Hep C Discussion Forum

dmoceri31 · Member

Why are cirrhotics difficult to treat?

Canuck · Guru

Mallani,

You are well versed. I get the rationale of longer treatment for poorly perfused organs, and the "right drugs" which may include IFN/RBV/sofo for the RAV factors, and, the new DAA's just don't have enough feedback yet.

I hear you loud and clear - "get it right the first time ", "the risk is too great". Being TN, this is of great concern to me, as the very tempting new DAA trials (non-IFN/RBV) seem to be motivated to develop "short" treatments, and there seems to be with little actual feedback data yet on RAV's in the new DAA's and trials being offered - this is a worry. I sense your reluctance, on certain treatment regimes, and course lengths.

On another topic - your research on load counts ... I found very little on the subject of "degree" of rebound (to higher levels) post-failure, i.e. TN log 7.01, then treatment failure, then load "typically" increases to ________ ?, and then remains there?? Have you found anything on this subject? Start out 10 million, fail and end up 20 million?? Just a curiosity that I could find nothing on this specifically, just finding all the "regular/standard" load info already out there about the un-importance of load count generally.

Canuck

Tig · Admin

Hi Kiten,

Here is some information and a website that will explain the relationship between the metavir (biopsy) score and that of the Fibroscan. The 1.5 you speak of sounds more like a Metavir score, not a Fibroscan. Cirrhosis on the metavir table starts at F4. Often you will see advanced fibrosis written as F3-4, which is very close to what is considered cirrhosis. As you see in the included statement, cirrhosis is diagnosed when an HCV patient scores 14 or more kPa. Either way, your score of 1.5 is not considered even close to cirrhosis. Hope this helps.

"A person with chronic hepatitis C and a liver stiffness more then 14 kPa has approximately a 90% probability of having cirrhosis, while patients with liver stiffness more then 7 kPa have around an 85% probability of at least significant fibrosis. - See more at: http://hepatitiscnewdrugresearch.com/fibroscan-results-the-scoring-card.html#sthash.EwuPFv19.dpuf"

Tig

kiten_ok · Member

Hi, Mallani

Never thought to come back here again, but after non-response, welcome again) And your Sticky is helpful again. Thank you.

Which Fibroscan means cirrhotics? Mine is F1.5. I heard F3 and higher considered.

Is there any recommends to prevent cirrhotics? Like hls or weight control? What would you recommend?

Paul B · Senior Member

Thanks Mal

It is definitely reassuring to have the facts spelt out.

Cheers,

Paul

mallani · Guru

Hi Paul,

You probably know my answer, but here goes. Your Fibroscan score of 17 indicates cirrhosis. I'm not a believer in 'mild' or 'early' cirrhosis. Cirrhosis can certainly vary in severity, but nobody can agree on how to stage this.

Your RVR gives no indication of your liver state. It merely shows you are Interferon-sensitive ( and probably have the CC allele at IL28B).

At the time, I questioned whether Victrelis was necessary. Patients who are Undetectable after the leadin have a similar SVR rate on Peg/Riba (48 weeks)compared with the Victrelis triple. Anyway, too late to wonder.

Although it is tempting, none of the updated treatment algorithms mentions dropping treatment time to 36 weeks for a cirrhotic. It would be taking a gamble. In your case, you have not developed anaemia, and this would be a slight worry for my doc, who likes to see the Hb drop to below 100. He says that is an indicator that there is an optimal level of Riba. Victrelis is not as potent as e.g. Sovaldi. It needs all the help it can get from both Peg. and Riba. Dosage adherence is vital. It's really up to you, but it's best to get it right the first time when using antiproteases. The risk of persisting RAV's is too great. All the best for your 24 week VL.

Paul B · Senior Member

Hi Mal,

in my position of early stage cirrhosis and having achieved an RVR, does this indicate that possibly my liver may not be as compromised as the fibroscan would suggest?

Also, given that I cleared the virus before the introduction of Victrelis, was their anything to be gained in adding the third drug to the mix?

At my last appointment the nurse mentioned that my treatment may be reduced to 36 weeks, once again, based on the RVR. They will not decide until week 24. What are your thoughts?

Cheers

Paul

mallani · Guru

Hi Bill,

Man, you've had enough Interferon to sink a ship. It just doesn't work for you. Personally, I would give the Sofosbuvir/Peg/Riba a miss and wait a bit longer. It must be hard, but you will only get one go at these new DAA's. I would wait for Sofos/Ledis/Riba and want at least 24 weeks of the stuff. The Abbvie combo is also worth considering, after they have posted the Turquoise 2 results. Good luck mate!

ios9 · Senior Member

Hi Bill,

Did you have a test before starting any of your 3 treatments so to know if it can work or not ? I know many patients here in France who are to be put on Riba and Interferon have a blood test before. It seems they do not need that test with the new treatments ?

The link I have is in french, but may be you could find one in English as it has been published in the "The Journal of Clinical Investigation".

http://www.inserm.fr/espace-journalistes/hepatite-c-en-2011-un-test-pour-predire-l-efficacite-du-traitement-standard.

What they say in the french link is that if patients are + at the blood test, doc do not try classical treatment (Riba and Interferon) but new ones.

here one in English :

http://www.ncbi.nlm.nih.gov/pubmed/21183794

Do

-- Edited by ios9 on Tuesday 1st of October 2013 09:58:20 AM

-- Edited by ios9 on Tuesday 1st of October 2013 10:06:26 AM

Bills · Guru

Hi Malcom

Your explanations of these things is always helpful and I learn of understand them better and better through you.

I have been noticing the Sofosbuvir discussions and Geno 1A/ b and cirrhotics what your saying makes sense to me but I'm not liking the idea of Riba and intf again. I'm a 3 time relapse. Mentally and physically I can take it but I'm just so worried that maybe intef & riba don't work for me ( is it resistance? ) or maybe this blockage you mention. It just kills me to think of another 24-48 weeks and still possible relapse glow in the dark side affects. But I will get back in the ring with the Dragon once I see the success rate for cirrhotic relapse's like me. thanks again

Bill S

ios9 · Senior Member

mallani wrote
AbbVie probably hope that their triple attack will reduce the mathematical chance of RAV's, together with a shorter Rx time. I would not be surprised if the trials found that, for cirrhotics, 24 weeks or more of Rx will be required, and Riba , and even Peg. may also be needed.

Hi Malcom,

The hospital told me that they had received a communication from Abbvie saying that the results from Turquoise II (cirrothic) shows 12 weeks is enough with Riba included.

Also they gave me an addendum from AbbVie saying they might have to put some cirrhotic patients on Riba and Interferon for 48 weeks during or at the end of the Turquoise classical treatment for those who were slow responder or relapsers during the treatment.

Do

mallani · Guru

Hi Matt,

I find it interesting that resistant mutations to the new DAA's have not been discussed. Sofosbuvir is the only one, and so far, it appears that this is resistant to mutations, which is probably why it is so effective. Interferon and Ribavirin are not affected by mutations, which is why they are so useful in mopping up any RAV's. Interferon is not pleasant to take, but it works. Riba also has unpleasant Sx but it will probably still be required in the unstable Genotypes, like 1a.

AbbVie probably hope that their triple attack will reduce the mathematical chance of RAV's, together with a shorter Rx time. I would not be surprised if the trials found that, for cirrhotics, 24 weeks or more of Rx will be required, and Riba , and even Peg. may also be needed.

Blood flow to the liver is unusual, in that more oxygen comes via a vein (portal vein) than an artery (hepatic artery). As the liver's defence to HCV is to slow blood flow through the portal vein, I do not see how this can be increased. Keep reading! Cheers.

Matt Chris · Guru

Hey Malcolm

Thanks for posting this in depth information

Was wondering what effects does using Interferon for the 48 weeks or not using interferon with cirrhotics .

It makes sense from what you reported that Ribavirin still has benefits for cirrhotics. We are seeing some of the newer DAA treatments still includes Ribavirin.

It seems that Abbvie still thinks their is some merit in using Interferon and Ribavirin because they still use it with their current DDA's in their re-treatment protocol.

I guess because all these DDA's are fairly new it has not yet been fully figured out how the best way or combination of Tx that best addresses the cirrhotic patients.

I wonder how many years it will take?

Has their been any other ways to stimulate blood flow in the cirrhotic areas of the liver?

Matt

mallani · Guru

I have had a few PM's about the difficulty in treating cirrhotics. This has been discussed before, but I'll make this a 'Sticky'.

Firstly, only 20-30% of HCV patients will develop cirrhosis, and it usually takes 20-40 years. There are some predisposing factors, such as Genotype 3, obesity, diabetes (fatty liver) and continuing to drink alcohol. Researchers are trying to find a marker to indicate which patients are most at risk, and this will probably be a gene.

Cirrhotics are difficult to treat because they have decreased liver perfusion. Antiviral drugs are not useful unless the virus is exposed to them. The drugs circulate in the bloodstream, but the HCV may 'hide-out' in the liver. We are aware of the thick bands of scar tissue that distort the liver in cirrhosis. These bands of fibrous tissue disrupt the structure, interfering with normal blood flow. At a microscopic level, the hepatocytes are separated from the sinusoids( blood vessels) by a thin fibrous band ( the limiting plate). There are holes (fenestra) in this plate, and the hepatocytes have projections into the sinusoids, so hepatocytes have a very rich blood supply, from the portal vein and hepatic artery. In HCV, the liver's response to injury ( from viral invasion) is to form scar tissue. As early as Fibrosis Stage F2-3, the hepatocyte projections disappear, the fenestra close, and the limiting plate starts to thicken. By F3, the hepatocyte blood supply reduces, and hepatocytes receive less oxygen, and the exposure to the antiviral drugs reduces. By F4, this limiting plate is quite thick, and the blood vessels reduce in size.

The virus eventually has to re-enter the bloodstream, and the antivirals do their job. This takes time, and is the reason for the longer treatment duration required by cirrhotics ( and even F3-4's). The present 48 weeks of treatment is adequate in most cases. The newer DAA's may be more potent, and 24 weeks may be all that is required. Time will tell.

Cirrhotics suffer more severe side effects from the antivirals. This is due to reduced liver function, and the drug breakdown products are less easily processed, and the drug concentrations in the blood may be higher. Cirrhotics usually have some bone marrow depression, so the platelets, RBC's and WBC's all drop quite alarmingly. Some Hepatologists are unwilling to reduce the drug dosages (particularly Riba), as cirrhotics need the highest blood concentrations they can handle. The drop-out rate from treatment side effects is much greater.

This is a simplified version of a complex subject. I hope is of use to some.

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