TOPIC: DAAs and Liver Cancer Risk

Here is a link through to the PDF of the draft manuscript that Price refers to above for the retrospective study by S. Pol et al . A much larger study group compared to the previous study that was announced at Barcelona. Per the summary below it appears they found insufficient evidence to support a direct connection between DAAs and increased risk.

"In conclusion, we did not find any evidence that DAA treatment increases the risk of recurrence of HCC in DAA-treated patients compared with untreated patients. In another study, we have also observed a decreased risk of HCC over time in cirrhotic or non cirrhotic patients achieving SVR after DAAs [14].. The prospective follow-up of a large number of patients included in three distinct cohorts of patients reflecting various clinical profiles ensures the quality of our analyses and the confidence in our conclusions."


www.natap.org/2016/HCV/061716_01.htm

Of course, for those of us in this situation and indeed anyone with cirrhosis the above doesn't remove the need for regular and ongoing surveillance of our livers.

Glad to see that thanks Gaj, i keep seeing links to that DAA cancer risk story/headline all the time, and it is misleading. It could put people off treating, which would be crazy, as HCV is the big risk. But I will be monitoring, as you say.

Do you think that Big Pharma could be using this "gossip" method through sleezy channels to discourage people form using generics with the C word as a detriment? After all, it would benefit them in the short term and long term as brand name meds will only go down in price due to new meds reaching the market place so they benefit in both ways. Yes it is a radical theory and far fetched, but co's like GS know how to make/take money from anyone, very sleazily too.
Word of mouth has many benefits, even the lower levels of society who love money more than life itself can throw in shill gossipers to poison markets for their benefit, is not unheard of.
Ok I maybe on a tangent but it is possible, maybe far fetched, but possible.

I hadn't thought of that Sven but maybe- what I just tried was click through a few links to various online articles -within facebook- and in every case the related article that popped up first on offer was that DAA and cancer risk one. But presumably that would be bad news for Harvoni advertising too so I think more likely that we all react to a negative headline, so that story has been looked at more, and is circulating off the number of clicks it gets.

Hi Sven,

Short answer is "No".

The longer answer is that all the studies discussed in this thread were retrospective and conducted via major Hepatology research centres and as a result almost certainly 100% of patients would have used branded DAAs rather than generics so Big Pharma would be shooting itself in the foot to attempt the approach you are suggesting. What we are seeing here is just the normal scientific process of continuing research. One group of researchers think they find some sort of problem in a small study then their peers review that finding and often set up a larger study group that either proves or disproves the original researchers findings. Later, another group of researchers will probably review this area again with an even larger group of patients, just the same as even today there are researchers studying the effects of Aspirin though we already know so much about it.

Also readers should be aware that the studies so far have shown that achieving SVR reduces the risks of getting liver cancer in the first place for those with HCV. What we have been discussing here is the much smaller number of cases where a patient has already had a Hepatocellular carcinoma and then uses DAAs.....and based on the latest and larger study(s) that doesn't seem to be a problem either.

There is no question that disinformation is a tool used by Big Pharma. The rationale for their entire pricing structure is based upon it.

To assume the other guy - in this case, Big Pharma - won't use every dirty trick at their disposal to undermine and discredit the competition simply isn't realistic.

One never has to overthink what the payoff for them is, and should never assume that they will play fair.

ETA: Good watching out, Sven!

"Unexpected high incidence of hepatocellular carcinoma in cirrhotic patients with sustained virologic response following interferon-free direct-acting antiviral treatment" - www.journal-of-hepatology.eu/article/S01...(16)30271-9/fulltext

Unfortunately, there are two cases of occurence of HCC after sof-dac treatment on russian-spoken forum, without previous history of HCC.

Hi Serg

The paper says the patients already had advanced liver disease - could it be possible they had the DAAs too late?

Liver inflammation - killing liver cells - kills cancer cells and normal cells so it is not entirely surprising that treating the HCV, and the damage it is causing, has this result.

It's important to remember that in the absence of treatment liver cell death, liver failure and decompensated cirrhosis is the outcome.

Treating early, before cirrhosis, is a good option.

With cirrhosis the alternative to treatment is allowing the disease to run its course, and that tends to end badly once this stage is reached.

A possible question is - whether DAA treatment increases probability of getting HCC for cirrhotics (comparing to "no treatment") or not? If yes, then things may become complicated... 6.6% per year for treated and 5.2% for people with SVR (data from www.journal-of-hepatology.eu/article/S01...(16)30271-9/fulltext) may seems quite high. Survival with beginning (MELD < 11) compensated HCV-cirrhosis may seems as 80% for 10 years (www.nature.com.sci-hub.cc/ajg/journal/v1.../abs/ajg200931a.html). If i correctly understand, with annual 5.2% (if these data are correct), probability of getting HCC with SVR after DAA treatment during 10 years may be close to 50% for cirrhotics.

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.

Hi Gaj,

My concern is - if DAA treatment increases HCC risk (compared to "no treatment"), then, whether benefits of treatment outweigh its harm "in long-term perspective" or not? It seems, that data from studies look like little bit controversial...

I was diagnosed with HCV-cirrhosis in 2005 and up to now cirrhosis is compensated, and i had not events of decompensation (such as ascites, variceal bleeding, HCC etc.) My lab report (regarding to liver function) is not worse than in 2005. I feel relatively good and not sure that SVR "itself" will sufficiently improve my health... Of course, i want to achieve SVR (and already bought generics for the therapy), but possibility of increased HCC risk after DAA treatment is my main worry. Good managing of HCC requires good medical facilities, it may be difficult for many people in my country. Hope that, really, DAA treatment is not increases HCC risk.

Hi Serg

Re the cirrhosis, I'd say having it would be like sitting on a time bomb.

I'm lucky to have been F0 every time I was tested so it's easy for me to say.

Although I wasn't able to clear the virus prior to Tx I was doing my best to address all the side issues like trouble with joints, thryoid problems, vitamin D deficiency and a host of other things but at age 60 it became more and more clear that I was living on borrowed time.

It's a big call for you.

You have the 'known' which is the condition of your liver and what will happen in the future vs the unknown, which is the question is the cure worse than the disease.

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.

Hi beaches, I wish you to achieve SVR with your therapy!

Yes, cirrhosis is something like time bomb, and question is - whether cure is worse than disease or not. I have some problems with joints too (not very serious), some sleep disorder - but i am not sure that HCV is a cause of such problems instead of other factors... Some of my friends have much more serious joint problems without HCV infection. Really, if i correctly understand, "medical evidence" for many "extrahepatic manifestations" of HCV is not very strong.