Hi Lisa,

Here is a link to a fairly simple explanation of the process for DAAs. The same basics apply to the various different DAAs being used for HCV treatment although the exact mechanism varies a little depending on which one.

http://esofosbuvir.com/sofosbuvir-drug/sofosbuvir-mechanism-action/

You can also think of it as a bit like a lock and key. Lots of keys will fit the lock but only one will open it and allow the virus to replicate. Normally the virus finds the correct keys in our bodies but if we flood our bodies with lots of faulty keys (Sofosbuvir) that the virus thinks look the same as the one it needs it will use them and block the lock mechanisms stopping the replication from occurring.

So while we often think of the medication killing the virus sort of like a poison or something, it isn’t really. It is just slowing its replication down enough for our immune systems to get back in control and do their job properly.

The side effects (which for most people are fairly mild) are probably a combination of our immune system working hard and as you say the rapid viral die off plus the fact that anything new we add to our metabolism will have some sort of effect until we are used to it.

(Apologies to molecular chemists and biologists everywhere )

Hi Lisa and welcome back.

Sorry you had problems logging back in but good to see you found a way around it. I guess the following advice is now more for others who find themselves in the same situation but an email to help@fixhepc.com or via the public Contact page area stating your old user name and the nature of the problem should allow someone to fix it or reset your password, whichever is required.

Keeping hydrated does seem to help to reduce any side effects that you experience. Here is a good post from Dr James (with link) about adequate levels.

https://fixhepc.com/forum/helpful-hints-during-treatment/712-the-miracle-of-drinking-lots-of-water.html?limitstart=0#12519

In the link you will also find this statement which I’ve also heard from other sources. “Generally, if you drink enough fluid so that you rarely feel thirsty and your urine is colorless or light yellow……….your fluid intake is probably adequate.“

To be clear, I cited the thread not the analogy that was included in a post within it and I made no statements about “negative connotation” or that the analogy should not be used on the forum. I do stand by what I stated.

Only if we wish to be over-melodramatic Serg. Most people would call it a risk-benefit analysis and weigh up the two sides and make a decision that is appropriate for them just like they would with any other medical procedure.

My comment was just a lead in to my thoughts and not intended to imply you shouldn’t be discussing it in this thread. I have struck out that part.

Are you “well” compensated or decompensated as are those in the last study you are now citing? If the first my comments about reduced risk of decompensation still apply. But the study is looking at patients who are already decompensated and have compromised livers to start with. In that cohort a subgroup with certain criteria such as older than 65 and albumin less than 35 were found to be more likely to see an increase in MELD score under treatment. That is not entirely unexpected in a group who are seriously ill to begin with…..but it is a different argument to HCC occurrence.

Hi Serg,

This thread was initially mostly a warning about a potential increased risk of HCC recurrence for those who had a previous history of HCC but you seem to be trying to extrapolate that to show that

…You seem to believe there is a significant risk for all cirrhosis patients taking DAAs and using that to justify not commencing treatment. You should remember that when looking at any risks associated with a disease and its treatment we need to ensure we look at the big picture rather than just focussing on one particular aspect to the exclusion of all others.

While HCC rate in the study graph you link is 6.6% for the first 12 months, in the following 12 months it drops to 1.9% (and still falling) and that needs to be compared with the ongoing annual rate without treatment. If you go back and look at Dr James initial post in this thread he says –

Now you should note that the annual rate of developing HCC in cirrhotic patients is 2-6% so that 3% is essentially what you would expect with OR without treatment. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2840947/

So 6.6% dropping to 1.9% may indicate an increased initial risk followed by a rapid decline….or it may just be within the normal spread of statistical data over any period of time.

Then have a look at the graph marked DC below that one which shows a large and continuing decrease in the rates of liver decompensation for this same group of patients. That correlates well with our overall knowledge about how removing the antagonist of cirrhosis results in a reduction in its progression in line with the comments here https://fixhepc.com/forum/experts-corner/923-daas-and-liver-cancer-risk.html?start=30#20388

As medical research progresses we learn more but there will never be a stage where we know everything. With that in mind we all need to look at our individual situations and take the best medical advice currently available to us and then weigh up whether we treat now or wait. But at some point we do need to make a decision and with that in mind perhaps a reread of the below link may assist?

https://fixhepc.com/forum/experts-corner/320-why-am-i-afraid-to-take-the-medications.html#2770

Hi A.L.,

Of course the problem with your argument is that it is not “Gilead’s own cut price drugs” that people here are using but mostly Indian and a few Bangladeshi manufactured drugs enabled by the fact that India didn’t and Bangladesh isn’t required to recognise a Gilead patent.

Gilead only provided a licence to some of the manufacturers after it realised it was unlikely to achieve the patent control it had applied for in an attempt to harvest some income from the situation. The fact that they have subsequently acquired patent in India is irrelevant to why we can access these medications.

And they certainly don’t “allow this wide open back door” as you state. In fact they attempted to apply rules of supply such as “bottle return before prescription refill” to their licencees to prevent this occurring. Thankfully they have not been very successful in doing that.

Nor have Gilead invested a great deal into research in this case, instead they took a gamble on other’s investments in that area. How much that was truly a gamble can probably be gauged by the 11 billion they overpaid for an asset that the market valued at 7 billion at the time. You could possibly call it an astute or more correctly clever investment but it is one which they have used to price gouge the sick around the world ever since.

By the way, your use of belittlements such as “dedicated witch hunters” in what appears to be a thinly veiled attempt to inflame participants of this discussion does nothing to inform your argument or your audience.

I don’t have answers for your ‘if’ question Serg, and it is just a question not a conclusion. I don’t think anyone does at the moment but hopefully in time we will have enough results and studies to be more confident but until then we need to make the best decision for our own situation we can based on what we know now which includes that HCV and cirrhosis progression and HCC occurrence are difficult to predict but the first two usually worsen with time and can lead to the third.

One thing I will point out is that the study you linked above raises a lot of questions but I’m not sure it provides any answers or any great confidence in its statistics. Some of the variables in that study are:

– We don’t know the exact selection criteria for the total cohort of the study other than that some were in AURIC which specifically excluded interferon and Ribavirin but they then tell us others used Ribavirin.
– Nine different DAA combinations were involved in those diagnosed. And we don’t even know if that was the total for the overall cohort these patients emerged from.
– Three patients had prior HCCs.
– Five of the nineteen relapsed which is high for DAAs.
– One was diagnosed with bone metastasis and subsequently developed a HCC.
– One of those who relapsed was retreated with a second, different (and 10th) DAA combination at which point he developed a HCC.
– The total size of the cohort was just under 200 patients which I believe gives a margin of error of about +/-5% so the real results could have been 0.2% – 11.6% risk.
I realise they excluded some of those from their calculations but that raises questions of why they list them in the first place?

While this study is interesting it seems to raise more questions than it answers so I’m not sure that you should place too much confidence in the percentages that are quoted in it.