HCC recurrence following Treatment with DAA's

[Pete]

Small sampling but none the less concerning.

April 14, 2016, Geneva, Switzerland: A new study fast-tracked for publication today in the Journal of Hepatology has shown that patients with a prior history of hepatocellular carcinoma (HCC) and who have been treated with direct-acting antivirals (DAAs) for Hepatitis C (HCV) infection have a higher than expected early recurrence rate of their liver cancer than previously thought – with the rate in some subgroups exceeding 40%. The study authors posit that the recurrences could be a result of a weakened immune system following DAA therapy.

http://www.naturalblaze.com/2016/04/study-high-rate-of-early-cancer-recurrence-following-antiviral-treatment-for-hep-c-virus.html?utm_source=Natural+Blaze+Subscribers&utm_medium=email&utm_campaign=64dece6c4d-RSS_EMAIL_CAMPAIGN&utm_term=0_b73c66b129-64dece6c4d-387822569

Pete

[Philadelphia]

Yep. Certainly bears watching. I tweeted to Pierre Gholam today after he tweeted that this seemed to be a key issue coming out of ilc - asked if there was similar data on older peginter/ribs treatments. His response was
@janiekibble don't believe there is a documented peak with older therapies though of HCC risk is well known to persist post cure #ILC2016

[FutureThinker]

So this is potentially yet another reason that these stupid insurance companies need to cover HCV treatment EARLY, vs. when people are at F3 or higher!!!!  FT

[Philadelphia]

Mm mm. With that preliminary data, I would think it certainly provides fuel for insurance overturns if a company only prescribes for F4.

[KimInTheForest]

And then this Medscape article on one of the research doctors reporting at ILC 2016 (Barcelona) on the incidence of liver cancer following DAA treatment:

http://www.medscape.com/viewarticle/862041

From the article:

In a surprising number of patients with hepatitis C and cirrhosis, hepatocellular carcinoma develops within weeks of starting treatment with direct-acting antivirals, new research suggests.

"I do not think that direct-acting antivirals are directly responsible," said lead investigator Stefano Brillanti, MD, from the University of Bologna, Italy.

"The hypothesis is that immune surveillance may be reduced too rapidly," he told Medscape Medical News. "You have an immediate drop in viremia, but also attenuation of inflammation. I think inflammation is a bad thing in terms of hepatitis progression, but it may be a good thing in terms of controlling cancer."

(Me again) I find this theory very interesting (and disturbing) that rapid reduction of liver inflammation by DAAs can promote/trigger a recurrence (or altogether new case) of liver cancer.

These cases aren't limited to cirrhotics or previous occurrences of liver cancer. Is this something we all need to be checked for? Perhaps those of us who had/are having prolonged post-treatments problems? In my case I had many weeks of high fever and drenching night sweats post-tx, with no known cause...

kim

[Luna7]

Very disconcerting..
I knew I was being a bit of a guinea pig going into it though.
Something to keep an eye on for sure, and even more for GT3 it seems.

Do you happen to know of other studies where inflammation is claimed to inhibit cancer?

[KimInTheForest]

Very disconcerting..
I knew I was being a bit of a guinea pig going into it though.
Something to keep an eye on for sure, and even more for GT3 it seems.

Do you happen to know of other studies where inflammation is claimed to inhibit cancer?

I wondered the same thing, Luna - if there are other studies that suggest inflammation limits cancer. I googled that and all I could find was the opposite: chronic inflammation often leads to cancer.

I think the key phrase in that article I quoted is "immune surveillance may be reduced too rapidly". I would theorize that inflammation, as an immune response, is an indicator of heightened immune surveillance. When inflammation is no longer there (i.e., when our liver enzyme numbers drop back to normal during treatment), then that tells us immune surveillance has also been reduced, hence the onset of cancer that we may not have even known was present in a suppressed form. Just my theory of what this all means.

kim

[KimInTheForest]

A little more information about the relationship between inflammation and immune surveillance in cancer suppression in this Wikipedia article on "Cancer immunology" :

https://en.wikipedia.org/wiki/Cancer_immunology

From the article:

Cells of the innate immune system recognize the presence of a growing tumor which has undergone stromal remodeling, causing local tissue damage. This is followed by the induction of inflammatory signals which is essential for recruiting cells of the innate immune system (e.g. natural killer cells, natural killer T cells, macrophages and dendritic cells) to the tumor site. During this phase, the infiltrating lymphocytes such as the natural killer cells and natural killer T cells are stimulated to produce IFN-gamma.

And:

For instance tumour infiltrating lymphocytes are significant in human colorectal cancer. The host was given a better chance at survival if the cancer tissue showed infiltration of inflammatory cells, in particular those prompting lymphocytic reactions.

So it seems that our lymphocytes, necessary for cancer suppression, are triggered by inflammation. Remove the inflammation, and you remove at least some of the body's innate cancer suppression mechanism...

kim

[FutureThinker]

You know, we really are pioneers in this treatment....... Kim was in the first class, Luna and I are in the second.  None of these drugs has any long-term studies yet, they are just too new, my primary concern before starting treatment. Our choice was to continue to wait (I'd already been waiting 4 years) until those studies are done, or "bite the bullet" and forge ahead to getting our lives back. I was so tired of being tired, having my life basically on hold, I was ready to take the plunge! So there is going to be a lot of new data coming out in the next several years that we all are just going to have watch. This is a very dynamic area of medicine right now, still lots to learn. We just have to think positively and get to that SVR goal.  FT

[Gaj]

Good points FT. I made the following comments regarding my thoughts about this study elsewhere so will just reproduce them here.

We do need to be careful with what we read into this recent report. It is really an advisory of initial findings that may not be totally cohort neutral. Due to the retrospective nature of the study there may have been some selection in favour of those with HCC recurrence which is why additional study has commenced.

Also we should keep in mind something one of the study authors(Stefano Brillanti, MD) points out:

"This is a different cancer than elsewhere in oncology — it is a cancer within an advanced chronic disease — so the prognosis, the life expectancy, is related not only to the liver cancer but also to the liver disease and liver function," he explained. "If you don't treat these patients and ameliorate their liver function, and if hepatocellular carcinoma occurs, you have no chance of curing them. But if you ameliorate liver function and they develop hepatocellular carcinoma, you can cure it better because their improved liver function will allow an ablation."

So for those with prior HCC who are now treating with DAAs it should act as an advisory to instigate careful and more regular than usual monitoring during the initial period post EOT.

It was suggested to me that monitoring for those with prior HCC should occur during and for at least 6 months post treatment. They should consider monthly monitoring of blood markers including AFP, with 3 monthly U/S, CT or MRI scans . As I fit the profile I will be following this advice.

[Pete]

Interesting discussion. Would it be prudent to be get an MRI or US prior to starting treatment?  Let me offer this bit of personal histology regarding my experience with DAA's and HCC.

Nov 2014 - CT scan finds 3.6 cm "cyst" left lobe of liver (Treatment Naive)
Dec 2014 - MRI describes "cyst" as complex in nature and being called a "lesion"

March 2015 - Start Harvoni for 12 weeks
June 2015 - MRI indicates lesion is now 1.6cm (>50% reduction in mass)
July 2015 - 4 week post treatment Virus Detected - Treatment Failed

Feb 2016 - Lesion 4.0 cm, now being described as a tumor. 2nd lesion .08 cm noted.
March 2016 - Surgical Liver Resection and RF Ablation performed.
April 2016 - CT scan indicates ablation of the small lesion failed and the "tumor" is now 2.6 cm (300% increase in mass in a month)

Had the first tumor not been found prior to 12 weeks of Harvoni, I would certainly be suspecting the cancer was a result of the treatment at this point.  The tumor actually decreased in mass during treatment.   Unfortunately once the treatment stopped, not only did the virus return, but the cancer returned as well.

I see the doctors again next week for discussion and figure out the next move.  In the meantime, I'm exploring dietary changes in an effort to slow down the advance HCC, but really need to get rid of the underlying cause.

"If you don't treat these patients and ameliorate their liver function, and if hepatocellular carcinoma occurs, you have no chance of curing them"

I hope to be an exception to Dr Brillanti's hypothesis noted above. 
 
Oh BTW - My insurance denied the Viekera/Riba.  But would approve Interferon/Riba. 

Trying to remain positive here folks, Pete

[Gaj]

Hi Pete, based on my limited understanding the risk increase is based on your previous history rather than just commencement of DAA treatment. Previous HCC (or cirrhosis) would require scans. Lack of both seems to indicate no additional risks associated with treatment, so no scans required?

In my case cirrhosis and prior Tx indicated a risk of HCC several years ago which resulted in 6 monthly scans and bloods. 18 months ago my regular checks showed increased scarring and rising bloods and my monitoring was increased to 3 monthly. 12 months ago the first HCC was spotted and resected followed by a second 4 months later which was ablated. Both were caught early and removed cleanly. Since then I have been kept on 3 month checks and the intent was to continue that to March 2017 then review. With these latest reports about potentially increased risks from DAA treatment, which I am currently undertaking, we have now revised plan and will increase the bloods to monthly until end of year as a precaution. No guarantees there of course but the thinking is that rising bloods would be a trigger to do another scan rather than waiting for the three months. (And monthly scans would carry their own risks over that length of time).

I'm not sure how closely the new study information relates to your situation as they noted marked grown during or immediately after treatment whereas you experienced a decrease during Tx. Do you know how soon into the 9 months after EOT that growth started to occur?
One potential good point of your treatment is that while Harvoni didn't cure you I would think it improved you liver function for the period of treatment at least.

I should also note that I'm one of the generics rebels who sourced his own treatment when I became aware of my second tumor and was unable to get the meds I required in an acceptable timeframe via normal channels. There is plenty of information in the Considering Treatment section of this board if you are in a position to take that path.

HCC knowledge and treatment is moving very quickly these days so hoping your doctors will have some positive news and recommendations for you at next week's meeting.

[FutureThinker]

Pete, I understand your concerns. I couldn't pull up the Medscape article. While none of us is happy to see information in the JOH article such as this, let's keep in mind 1) it's one study, 2) 103 patients (low number) & 3) all had a history of treated HCC.  It was my primary concern before starting Harvoni, the lack of long term studies. This study noted the median time between treatment and recurrence was 3.5 months, so sounds like we all need to keep our eyes and ears open, stay abreast of new info as it becomes available, and have regular contact with our physicians. We are the pioneers on this one. FT

[Pete]

My second tumor was identified about 8 mos post Harvoni tx.  I'm obviously disappointed with the results of my surgery, but remain hopeful.  2 weeks post surgery, my surgeon informed me he had difficulty with the ablation of smaller lesion, as it was in a tough spot and hard to access but stated he "got it'.  Not according to the most recent scan.  The resection appears to have been successful, so I'm grateful for that. 

I'm certain my prescription drug provider (CVS) is unaware of my urgent circumstance. I need meds sooner rather than later, and not the Peg/Interferon they  offered up as a treatment option.  Perhaps they will reconsider, following my Doc's appeal. 

Agreed, the lone study sample was small and everyone had advanced liver disease.  Perhaps 27% may have experienced new tumor activity, treatment or not.  The JOH article does give one pause just the same. 

Appreciate the heads up on self-servicing generic meds.  I best start looking into that option in case my appeal drags on.   Thanks for the conversation, it's a blessing to have good folk to talk to about this stuff. 

Pete

[KimInTheForest]

Good luck Pete!  There are new developments coming fast and furious these days - both in terms of HCC and in treating Hep C. You have options. Let's hope your appeal is successful. But if not, the self-pay generic route is working for many right now.

The worldwide Redemption eTrials based in Australia have been used by many people at this point: http://fixhepc.com/home/redemption-etrials.html

Drugs will be shipped to your doorstep. I believe you need to be monitored by a doctor in your home country though.

I look forward to following your progress, Pete, whatever route you go.

kim

[Pete]

Thanks Kim, Always happy to see a reply from you.  I'll for sure be looking further into how to acquire generics as a US resident.

Pete

[FutureThinker]

Pete, I truly hope and pray things work out for you, and soon.  Keep us posted, FT

[Pete]

I'm posting here as a follow up. 

Earlier in this thread, I reported that my recent ablation treatment of a small tumor had failed.  This based on the radiologist report of the CT scan performed on April 13.  That report was in error.  Turns out, I have no detectable lesions at this time. 

Here's what happened. 

While I was advised to have the scan performed at the same medical facility where my surgeon is, I opted not to do so.  Instead, I chose to have the CT scan performed at a radiology clinic closer to home, and have those results sent to my surgeon.  I've done this before with previous MRI without conflict. But things went sort of sideways this time.   

Being unaware that an RF ablation had been performed during surgery on the lower right lobe, he mistook that dark spot on the scan for a 2.6 cm lesion (tumor). It was just the previous ablation site from the March 11 surgery.

Today my surgeon said something like, "We reviewed your case yesterday with our cancer team. Our radiologist and yours have a completely different opinion of your CT scan..."  I too looked at the scan and could see for myself what had happened.

While obviously welcomed news for me, I'm pretty embarrassed by the whole episode. I'm not out of the woods yet, but for now I'll sleep a little better.

Pete
 

[KimInTheForest]

Yippee! That is really good news, Pete! So happy for you. Amazing how much our lives and health and happiness depend on the correct interpretation of lab results. Really glad they caught their error.

best,
kim

[Gaj]

Pete, glad to hear your good news about the CT, now you can focus on beating the HCV.

[FutureThinker]

Pete, GREAT news and I guess this is a reminder that none of us should take anything for granted with these tests, check them and ask any and all questions we have.  Keep up the fight! FT

[Pete]

Thanks for the encouragement.  Hoping to get another shot at the virus, still waiting on appeals.  Have a great weekend everyone.

[sapphire101]

Pete when you mention bloods/labs do you mean were you following your alfafetaprotein (AFP)labs?

Might be a good to add this to our annual check ups post treatment. Of course a yearly ultrasound would be even better, but not likely to be covered by insurance.

all the best to you Pete!
I admire you strength and ability to self advocate.

[lporterrn]

It looks like we may breathe a bit better regarding the post-treatment HCC recurrence concerns: http://www.natap.org/2016/HCV/061716_01.htm