Hi Serg,

The choice isn’t one or the other, cirrhosis itself drives increased HCC risk and more so as it progresses. And keep in mind that HCC also has a survival rate, one which is improving all the time due to earlier diagnosis and better treatment options so the comparison survival rate after 10 years isn’t 80% vs 50% as you seem to imply.

The other question is what “survival” with cirrhosis will actually look like after 10 years of continuing liver damage from HCV…..and does that really mean “living”?

As you say it is complicated, more so because we don’t have all the answers but waiting till we do may not be the best option either.

Congratulations Gary, that is a magic number.

Hi Meg,

I’m not an expert but I suspect the answer to your question is basically no and the main reason for shorter treatment is economic (see the second half of post#797 of this link https://fixhepc.com/forum/resistance/164-resistance-and-treatment-failure-mechanisms.html?limitstart=0#797) plus a small desire to reduce length of exposure which is a worthy aim with any drug as long as the Tx is effective.

We need to remember that we can’t be completely certain before treatment how much fibrosis and other liver damage is present in a patient. Also viral load levels are based on how much RNA can be detected in serum, they do not reflect how many hepatocytes are infected. So when Gilead say that 8 weeks harvoni Tx is suitable for low fibrosis, low viral load 1b patients they are really saying “on average to achieve an acceptable SVR rate”.

Also the 95% SVR rate you talk about for 8 weeks harvoni Tx will actually increase to something like 99% if 1b patients are given 12 weeks Tx.

We know that failing treatment is often an indicator of some form of resistance, that is why we repeat Tx with a longer, stronger dose or different drug the next time. So presumably the shorter 8 week Tx results in increased risk of resistance developing compared with longer treatment for the maybe 4% or so extra patients who fail on shorter Tx.

As far as Sofosbuvir S282T resistance goes, it is extremely rare both at baseline and in those who develop viral failure per below quote and is not very good at replicating if it does occur.

In another recent pooled analysis of phase 2 and 3 studies where sofosbuvir based regimen was administered, no S282T variant was detected at baseline. Emergence of this variant was infrequent (1%) in subjects who had virlogical failure. S282T levels declined on average by four fold within two weeks of follow up period confirming low replication fitness of this variant [61].

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690891/

So in most cases any resistance that develops in those who don’t reach SVR during standard Tx will be to something other than Sofosbuvir and that takes us back to Dr James post at the top of the thread.

beaches said: “I thought that HCV mutated quickly anyway,and that’s what made it so hard to treat.”

Yes. Here is a good read on mutants and resistance that Dr James wrote last year.

https://fixhepc.com/forum/resistance/164-resistance-and-treatment-failure-mechanisms.html?limitstart=0

To answer Enkel’s question at the end, Sofosbuvir has a high barrier to resistance. It can happen but is uncommon.

A reminder that members can report unrequested sales pitches either via this thread or just start a new one and the moderators will tidy it up after taking action.

Member Generic has just been banned from this site for unauthorised sales pitches through Private Messages and private chat.

It will be interesting to see if they do allow comments about generics through moderation.

It would be really interesting to see if any European generics patients are allowed to put their good news generics story up on the “Cure Wall”. That would be a great way to spread the word!!!