that I am missing something.



Hi Smart 55,

This was an interesting question. This appears to be a very rare complication of TDF therapy which I happened to find in a report of 9 cases of individuals receiving combination therapy for HIV infection which included TDF that developed neurological symptoms. Switching to combo therapy that did not contain TDF resolved these symptoms in each case.

There is no real biochemical basis that I can think of for this connection however, your tinnitus is real so lets consider the following options:

  1. First be sure that you have consulted with your doctor about this regarding any other medications that you may be taking. Also be sure there is no other underlying problem which happened to develop at the same time (but not necessarily caused by) your starting TDF.
  2. Try switching from TDF to TAF. TAF leads to lower systemic exposure of the active metabolite of both these drugs (tenofovir) which may improve your tinnitus.
  3. Try switching from TDF to ETV.

Hope this helps and good luck.

Dear Rebecca,

Even in the natural history of HBV infection (people not receiving therapy) we observe ALT elevations that last longer than 60 weeks at levels higher than this.

The best first question to ask yourself is “How am I feeling?”. Problems with liver function are usually accompanied by feeling unwell or fatigued.

The next item on your checklist is to look at actual indicators of liver function in your test results (bilirubin, albumin, INR and platelets). Whenever you get your ALT measured, these tests should also be performed. I’m going to bet that these are in the normal range.

The third item on your checklist after these is to relax! This ALT elevation is likely a function of an ongoing battle between your immune system and the infected cells in your liver (this is a good thing).

Let us know how things are going and best regards.


@Joan_Block , thank you so much.

@availlant, thank you so much for your answer.

Thanks Thomas and all the experts for organizing this forum, and making this supportive community.

about me: This is Maggie, 43 years old, female, Asian background
I was diagnosed very early (could be infected at birth, but not sure), and I haven’t been on treatment yet.

Family history: both my dad and mum are fine, they are not Hepb affected, but one of my uncles (mother side) is, and died of liver cancer and cirrhosis at his fifties. My grandma (mother side) is Hepb chronic carrier, but she was doing well and died at her eighties (not due to liver issue). She didn’t know she got infected until the she got the blood test after my uncle’s death.

I started regular monitoring since 2013, and before that I only did sporadic tests on liver function and viral load. It was all normal, and viral load was not detected with the old machine (maybe less sensitive). Since 2013, I started the regular monitoring, and started seeing specialists

With the 15 test results so far, the liver function falls in the normal range most of the time. It got elevated ALT three times, AST is always in normal range, but more on the high side in the recent few tests (for example , around 30). Viral load goes up and down between 700 to 3000 (with two high spikes at around 10k). AFP has been stable, but on the high side of the normal range.
Ultrasound has been normal. Fibroscan two years ago is normal.

Now I got different opinions from different doctors:
Doctor A: It is a good time to start treatment now, and we need to bring AST, ALT down to about 19
Doctor B: I should have started far earlier (when the viral load spiked)
Doctor C: I can wait and still keep monitoring (focus more on the viral load, and it is around 1000 and so I am currently fine)

I tend to start treatment now considering my family history, and a bit worried whether it is too late to start. On the other hand, I’m a bit scared that it is a long long term commitment.
I’d like to seek opinions here so that I can make a reasonable decision. Thanks!

Thanks @abcde for your kind words and sharing your story. I think current guidelines would suggest treatment based on your family history of liver cancer.

In terms of feeling like you haven’t started treatment early enough, I think this is not a productive line of thinking. Even if the best time to start treatment was years ago, the next best time would be to start today. Moreover, if you don’t have a doctor willing to prescribe you the drug, it’s really difficult to expect you to be on it. I think you’re doing really well if you have been under regular monitoring for the last ~10 years, so well done on that.

There are many things to consider when considering whether to start treatment, but the major one is usually access and cost, which varies depending on where you are. Here in Australia, it is readily available and cheap (free in NSW), so it isn’t really a problem I deal with. For most people, a pill a day is fairly easy to deal with and side-effects are pretty rare (I haven’t had any problems at all since starting on tenofovir).

Hope this helps,


Thanks @ThomasTu for your kind input! I’m currently in Australia, so access and cost shouldn’t be a big issue at the moment. I’m not sure whether there will be any supply issue on the market like what happend to the toilet paper. Maybe I worry too much.
My doctor would like to put me on Entecavir, and I think I will go with it. I’m still having a few questions about the treatment. It would be appreciated if anyone can share some insights on it.

1.does the chance of drug resistance increase if I accidentally miss the pills?

  1. Also I read some paper talking about elevated ALT being one of the side effects. Is it common? does it only happen at the beginning of the treatment? is it something I need to worry about?

  2. does the antiviral treatment reduce the risk of developing HCC? my limited understanding is that the treatment is able to suppress the virus, so that it make less damage to liver, and therefore reduce the risk of progressing to cirrhosis, which usually leads to HCC. In this case, yes it does help. There is another case where HCC stats without cirrhosis, and even when viral load is low. In this case, antiviral treatment may not be able to help much. Is it correct? I’m not questioning the science behind the treatment, and I think I will start soon. Just trying to understand the whole picture. Thanks!


Dear @abcde,

Great to hear. I haven’t had any problems with maintaining my prescriptions through covid, I always keep a month’s worth on hand and renew my script early.

To answer your questions:

  1. There’s very few cases of entecavir resistance observed, and even if you do get resistance, then you can switch over to tenofovir. Also almost everyone I know has missed doses; a missed one or two days is usually no problem as long as you consistently take it in the long-run.

  2. There were some people that report this, but in most trials it actually reduces ALT levels. I don’t know if there is a known reason why ALTs go up in some people.

  3. Yes, antiviral treatment does reduce both HCC and cirrhosis. The reason is reducing the inflammation. Even if there is no fibrosis, there could be liver inflammation driving liver cancer, and the entecavir reduces this very well.


Thanks @ThomasTu for your time and patience in answering my questions! really appreciated!

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Dear abcde,

In general, NUCs work to suppress viremia which in turn lowers immune mediated liver inflammation and ALT levels. This is the real reason to treat chronic HBV infection - block the continual liver inflammation that leads to progression of fibrosis and the development of cirrhosis.

However, NUCs have a long studied but not widely discussed ability to stimulate immune function (this appears to be strongest for TDF/TAF). So in some people, ALT flares do occur during NUC therapy when there is no rebound of viremia. In these cases, these flares do not affect normal liver infection because they reflect selective removal of infected liver cells by the immune system.

This creates some confusion for patients regarding the worry over ALT levels. A simple guide to follow is:

  1. ALT elevation with increased viral load or changes in liver function are usually a sign to switch NUCs (typically from older generation NUCs like ADV and ETV to TDF and TAF).

  2. ALT elevation with no increase in viral load or changes in liver function is a sign that the immune system is removing infected cells from the liver, in which case you should not change your NUC therapy.

Hope this helps.

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Thanks @availlant for such a detailed explanation! It is really helpful!
Sorry for being pydantic. Can I ask if NUC stand for nucleus? NUC therapy = antiviral treatment?

Can I have one more question?
I remember I’ve read somewhere saying starting antiviral treatment at the wrong time may lead to virus mutation. Is it something I should worry about? My doctors seem not worried at all.

Thanks again for your time!

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Hi abcde,

NUC is a short form for NUCleos(t)ide analog which is the chemical name for the class of compounds that includes ETV, TDF and TAF - sorry for the lingo!

There is no issue with mutation and when you start NUC treatment these cases are exceeding rare with ETV, TDF and TAF.

Best regards,


Thanks @availlant ! what a reassurance! really appreciated it!

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