treatment and its' relationship to liver cancer

Hey guys, I am hearing that tx reduces the risk of developing hcc reguardless of svr. Where does this idea come from? Anyone have any idea why this would be so?

[mikesimon]

http://clinicaloptions.com/Hepatitis/Conference%20Coverage/Barcelona%202007/Tracks/
Special%20Issues/Capsules/226.aspx?Track=Special%20Issues    

* According to Kaplan-Meier estimates, compared with observation, patients who received low-dose peginterferon maintenance demonstrated reduction in HCV-related liver complications
          o Significantly increased survival free from HCC (P < .01)
          o Significantly increased survival free from cirrhosis complications (P < .01)
    * Incidence of nearly all liver complications significantly lower among patients treated with peginterferon compared with those receiving no treatment
          o 18% of patients experienced clinical events during current analysis period

Mike

[mikesimon]

The above post was regarding non-SVRs who treated with maintenance doses. There is a lot of material supporting the fact that achieving SVR significantly reduces the risk of liver cancer(HCC) in HCV patients. I assumed you wanted information for people who are not SVR. If you Google "SVR HCC interferon" I would think you'll find some relevant information.  Mike

[orleans]

is this with maintenance rather than soc/48 weeks?

[orleans]

we crossed, thanks

[Upbeat]

The odds of developing hcc with hep-c is so small that any study involving SVR or maintainence in the total picture is almost meaningless.

                                                                                                          Ron

[orleans]

my gastro dr. told me 1 in 3 chance/ my hepa dr. said 5% per year, this is after cirosis has set in

[orleans]

in a recent post you said you would treat even if the only result was the reduced chance of hcc, any info on that?

[mikesimon]

You said: "The odds of developing hcc with hep-c is so small that any study involving SVR or maintainence in the total picture is almost meaningless."

Even if you had some support for your statement, which apparently you don't, the flat out statement of yours is arrogant as well as misleading. If you really think that statement is true why don't you preface it as your opinion. Anyone reading it hwo didn't know better would think your assertion was a well established fact and from what I have read the chance of developing HCC is increased substantially by having HCV and as the liver architecture deteriorates the chance increases further.

Here is just one of many citations I could provide.


The Natural History of Hepatitis C Virus (HCV) Infection
Stephen L. Chen1,2 and Timothy R. Morgan1,2
1. Gastroenterology Section, VA Medical Center, Long Beach, California
2. Division of Gastroenterology and Hepatology, University of California-Irvine, Irvine, California

See:http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1415841

"The time from HCV infection to cirrhosis is dependent on multiple factors, and cannot be predicted in an individual patient. Virtually all HCV-related HCC occurs among patients with cirrhosis. In a meta-analysis of 21 case-control studies, the risk for HCC was increased 17-fold in HCV-infected patients compared to HCV-negative controls. 54 The results of several retrospective trials show a moderate decrease in the risk of developing HCC among HCV patients treated with interferon. 55-58 This benefit appears to be greater in patients with a sustained viral response rather than non-responders to interferon treatment. 59"

Mike

[Upbeat]

All I know for sure is I have several phd friends from school that have spent years doing research on everything you can amagin.  Their opion of studys like this is you can research this till the cows come home and come up with several different takes.  I look at this kinda stuff for what it is.  Sure there is a 17 fold increase for hcc in hep-c compared to non hep-c .  Duh.   Still  you have a better chance of getting almost any cancer other than hcc.  Sometimes people can't see the forest for the trees.

                                                                                                        Ron

[mikesimon]

Well I have transplant surgeons and hepatologists who say differently but don't you think that's rather vague to put before the members unless you qualify your statement - "My PhD friends tell me......."
But, I like to see at least one published study or article and particularly when I am making a flat out statement like yours. But since you've taken the liberty to make an unsupported bold statement I will as well.

Your PhD friends don't have a clue about the HCV and HCC connection.

Mike

[mikesimon]

You said: "Still you have a better chance of getting almost any cancer other than hcc. Sometimes people can't see the forest for the trees."

You just can't quit, can you? Where is the support for that statement as it applies to chronic hepatitis c sufferers? Can you see anything, much less the trees, clearly? This is a hepatitis board Ron, not a lung or ovarian or brain cancer forum.

Mike

[Upbeat]

Lets see now the rate of hcc is 5 per 100.000 per year. ( The info is out there if you search for it)   Is it higher for hep-c?  Yes.   Is there a good chance you will get hcc with hep-c?  No.  I can't believe how people with hep-c  start living their lives not to die and end up dieing without living.  Its sad.  Can bad things happen to people with hep-c?  Sure.  But to stop living your life and be totally controled by a research and info supplied mainly by the drug companys is like putting your head in the sand.  The vast majority of people will die with the virus and not because of it and this fear factor that has been created reminds me of a president of ours.  Mike you get so wrapped up in this stuff that you seek out dangers.  Life is danger.  Being afraid to live because you might die is worse than the virus.

                                                                                                          Ron

[orleans]

SO, anyone with a definitive answer. Mike, your sited info suggests a moderate improvment with svr folks--not so much with the other 60% (what are the #s in your post? 54,56, etc. page #s?)- my point in this question is what are the benifits in treating,  svr chances (which are low considering the multiple costs)  being one. I've heard that the liver can improve but haven't been able to find much about that--I've heard it improves the risk of hcc but thier doesn't seem to be alot there either. My recent bx didn't come back so good(2-3) but I have yet to go for soc. I keep hopin' for something to tip the balance. thanks guys

[Kit07]

Ron you should do some homework.

Kit
PhD

Hepatocellular cancer: a guide for the internist.

"Hepatocellular cancer is the third leading cause of cancer-related deaths worldwide. Its incidence has increased dramatically in the United States because of the spread of hepatitis C virus infection and is expected to increase for the next 2 decades. "

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17349437&ordinalpos=9&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Hepatic steatosis is associated with increased frequency of hepatocellular carcinoma in patients with hepatitis C-related cirrhosis.

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17487861&ordinalpos=9&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Hepatic steatosis and the risk of hepatocellular carcinoma in chronic hepatitis C.

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=16105127&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus

Viral infections as a cause of cancer (Review).

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17487374&ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

[Upbeat]

Where do you come up with this garbage.  This has nothen to do with hep c or the % of HCC.  Most liver cancers come from other organs and move to the liver and not from hep c. Very misleading. The actual numbers of cancer caused by just hep c is very low.

                                                                                                          Ron

[purplecat]

http://www.oasas.state.ny.us/admed/documents/hepatitisc.pdf see page 21

THERE IS A 7-14% RISK OF GETTING HCC IN 5 YEARS IF CIRRHOSIS IS DUE TO HEPATITIS C.

I've been told the figure is even higher for Genotype 1 but don't have figures to back up that statement. This was told to me by my friend Lee who passed away Aug 05 from HCC and was Geno 1b.



  

[willing]

thanks for those links - that's a good review. I'm actually going in for my hcc ulrasound screen tomorrow at the crack of dawn. It was helpful to see the recommendation set at every 6 months - I've been letting it slide to annually.

Looks like Ron's mind is firmly made up but anyone else interested in the amount of risk involved should take a look at

http://www.cancer.org/downloads/STT/CAFF2007PWSecured.pdf

reference (5) in the review Kit posted.
For this year, total US cancer deaths are projected at 559,650 of which 16,780 due to liver. Obviously not all those are due to HCV, *but*:


"A large, retrospective cohort study confirmed an almost
2-fold increase in the incidence of hepatocellular cancer
from 1975 to 1998 in the United States.2,3 This increase is
primarily related to the spread of hepatitis C virus (HCV)
infection, which peaked in the United States in the late
1980s.4 Given the time lag of 2 to 4 decades between the
onset of infection and the development of cirrhosis, it has
been predicted that the incidence of hepatocellular cancer
will continue to increase over the next 2 decades.4 According
to the American Cancer Society, there will be 19,160
new cases diagnosed and 16,780 deaths due to this disease
in the United States in 2007."

(from page 194 of that review)

[Bill1954]

Mike-

I saw this in my travels and thought it might be of interest to you. Basically, this abstract from the VA reinforces a study you posted last year regarding reduced A1c levels in the HCV treatment cohort.

http://tinyurl.com/2fo8yw

Take care,

Bill

[FlGuy]

Thanks for that succinct phrasing.  It's why I'm playing the game.

[nygirl7]

Both my GI and Doc J. said exactly what Goofy said above
think the thing being missed is that once you have cirrhosis, the HCC risk becomes very real -

And BOTH said to me that even if you did NOT achieve SVR (I am geno 1A and 1B) that it would GREATLY decrease any chance of later GETTING HCC.

Currently I know a 45 year old mother of two who is dying from HCC.  She never realized she was HCV positive until they discovered the tumors.

Why do you think they automatically do an ultrasound BEFORE they even biopsy us if not for the fact that HCV and HCC can go hand in hand.

Please don't spout things saying that they are not related like that is a fact - because it is not. They most CERTAINLY are.

[nygirl7]

Hepatitis C virus (HCV) infection is also associated with the development of liver cancer. In fact, in Japan, hepatitis C virus is present in up to 75% of cases of liver cancer.

In several retrospective-prospective studies (looking backward and forward in time) of the natural history of hepatitis C, the average time to develop liver cancer after exposure to hepatitis C virus was about 28 years. The liver cancer occurred about eight to 10 years after the development of cirrhosis in these patients with hepatitis C

Here is a study from Taiwan if you want to read it
Long-term Effect of Interferon/Ribavirin on Incidence of Hepatocellular Carcinoma

http://www.hivandhepatitis.com/2006roberts/hcv/081506_b.html

During the follow-up period, 5 patients with SVR developed HCC, compared to 11 patients who did not achieve a sustained response (P = 0.0178).

In conclusion, the authors wrote,

[mikesimon]

From my post above:

"The time from HCV infection to cirrhosis is dependent on multiple factors, and cannot be predicted in an individual patient. Virtually all HCV-related HCC occurs among patients with cirrhosis. In a meta-analysis of 21 case-control studies, the risk for HCC was increased 17-fold in HCV-infected patients compared to HCV-negative controls. 54 The results of several retrospective trials show a moderate decrease in the risk of developing HCC among HCV patients treated with interferon. 55-58 This benefit appears to be greater in patients with a sustained viral response rather than non-responders to interferon treatment. 59"

[mikesimon]

I think being an idiot and not even knowing it is worse than death or being afraid you might die and you certainly qualify as an upper echelon idiot. I should have known better than to try to reason with an idiot but I've learned now so that's it for me. Mike

[willing]

"once you have cirrhosis, the HCC risk becomes very real - and as I undertand it - stays real until you have significant regression in damage - and the risk decline at that point is probably theoretical and undocumented."

no argument with the former, but as long-term follow-ups of svrs continue to accumulate characterizing the benefits of svr as "theoretical and undocumented" seems to ignore that evidence (though I agree it's pretty recent).
Along the lines of the study ny cited above, here's another long-term follow up from Italy:

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17326216&ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

which measured : "During a mean follow-up of 96.1 months (range: 6-167) the incidence rates per 100 person-years of liver-related complications, HCC and liver-related death were 0, 0.66, and 0.19 among SVR and 1.88, 2.10, and 1.44 among non-SVR (P<0.001 by log-rank test)."

I just got back from my ultra-sound screen and think that in the future I'll avoid scheduling them at 7:30 on a Monday morning. I asked her what diameter of tumor could be readly detected on the monitor and she thought it was around a few mm - easy to miss among all that blur while you're still thinking about getting a second cup.  And it's only worth it if you can spot them early, else why bother:

"Hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC) worldwide due to the high prevalence of HCV infection and the high rate of HCC occurrence in patients with HCV cirrhosis. A striking increase in HCC incidence has been observed during the past decades in most industrialized countries, partly related to the growing number of patients infected by HCV. HCC is currently the main cause of death in patients with HCV-related cirrhosis, a fact that justifies screening as far as curative treatments apply only in patients with small tumors. As a whole, treatment options are similar in patients with cirrhosis whatever the cause. Chemoprevention could be also helpful in the near future. It is strongly suggested that antiviral treatment of HCV infection could prevent HCC occurrence, even in cirrhotic patients, mainly when a sustained virological response is obtained."

from
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17552029&ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

At least she remembered to tell me when to start breathing again - hate it when they forget..

[GoofyDad]

Mike - I read that the first time through. I was trying to highlight the notion that  HCV does not, by itself, place one at signnificant risk of HCC - which I believe is  what we were hearing from orleans. Once one progresses to Cirrhosis - that's a horse of a different color, as Lady Godiva probably never said as a new steed was led into her bedroom.

Willows - Thanks for the encourraging info on cirrhotic SVRs and HCC risk.    

[GoofyDad]

I think the thing being missed is that once you have cirrhosis, the HCC risk becomes very real - and as I undertand it - stays real until you have significant regression in damage - and the risk decline at that point is probably theoretical and undocumented.    

[FlGuy]

I was unable to access that link on two pc's.  Would you mind re-posting the link?  I would expected that it says something like a1c levels are artificially reduced while on combo tx. Not sure, but interested.

[mikesimon]

I too was unable to link to the article. Mike

[Bill1954]

Sorry gents;

The original URL was 181 characters long, and the long ones tend to break the HTML code using the current format, making the pages we view oh-so-wide.

Let

[mikesimon]

Thanks Bill. When I first suspected this I could find nothing at all about this. I discussed it with my doctors and we all agreed that my HbA1c might be good but it sure wasn't as good as it tested. My normal glucose would have had to have been 45 and we knew that it wasn't. But, it just makes sense that if they are looking at RBCs and extrapolating based on the normal life cycle of red blood cells that with the premature destruction brought on by ribavirin the result had to be too low. Thanks again, Mike

[Bill1954]

You betcha Mike; really good catch and I

[Bill1954]

Despite my best efforts to the contrary, my HDL and LDL have tested low (outside reference range) for quite a while. During treatment, however, values try to get back into a more reasonable range. My *very limited* understanding is that as our liver begins to lose synthetic function, it ceases to produce cholesterol in normal volume. Could this be a sign that we

[FlGuy]

Bill, thanks for the link.  The reduction of a1c was a red herring for me, masked by tx.  Should have known that not being 'obsessive' about a1c would not produce 'actual' results.  Another few months I'll be able to worry less about tx and really address BS.
Anotheer interseting thing about hcv/tx is LDL.  Over the past 20 years or so it's been tested consistently in the 60's.  Only during tx did it break above 100.  Gee, this stuff messes with you.

[mikesimon]

I vastly prefer the Leary days and drugs but I don't think I would like taking them either - at my age. Mike

[Bill1954]

Those were some *interesting* days, my friend. I agree; I

[mikesimon]

I loved both of those acts and still do. I was in Haight Ashbury in 1968 and there were so many acts playing all of the time back then. I wish I could remember more of those days. If you want to indulge in nostalgia I recommend The Band's Last Waltz DVD. In my opinion it is the best music DVD that has been made. If you haven't seen it I urge you to because those were the days and they're pretty well represented in that video. Of course, you have to like The Band. Mike