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TOPIC: DAAs and Liver Cancer Risk

DAAs and Liver Cancer Risk 2 years 1 month ago #14708

  • DrJames
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At EASL two new studies emerged about the risks of developing liver cancer shortly after DAA therapy.

The key points are:

  1. These studies were in patients with cirrhosis, and essentially you need to reach the cirrhosis stage before your liver cancer risk goes up substantially with HCV
  2. Overall it was found that 7% of cirrhotic patients were diagnosed with HCC closely following DAA treatment
  3. In patients who had previously had 1 or more HCC the rate was 29%
  4. In patients who had previously NOT had HCC the rate was 3%

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. www.ncbi.nlm.nih.gov/pmc/articles/PMC2840947/

Take homes:

  1. Treat before you get cirrhosis or HCC
  2. If you are cirrhotic have regular close follow up during and after treatment
  3. If you are cirrhotic and have previously had HCC read #2 again because you have a 1:3 chance of having another HCC in the short term ie within 6 months and this is much higher than expected


More reading:

Medscape: www.medscape.com/viewarticle/862041

And the original manuscript: sci-hub.io/10.1016/j.jhep.2016.04.008
YMMV
Last Edit: 2 years 1 month ago by DrJames.
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DAAs and Liver Cancer Risk 2 years 1 month ago #14744

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Hi Dr Freeman,

I am looking at the 'Nearly one-third of patients with previous HCC recur after DAA therapy April 14, 2016'.

This article that in the middle states:

1. “A history of previous HCC was the strongest predictor of the development of a new HCC after DAA therapy. The more advanced liver disease and younger age were risk factors for HCC recurrence in the subgroup of patients with previous HCC,” Stefano Brillanti,
MD, assistant professor of medicine, University of Bologna, Italy, said during a press conference at the International Liver Congress 2016.

2.This large, retrospective cohort study included consecutive patients (n = 344) without HIV who had hepatitis C-related cirrhosis of Child Pugh A or B. Patients received various DAA combinations, none of which impacted sustained virologic response or HCC occurrence. Researchers followed them for 24 weeks after therapy concluded.

It is not clear to me with regard to:

1. above - having a previous HCC, by definition seems to be a good predictor of a recurrence of HCC, and I expect regardless of being cured of HepC?

2. above - does this just reflect what is said about HCC recurrence anyway? What was reported about quality of life by participants? Does not really says on the medpage website.

This paper seems to give a double meaning - HepC over the long term causes HCC, but at the same time, getting rid of it precipitates HCC?

The rest makes sense, but does not say how long post HCC the 29 per center's were were and what treatment they got - transplant, resection, radiation, lipidol?

Have to admit this virus stuff is all very fascinating.

Yours


Jeff
GT3a 1990 Failed Inter 1998, comb in 2000. HCC 2012
Started 24/52 Sof/Dac 27th October 2015.
1. Bloods 2 October 2015: AST - 165 (20-40), ALT - 265 (5-40), GGT 189 (5-50)
2, Bloods 20 November 2015: ALT etc normal; VL 19
3. Bloods 8 January 2016: AST - 40, ALT - 59, GGT 48 VL RNA UND
4. EOT 12 April 2016 - blood tests: all is well, CT scan: okay
5. AFP 11 June 2016: 4 ref< 11
6. VL July 2016: DET
7. Oct16 start treat - June17 UND
8. Jun 18, lfts okay, platelets a bit low.
Last Edit: 2 years 1 month ago by sabrecat. Reason: editing
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DAAs and Liver Cancer Risk 2 years 1 month ago #14766

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In a nutshell if you have had an HCC and treat with DAAs it is a 1:3 chance you will have another within 6 months.

Quality of life is better treated, but really close follow up is required for this group.
YMMV
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DAAs and Liver Cancer Risk 2 years 1 month ago #14784

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Hi Dr Freeman,

saw your post in another thread about checking AFP's monthly and having scans if any concerns - and thanks for this.

Did notice in the Journal of Hepatology (2016), doi: dx.doi.org/10.1016/j.jhep.2016.04.008 article, that Ribavirin ran a mention in the text as well as the following table of baseline details. The text bit relates to Meissner talking about Ribavirin having some affect on immune cancer control. I also note that in the baseline characteristics, use of Ribavirin was 82%, and the treatment duration was 76% in favour of 12 weeks vs 24.

Of course, seeing my profile and treatment it is easy to see why I would be thinking this way, but aside from this my mind goes back to an ex-partner warding me off the combination Interferon and Ribavirin so many years ago - likened to giving a dog arsenic to treat heart worm was what she said. The first time round with Interferon was not so bad.

I do remember the distinct change in feelings and energy in the first weeks of starting Sof/Dac and then EOT. My question is whether the presenter gave any indication that trying to beat the virus up too quick (12 weeks with Ribavirin) may be asking too much of the old liver?

Otherwise, off to have bloods done and nothing about Hep C surprises me any more.

Yours


Jeff
GT3a 1990 Failed Inter 1998, comb in 2000. HCC 2012
Started 24/52 Sof/Dac 27th October 2015.
1. Bloods 2 October 2015: AST - 165 (20-40), ALT - 265 (5-40), GGT 189 (5-50)
2, Bloods 20 November 2015: ALT etc normal; VL 19
3. Bloods 8 January 2016: AST - 40, ALT - 59, GGT 48 VL RNA UND
4. EOT 12 April 2016 - blood tests: all is well, CT scan: okay
5. AFP 11 June 2016: 4 ref< 11
6. VL July 2016: DET
7. Oct16 start treat - June17 UND
8. Jun 18, lfts okay, platelets a bit low.
Last Edit: 2 years 1 month ago by sabrecat.
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DAAs and Liver Cancer Risk 2 years 1 month ago #14833

  • Price
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It's not just liver cancer, it's other types too. Look, I emailed Dr Robert Gish about it Feb 2015. Here's my email and his answer...

"Dr Gish, I just saw two cases of reactivation of lymphoma after using Sovaldi/Olysio for Hep C.

The first case was a woman who'd had lymphoma 10 years ago and was in remission. Started Sovaldi/Olysio in April. Six weeks later she had anemia and low platelets. By 12 weeks she was so ill she could no longer walk. She had many tests done including bone marrow test, scans, etc with no definite diagnosis.

In July she collapsed at home and was hospitalized. They found increased blood viscosity and had plasmapheresis, platelet transfusions. Was discharged and needed biweekly platelet transfusions.In October she was again hospitalized and had plasmapheresis and was finally diagnosed with Waldenstrom's. She died a few days later from a massive stroke "caused by hyperviscosity of blood".

The second case is one of the Veterans in our group. He'd finished chemotherapy in May 2014 and the lymphoma was in remission. Finished Sovaldi/Olysio November 2014. Aggressive reactivation of the lymphoma 3 weeks later. He has now been in ICU for 8 days.

I've also seen reactivation of rheumatoid arthritis with Sovaldi/Ribavirin and reactivation of psoriatic arthritis with Sovaldi/Olysio.

Yes, the majority is clearing and doing well and only a few having problems. But I'm thinking many of the HIV patients have a history of lymphoma".

Dr Gish responded....

"I have treated many cases of hcv induced lymphoma with daas I have never seen or heard this Have treated over 400 Pts with SOF based therapy. No reactivation

You should report to FDA med watch Agree ?

Thank you
ROBERT G Gish MD"


I swear no one ever believes me.

P
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DAAs and Liver Cancer Risk 2 years 1 month ago #14836

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"Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen." - www.fda.gov/downloads/Drugs/DevelopmentA...ations/ucm094490.pdf
Probably infected in 1977
2005 - diagnosed with HCV 1b, compensated F4, 15 mln viral load, ALT 320
2005-2006 - PegIFN/rib 48 weeks treatment, relapse
2016 - compensated F4, MELD 8-9, ALT 100-160
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DAAs and Liver Cancer Risk 2 years 1 month ago #14839

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I think it happens from too quick of a drop. So here's where using a low carb diet before starting treatment could help you
Use low carb diet to reduce viral load first, so when you start treatment it won't be a big drop. Then use immune adjuvant herbs after Tx like echinacea, astragalus, cordyceps, or even better, use a good prebiotic like ReseT or Del Immune V (lactobacillus rhamnosus) which are anti cancer.

That's what I would do.

P.
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DAAs and Liver Cancer Risk 2 years 1 month ago #14841

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Thanks Price,

I remember from an earlier post of yours about carbs that I rethought my sugar intake, that is I decided I needed to be less of a porker and start losing weight again.

All things said, and my recent visit to the specialist reinforced this, there is more to keeping healthy and alive then using DAA's, waiting for SVR, then expecting to have a long life. Another lesson this bastard virus has apparently taught me.



yours


Jeff
GT3a 1990 Failed Inter 1998, comb in 2000. HCC 2012
Started 24/52 Sof/Dac 27th October 2015.
1. Bloods 2 October 2015: AST - 165 (20-40), ALT - 265 (5-40), GGT 189 (5-50)
2, Bloods 20 November 2015: ALT etc normal; VL 19
3. Bloods 8 January 2016: AST - 40, ALT - 59, GGT 48 VL RNA UND
4. EOT 12 April 2016 - blood tests: all is well, CT scan: okay
5. AFP 11 June 2016: 4 ref< 11
6. VL July 2016: DET
7. Oct16 start treat - June17 UND
8. Jun 18, lfts okay, platelets a bit low.
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DAAs and Liver Cancer Risk 2 years 1 month ago #14842

  • Price
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Here's the letter from EMA:
IMPORTANT: Direct Acting Anti-Virals for hepatitis C under review by European Medicines Agency for reactivating liver cancer in patients

www.ema.europa.eu/docs/en_GB/document_li...rted/WC500204893.pdf
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DAAs and Liver Cancer Risk 2 years 1 month ago #14844

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Yep,

some of us live between a rock and a hard place.

My understanding is that major (not all) risk factors of HCC recurrence were (still are) chronic HCV infection, fatty liver, and the amount of scaring. Hence the idea of being virus free.

I started to lose weight some 11 months before the DAA's with a belief that the liver's 'fattiness' may in some ways reflect the rest of the body's 'fatty' state. Feeling shit with chronic HCV and the attendant lethargy of course does not help with trying to exercise; so black mark against HCV.

Can't change the amount of scaring - but not having HCV may change the situation to where it isn't getting worse.

Chronic HCV - well along came the DAA's.

Of course now there is more than one rock and one hard place: DAA's and possible HCC recurrence vs HCV leading to uncompensated cirrhosis and liver failure (and maybe HCC recurrence).

I don't think there are right and wrong answers for all this, and one thing I know is that for different people there will be different answers, and for just one person like me there will be different answers as well.

Moral for those finding out they are HCV positive early in the piece, consider doing something early - though this may be proved to be wrong in the future.

Maybe titrating the DAA's up and done starting and ending treatment??

Yours


Jeff
GT3a 1990 Failed Inter 1998, comb in 2000. HCC 2012
Started 24/52 Sof/Dac 27th October 2015.
1. Bloods 2 October 2015: AST - 165 (20-40), ALT - 265 (5-40), GGT 189 (5-50)
2, Bloods 20 November 2015: ALT etc normal; VL 19
3. Bloods 8 January 2016: AST - 40, ALT - 59, GGT 48 VL RNA UND
4. EOT 12 April 2016 - blood tests: all is well, CT scan: okay
5. AFP 11 June 2016: 4 ref< 11
6. VL July 2016: DET
7. Oct16 start treat - June17 UND
8. Jun 18, lfts okay, platelets a bit low.
Last Edit: 2 years 1 month ago by sabrecat.
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DAAs and Liver Cancer Risk 2 years 1 month ago #14845

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Here are some very simple guidelines:
  1. If you have HCV treat it now - putting it off will almost certainly be worse
  2. If you don't have cirrhosis, and have never had an HCC, have an AFP at EOT, 3 months and 6 months along with your viral loads and then stop worrying - if it's all clear, you're as good as it gets
  3. If you have previously had an HCC things are not great, and they are not going to get better by delaying treatment. Treat but monitor AFP monthly during the 6 months of treatment and monthly for the 6 months after. After that you can reduce the frequency of monitoring.
YMMV
Last Edit: 2 years 1 month ago by DrJames.
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DAAs and Liver Cancer Risk 2 years 1 month ago #14850

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Hi James could you tell me what a AFP is ? I finished 24 weeks on the 9th april I havent lined up any tests yet. Can you supply any coupons for lab testing , as now we have to pay ? Also do you have any concerns about DAAs that there is now more being revealed that is a down side, or is it just inevitable that there is always a certain amount of damage done with meds, like chemo cure vs damage.Thank You Jill
Geno1a 35years fibrosis 2 or 3 different results from different hospitals ??
24weeks mesochem sof/led as unsure of fibrosis status.
currently UND. No bad side effects
Have svr12 ... waiting for svr 24
I now have SVR 36 weeks.
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DAAs and Liver Cancer Risk 2 years 1 month ago #14851

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Hi Jill,

I've sent you another path form. It's that same as the last one but we have not seen the results. It has the AFP (alpha Feto Protein) HCC (liver cancer) test on it.
YMMV
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DAAs and Liver Cancer Risk 2 years 1 month ago #14852

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Thankyou James should I do that asap or at 4weeks. I dont have a doctor monitoring me, Ive just relied on the forum and you..... which has been a pleasure. Havent felt the need to front up to royal melb as i can imagine they would have a pretty hefty waiting list by now. Can I just get these tests done at a local gp or should i go back to the mothership...royal melbourne. Thank you. Jill
Geno1a 35years fibrosis 2 or 3 different results from different hospitals ??
24weeks mesochem sof/led as unsure of fibrosis status.
currently UND. No bad side effects
Have svr12 ... waiting for svr 24
I now have SVR 36 weeks.
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DAAs and Liver Cancer Risk 2 years 1 month ago #14853

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Hi Dr Freeman.
What simple guideline do you recommended for people who have cirrhosis and have never had an HCC?
Thanks, Michelle
G2b, F4 cirrhosis (fibroscan 29.5 kPa), no prior treatment. Started sof/dac (from Kingswood) 17 Dec 2015 for 12 weeks. Continued with Sovaldi (via PBS) and dac (from Kingswood) 10 Mar 2016 for further 12 weeks.
16 Dec 2015 = ALT 84 AST 99 VL 326,914
19 Jan 2016 = ALT 19 AST 30 VL 22
16 Feb 2016 = ALT 19 AST 27 UND
31 May 2016 = ALT 20 AST 29 UND (EOT 24 wks)
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