To treat or not to treat?

[Mugwump]

MELD SCORES slightly off topic..
For Lynn, Eric or anyone who may know or has research info..

My labs before tx 10/2015, Meld score 6.
5 mos post tx labs 10/2016 Meld scored jumped to 8 where it now has remained.

The virus had been und since 1/2016.
So theoretically, since the source of my inflammation AND what was causing cirrhosis has been eliminated, it seems logical to think my meld score would stay the same, or go down if possible, not up.   
What say you??

My suspicion is that some of us have a higher level of cells that are heavily infected and thus are killed and flushed out of the liver during treatment. There seems to be no real sense of the infection staying at even levels during infection with HCV. It might very well be that the level of attack going on just happened to be high at the particular time we are treated.

It seems that HCV has cycles of activity that depend upon how well our immune system is dealing with the virus at any particular time during an infection. Indeed if something comes along that reduces our immunity we are subject to upswings in the levels of liver damage. For years I have suspected that HCV has some kind of genetic clock mechanism that goes through cycles of changes that makes it very hard for our immune system to cope at times.

I do not know why your meld has increased. If your liver enzymes are low and there are no other signs of advancing ascites or marked increased portal hypertension then you should not have a meld that has increased post treatment. I hope your specialist will clarify this for you because it does not make sense.

I took over a year for my levels of bilirubin to drop into the normal range so I know that my liver exchanged a swack of cells post treatment.

I still have discomfort in the hepatic region from the pressure created by an enlarged liver. During treatment my level of bilirubin went up and stayed up for a very long time, I was worried about decompensating but my doctor has assured me there are no signs of ascites happening so the swelling is purely from the gross enlargement of my liver. It has been a source of discomfort for about 8 years and when I get gas it flares up until I fluff which is rather strange. But it makes some sense that if my large intestine is swollen it puts pressure on the membrane which is where the discomfort originates. Thank heavens the liver itself does not have nerves or the pain associated with the inflamed liver would be unbearable I am sure.

Hope your system settles down soon
Cheers
Eric

 

[gnatcatcher]

Greg, I've just spent the last hour searching, and the one possible hint I've found is a single slide near the end of this slide presentation:
https://www.myast.org/sites/default/files/ceot2016/Wiesner_CEOT2016.pdf
The slide says:
               MELD Exceptions
* Liver "diseases" whose natural history is not quantified by MELD
   - Hepatocellular carcinoma
   - Cholangiocarcinoma
   - Neuroendocrine
* Complications of cirrhosis that change the natural history of the disease, independent of liver function
   - Hepatopulmonary syndrome
   - Portopulmonary hypertension
* Diseases expressed in the liver, that do not cause liver disease
   - Familial amyloidosis
   - Hereditary oxalosis
   - Polycystic liver disease

One thing I've noticed during the search is that MELD scores are grouped into large bands, such that all scores within the same large band are given the same mortality %. Thus, someone's MELD score could fluctuate quite a bit without the fluctuation being considered significant unless it crosses from one band to another, in which case suddenly it's considered highly significant. Has the increase in your MELD score been enough to put you into a different band?

Gnatty

P.S. Another possibly useful article:
http://www.medscape.com/viewarticle/543578_3
See bottom half: "Factors Influencing the Prediction Ability of MELD Scoring System"

[Lynn K]

MELD is based on your Creatinine (normal 0.7-1.3 mg/dL), Bilirubin (normal 0.3-1.9 mg/dL),INR (normal less than 1.1) and Sodium (normal 135-145 mEg/L)

Which of your results have changed to cause a change in your MELD score?

Just to add the lowest score possible on the MELD is 6 your score cannot go lower.

[I fightis thetitis]

Only lab that jumped was Bilirubin. Stayed at .9 from 10/25/2015 through 8/22/2016 which was 12 wk EOT.
At 24 wk EOT (10/22/2016 labs) Bilirubin was measured @ 1.5 along with ab pain.
Bili jumped 6 points.
Ironically, and unfortunately, a lot of the folks from the Barcelona and Italian DAA studies were diagnosed with hcc between 12 and 24 eot.

In Jan, I read another article from Japanese GI that mentioned a specific protein has been observed that spikes once virus is eradicated quickly, some folks with advanced liver disease had a reoccurrence and some an occurrence of hcc as the immune system cannot counter it fast enough. Therefore, it grows unchecked and that is what makes it appear more aggressive. Not challenged enough by immune system.

So there is some concern with my Dr. He ordered a battery of test for me..
Feb labs Bili is 1.3. Meld stayed at 8.

Best to everyone,

Greg
PS Just seems odd that body should be healing bc virus is gone, meld should not be going up.

[Lynn K]

Hi

So a lot of things including exercise can cause a rise in billiribin other than HCC. I believe yours was 0.6 not 6 by the way

From WebMd

http://www.webmd.com/digestive-disorders/bilirubin-15434

High values

High levels of bilirubin in the blood may be caused by:
Some infections, such as an infected gallbladder, or cholecystitis.
Some inherited diseases, such as Gilbert's syndrome, a condition that affects how the liver processes bilirubin. Although jaundice may occur in some people with Gilbert's syndrome, the condition is not harmful.
Diseases that cause liver damage, such as hepatitis, cirrhosis, or mononucleosis.
Diseases that cause blockage of the bile ducts, such as gallstones or cancer of the pancreas.
Rapid destruction of red blood cells in the blood, such as from sickle cell disease or an allergic reaction to blood received during a transfusion (called a transfusion reaction).
Medicines that may increase bilirubin levels. This includes many antibiotics, some types of birth control pills, diazepam (Valium), flurazepam, indomethacin (Indocin), and phenytoin
(Dilantin).

I have an abdominal ultrasound every six months along with an AFP (alpha-fetoprotein) test to check for signs of HCC. I will have those tests done most likely for the rest of my life because I have cirrhosis. Having those tests done is normal procedure for those with cirrhosis even if they are cured of hep c as we are at increased risk of HCC even though we are cured. But with cure our risk of decompensation and HCC is reduced.

Have you been having an AFP blood test and abdominal ultrasound or similar like maybe an MRI every 6 months since you were diagnosed F4? How was your AFP test result and how was your most recent ultrasound? Those would be where to look for HCC.

Have you had an upper endoscopy and been immunized against pneumonia, hep a and hep b since you were diagnosed? That is what my doctor had me do right away after I was diagnosed with cirrhosis.

But anyway obviously I don't know why your Bilirubin has increased but there are lots of things it could be that are not liver cancer.

If your Bilirubin reduces you will again have a lower MELD

Here is a link to a MELD score calculator.

https://optn.transplant.hrsa.gov/resources/allocation-calculators/meld-calculator/

Most transplant centers require a MELD of 12 to 15 to be on the list and most people who receive a transplant will have a MELD around 30.

Good luck wishing you the best

[I fightis thetitis]

Well bc the bilirubin went up .6 points in 3 mos from .09 to 1.5 that coincided with the liver pain I had 2 ultras within 2 mos.

Doc ordered endoscopy, colonoscopy, liver spleen scan with nuclear, BTW, why shoot radiation into our bodies for liver scan? wouldn't an MRI be more precise? That may be a GI DR question.

There are some un answered question regarding F4's. Specifically, The role of DAA rapid viral elimination, elevated proteins and immune system not kicking in right away.

Some say they found the smoking gun (a specific elevated protein) other say we are a report or two away from any conclusion that the elevated protein, due to rapid viremia elimination during advanced Liver Disease, poses a quantifiable greater risk.

My story is nothing changed in lifestyle within the 12 weeks my bilirubin increased .06, between 12 & 24 week eot. Dr. is watching me close.

Thank you Lynn and GNatty for your info and research.

Best always,

Greg

[Lynn K]

The endoscopy and colonoscopy should have been done when you were diagnosed with cirrhosis per protocol. We are at risk of developing enlarged blood vessels called varicies most commonly found in the esophagus but they can exist elsewhere. The risk is these blood vessels enlarging to th epoint they could burst and we could bleed to death. On my 3rd upper endoscopy 4 years after I was diagnosed with cirrhosis I was found to have grade 3 esophageal varicies that required banding to prevent a life threatening bleeding incident.

I have never had or heard of the "liver spleen scan with nuclear' I have only had ultrasounds. I have never even had an MRI.  Like you said you should ask your doctor about that nuclear test.

The liver itself has no pain receptor nerves only the capsule that surronds the organ has pain receptor nerve endings. Could be if liver is slightly enlarged it could be pressing against the surrounding membrane. I haven't ever had liver area pain so can't speak to that really either.

Personally I am not buying the increased risk of HCC theory post cure except possibly for those who previously had HCC. I do not believing that curing hep c could increase risk for de novo HCC post cure in any higher probability than what would have occured regardless of cure within the short time frame. True there are some studies that  do raise this concern but many other studies refute that information as well.

Certainly at minimum more data is needed.

Bottom line we are at risk of liver cancer because we have cirrhosis.

I noticed you AFP tests look good. My understanding is if you had HCC you would see a signifigant rise in AFP.

Hope they find out what is going on with you soon.

[Mugwump]

Lynn, isotopes are still used to map blood vessels in some circumstances but they are a little out date, there is also old school radioactive iodine for thyroid scans. In general areas that are covered by the ribs and sternum can be more easily seen this way. These are still used in some places but most modern ultra sounds have more sensitive vascular definition and are considered the standard for most vascular imaging that is accessible. However there are some image processes that are better done with isotopes, especially deep bone scans and the like.

Medical imaging is a field that is changing very quickly and the technology is going forward in giant leaps to say the least because of digital tech.

[gnatcatcher]

Greg, when I saw my hepatologist (head of hepatology in a large hospital system in a metropolitan area) early this month, I asked him about those studies of increased HCC. It was clear that he had read the studies. He thought they had flaws and the only studies that MIGHT be showing an actual effect were those where the patient had had HCC prior to HCV treatment. However, he commented that there is greatly increased surveillance now, which could account for some of the higher rate of HCC recurrence being noted.

But you have studied beyond the question I asked my hepatologist. Here's a suggestion based on Leslie D. Michelson's book The Patient’s Playbook: How to Save Your Life and the Lives of Those You Love. Published studies give contact information for the author(s). If you have specific questions about, for example, whether the smoking gun protein might be an issue for you, why not send a polite email acknowledging the author's expertise and valuable time (offer to pay for a phone consultation), then ask what s/he would recommend in your (succinctly summarized) situation, given the tests that have been done so far.

Nothing to lose from trying -- Michelson interviewed a lot of doctors who indicated they respond favorably to helping people at a loss for a dx, because helping people is why they went into medicine. It might not even cost you a penny.

I hope you get a dx ASAP.

Gnatty

[Lynn K]

Hi Eric

Yeah I did not doubt it was a procedure just not familiar. Like I said I have only had ultrasounds sometimes I wish they would do other imagining like an MRI but I guess my doctors must feel the Ultrasound is adequate. I guess it has Doppler or something that can guage blood flow direction.

[Sergey]

A report about possibility of increased probability of post treatment non-HCC malignancy will be presented soon at EASL (ILC) congress 2017 - https://www.ilc-congress.eu/wp-content/uploads/2017/04/ebooks/2017EASL_WEB_FullEmbargo.pdf

LBP-509
Occurrence and recurrence of malignancies post DAA Treatment in 5.1% of patients - single center experience

A. Issachar1, O. Sneh-Arbib1, M. Braun1, A. Shlomai1, E. Oxtrud1,
Y. Harif1, C. Karavani1, R. Tur- Kaspa1, M. Cohen-Naftaly1.
1Liver institute, Rabin Medical Center, Petah Tikva, Israel
E-mail: assafissa@gmail.com

Background and Aims: Hepatocellular carcinoma (HCC) is an
ominous complication of hepatitis C cirrhosis. The risk of HCC is
reduced among patients cured from hepatitis C virus (HCV) with
interferon based therapy. Antiviral therapy with direct acting agents
(DAA) achieves cure of HCV infection (SVR) in over 95% of the
patients. Sporadic reports suggested that, contrary to the predictions,
an increase in HCC occurrence or recurrence was observed following
therapy with DAA, despite eradication of the virus.
Our aim is to analyze the occurrence and recurrence rate of HCC and
non HCC malignancies in our patients population, treated with DAA
for chronic hepatitis C.
Methods:We have conducted a retrospective study of a prospectively
maintained data base in our center. We reviewed 273 consecutive
HCV patients with or without previous history of HCC who were
treated with DAA, including transplanted patients and reached the
SVR12w.
Results: From July 2014 to January 2017, 273 patients were treated
with DAA and reached the 12 weeks post treatment. SVR was
achieved in 95.2% of the patients. Fourteen patients (5.1%) were
diagnosed with new malignancy between the end of the treatment
(EOT) and 18 months after the EOT (15 months post SVR12w). Six
patients (2.1%) had de novo HCC post treatment, three patients
(1.05%) had evidence of HCC recurrence post treatment. Interestingly,
one of those patients is a transplanted patient (for HCV cirrhosis and
HCC) who had no evidence of HCC in his explanted liver (4 years prior
to the DAA treatment), but developed metastatic HCC post DAA
treatment. Five patients (1.8%) developed non HCC malignancy: one
intrahepatic cholangiocarcinoma and 4 extrahepatic malignancies
(aggressive papillary carcinoma of the thyroid, Squamous cell
carcinoma of the skin, aggressive gastric carcinoma and Hodgkin’s
lymphoma).
Conclusions: Our data indicates an increased risk of malignancy, both
HCC and non HCC, in the first 18 months following DAA therapy. This
may support the theory of a sudden impairment of the immune
system allowing existing preclinical cancer clones to grow.

It may be possible that situation may go beyond discussing possibility of increased post-treatment HCC risks, in direction of risks of non-HCC malignancies too...

[Lynn K]

Having untreated hep c and cirrhosis is also a risk of HCC  as well as potential future complications of advancing cirrhosis. Catch 22

[Sergey]

Yes, each decision brings some risks. To be "guinea pig" or not to be "guinea pig" with new drugs - is a question for many HCV carriers...

[dragonslayer]

I guess figures are needed in order to weigh the relative risk factors of acquiring HCC pre, post, and absent DAA treatment among those with and without cirrhosis for all the various populations involved.  Without that I would think that treating is better than not treating, but without data to back this up, its only my individual bias which leads me to that conclusion.  Id much rather have data to look at that is dispositive  of the issue.

[Lynn K]

Well technically speaking we are well past the guinea pig stage Of Harvoni for example. The true guinea pigs for those who treated during clinical trials. Harvoni has now been available for over 2.5 years.

As for myself I was a guinea pig, I participated in clinical trials in an effort to eridicate the hepatitis C virus.  For me no risk was too great to try to cure my hepatitis C but of course the decision is up to you.

 And bearing in mind I have a risk-taking personality I have made over 200 parachute jumps from airplanes.

[andrew j]

Hi Sergey,

There is a new posting on the homepage you might be interested in:

'Curing Hepatitis C Offers Many Health Benefits To Those With Cirrhosis'.

Best wishes,
A.

[Mugwump]

It seems very logical to me that the results are askew. The reason for this is bloody obvious! The numbers of advanced stage HCV infection being treated.

All the more reason to treat early before HCV has compromised the cell replacement metabolism of the liver.

Yes I can fully understand how a DAA treatment might expose more who are prone to developing cancers.

But also I have personally know close to 20 people who have died of HCV. Of this 3 have died from HCC caused by HCV. This is beyond the stats stated in the group who were treated and went on to develop HCC. But my sample is less people, none of which were around long enough to have a received DAA treatment.

It seems logical that those who go on to develop cirrhosis are at the much higher risk of HCC post DAA treatment. Yes, by itself the sudden rebuilding of liver cells on an already severely compromised vascular and cellular structure of a liver, could very well be the reason why we are seeing more cases of post DAA treatment HCC.

All the more reason to treat early on before the cell replacement metabolism is compromised and the liver should have a much greater chance of rebuilding cells without them becoming genetically screwed up and turning into tumor cells.

It is criminal to not come to this conclusion IMO!

No Sergey, we are not lab rats in this situation we take a risk because we do not want to live with the possibility of infecting others hanging over our heads for the rest of our lives and if we do develop HCC it is a great shame but it is not specifically being caused by the choice to treat the disease.

Yes in future there might be other agents that can be taken along with DAA treatment that might moderate the risk of developing HCC to some extent. But again it will have to be a magic bullet that specifically targets HCC or perhaps helps natural interferon production that might protect us from HCC. But until it is know exactly which interferon variant protects us from HCC and exactly how to produce and administer them effectively the point is moot.

Eric 

[Sergey]

Lynn, over 200 parachute jumps are impressive! I feel, that my personality is not so risk-taking. Your cirrhosis was not very beginning in 2014, if I were you, I had started treatment too (also, there was no controversial data about posttreatment cancer risks in 2014). I wanted to get Harvoni in 2014, but it was not accessible for me. If it was accessible, I definitely had started treatment in 2014. Now, treatment is accessible, but I don't feel strong desire to treat, due to issue of unknown cancer risks.

[Sergey]

'Curing Hepatitis C Offers Many Health Benefits To Those With Cirrhosis'.

Hi Andrew! I had read this article, but, firstly, this article speaks about interferon-based treatment (in 2006-2012), not DAA-based.  Secondly, this is not randomized trial - hence, results may be biased. Patients with less advanced, beginning cirrhosis are more likely to achieve SVR with interferon-based treatment, than with more advanced disease. Study shows association between SVR and better prognosis, reduced risks of health problems, but association does not mean causative relation. People with beginning cirrhosis are more likely to have better prognosis (than people with more advanced cirrhosis) even without treatment.

[Sergey]

Eric, of course, HCV may lead to death and many people dies from HCV-related cirrhosis. From the other side, I know one man, his cirrhosis was very beginning (possibly, more beginning than mine). No symptoms, no varices, no ascites, normal platelets. He started DAA treatment and relapsed. Several months after, AFP started to rise, and he was diagnosed with HCC. Tumor was resected but after that HCC recidive occurs. He was successfully transplanted  several months ago and now his AFP rises. Hope he will survive this quest, but I don't think that DAA treatment gave many benefits in his case... Now, probably, he has resistant HCV and may unintentionally infect others with DAA-resisntant HCV, which may be much more difficult to treat than "ordinary HCV".

For me, from point of view of evidence, treatment with lacking of good medical evidence (as described there - http://www.openhealthnews.com/story/2015-01-18/lack-good-medical-evidence-new-100000-hepatitis-c-drug-treatments) looks like being at some degree as "guinea pig", or participant of clinical trial - even without discussion about posttreatment cancer risks. With question about posttreatment cancer risks situation becomes more serious.

Of course, intention of saving other people from risk of HCV infection by our own treatment is compassionate, but as a result of possibly relapse - we may create more serious risks of spreading DAA-resistant HCV.

With best wishes,
Sergey.

[Sergey]

I guess figures are needed in order to weigh the relative risk factors of acquiring HCC pre, post, and absent DAA treatment among those with and without cirrhosis for all the various populations involved.  Without that I would think that treating is better than not treating, but without data to back this up, its only my individual bias which leads me to that conclusion.  Id much rather have data to look at that is dispositive  of the issue.

Yes, further studies are required. Recently, European regulator tells to pharma companies to perform such studies, but results may be available in 2021.

[kimlav]

Hi Sergey,

I can see you treated with the old interferon treatment which I was never going to try and yet you are afraid of 8 or 12 weeks of Harvoni, which was a walk in the park for me and for most others.

It is my understanding that those with cirrhosis etc. have a greater risk of HCC so the longer you let the HCV eat at your liver, the higher your chances will be of developing what you are fearing.

True freedom is never being infectious to anyone ever again.

 In addition, I will say that many of us did engage in risky behaviour that caused this disease and it is a no brainer for me that if I was adventurous enough to stick a needle in my arm, that I might just take a jump and go with treatment that I am unsure of - I mean we didn't even really know what was in our drugs and we do know what is in the DAAs. Just sayin....

Kim

[Lynn K]

Hi

After I was diagnosed with cirrhosis the new treatment inciveck was approved a few months later. I asked my doctor about beginning treatment with inciveck and was told with my prior treatment history and with having cirrhosis my odds of being cured were about 14% and the odds that the treatment could cause me to become decompensated were too high. I asked to see a different doctor for a second opinion who also said no too dangerous for me to treat.

I only had early cirrhosis at the time.

My point being even though I knew I had only a small chance of the meds working and a much greater chance of being harmed by treatment I still fought to get treated before I became very sick from liver disease. I was left with no options but to wait to die.

In the present situation even had there been some discussion about a very small chance that maybe there is an increased risk of HCC but odds were very high for a cure I would jump at the chance to treat. When I treated with Sovaldi and Olysio the meds had only been approved for 3 months. I failed that treatment by relapse. I next treated with Harvoni for 24 weeks starting treatment one month after its approval. So I was exposed to DAA's for a total if 36 weeks. Two years cured now no HCC.

Anyway as has been said it is your choice but for me not treating especially as you have cirrhosis is not a good option.

[andrew j]

Hi Sergey,

Just a minor correction:
It looks as though some of the people in that cohort did get DAAs (acknowledging that, given the study period, most probably got interferon-based Txs).

Something else:
Maybe there are new approaches to Tx being researched - no doubt there are - but
surely, without more [adverse indications], DAAs are likely to be the only available Tx for the foreseeable future?
... Which means that you may be waiting for a Tx (or some definitive research), for who knows how long?

No doubt you are aware of that risk.

(Maybe there is some way of combining DAAs with an agent that can dampen down their action a bit for certain patient groups?) ...

[Sergey]

Hi Kim!

Yes, interferon treatment has many side effects and, in average, seems much less pleasant than Harvoni. But it may be more safe regarding to cancer risks. I don't know studies about increasing of cancer risks after interferon treatment, but new reports about possibility of increased cancer risks after DAA treatment appear every several months. One of reasons for peg-rib treatment in 2005 in my case was that big harm to health was unlikely, despite many side effects like flu-like syndrom, tiredness etc. Really, I am not sure - whether  cancer risk bigger with positive HCV PCR or after DAA-treatment, due to contradictory results of modern studies.

I never trying intravenous drugs and was infected probably by blood transfusions in big surgery in 1977.

[Sergey]

Lynn, yes, I declined treatment with telaprevir due to similar reasons. I see, you had low platelets in 2014, before Harvoni. It may were a sign of not very beginning cirrhosis. You did not have cirrhosis at the time of HCV diagnosis - so, it seems, HCV was progressing without treatment in your case. Hence, attempt of treatment was well justified. In my case, generally, situation is not worse than 12 years ago, at the time of HCV diagnosis - and I am not sure that liver damage is progressing. Some studies report 5-7% of HCC risk in first post treatment year - it seems not very low for me. Time will tell, if liver function will get worse, hope it will be no problem to start treatment at any moment.

[Sergey]

Hi Andrew!

Yes, thanks, some people were treated with DAAs is this study. But, majority of people were treated with interferon.

Just as guess - DAAs will be mainstream of HCV treatment during next several years, and, of course, new drugs may be developed. Or, combiniation with other drugs may be used in future for some cases - for example, DAAs + interferon. It will be interesting, if HCV vaccine will be developed.

[Lynn K]

Yes when telaprevir was approved I did have cirrhosis but just to clarify I did not decline treatment I fought to be treated even though the odds of success were low and the risks were high.

At that time in 2008  I had just been diagnosed with cirrhosis and I was considered early cirrhosis with no reduction in platelet count. 

My doctor denied me treatment. I went for a second opinion at the University of WA in Seattle in attempt to be allowed to treat however the doctor there concurred with my gastroenterologist that the risk was too high even with just diagnosed early cirrhosis.

Had I been allowed I would have treated.

Yes when I was initially diagnosed with hep c in 1990 shortly after I think 1993 I had my first liver biopsy and was F1. Second liver biopsy in 1998 my result was F2. In 2003 I had my 3rd liver biopsy and my score was F3. Finally on my last liver biopsy in Jan 2008 my score was F4 early cirrhosis. I treated 3 times over those years with interferon based treatment including one clinical trial. My first treatment was interferon mono therapy with 3 shots a week as ribavirin had not yet been used for hep c treatment. So my liver disease was advancing even though I had done several treatments.

Just to add my liver enzyme tests were fairly consistent during my 23 years of known infection at just slightly above normal levels. Liver enzyme tests are not a good indication of advancing liver damage all liver enzyme tests indicate is something is harming your liver not how much damage you may have. You can have normal liver enzyme tests and have signifigant liver damage as I do now I have normal liver enzymes but cirrhosis. Or you can have high liver enzymes and no liver damage.

If you want to run the risk of advancing liver disease instead of treating now that is your option but personally I don't feel further waiting for more data is a wise choice.

[Sergey]

Lynn, yes, I understand your point of view and intention to treat. If it is clear that fibrosis (or cirrhosis) is progressing - then, we are usually tend to try treatment. If it  is not clear - whether it progresses or not - then situation may be not so obvious. I feel that HCV may have relatively benign course for many people, without fibrosis progression   (or even with regression of fibrosis) without antiviral treatment - in situations with healthy lifestyle (no alcohol, no overweight) and without big risks of rapid decompensation (no varices, no ascites, no symptoms, normal platelets). Each case is individual - one may progress rapidly, and other may not progress during many years - it may be difficult to predict... And I am planning to try to lose some body weight - hope it will help. Of course, normal transaminases do not guarantee absence of fibrosis/cirrhosis progression. Also, SVR is not 100% guarantee for absence of cirrhosis progressing - I know two guys, they are were transplanted despite SVR, but both had advanced decompensated cirrhosis before treatment - with big ascites etc. With compensated cirrhosis, it seems, SVR significantly reduces (or eliminates) risk of progression, but some low probability of decompensation may remain in some cases. With decompensated cirrhosis, situation may be much more difficult and SVR may not prevent liver transplantation in future (analysis of risks and benefits is needed)... I hope we will not progress to decompensated cirrhosis or HCC.

With best wishes,
Sergey

[Lynn K]

Hi Sergey

I guess I feel a little frustrated on your question you ask to treat or not to treat but is seems although many have suggested you to treat you are firmly leaning not to do so at least not at this time so I guess I feel like you already had your decision before you ever posed the question.

I am just one to try to fix a problem. I treated as an F1 back in the days of interferon. I am sure you heard how difficult that was. I treated with that stuff not once but 3 times I treated with unproven meds in a clinical trial to try to rid myself of hep c before it could cause additional damage but all that was without any success.

Anyway I am sure you can see from my perspective how I have a hard time understanding why you would not treat with the odds of cure so great the risks relatively low of treating vs the risks of not treating. Apparently we just don't view your situation remotely in the same way.

In any event  I wish you well and I hope your decision works out for you.

In health,
Lynn

[Sergey]

Hi Lynn!

No, I did not have decision before posting, and I am trying to monitor new publications about post treatment cancer risks. Since such publications are continuing to appear every several months - my doubts are rising. Also, lab tests, fibroscan and consultations with hepatologists are planned - and I will decide after that, dependent on results - in near months.

You treatment history is impressive, and I fully understand your reasons for treatment and participating in clinical trials. Please do not feel frustrated - probably, I am just a bit more conservative.

[dragonslayer]

Hi Lynn!

You treatment history is impressive, and I fully understand your reasons for treatment and participating in clinical trials. Please do not feel frustrated - probably, I am just a bit more conservative.

Sergey, I have to agree with Lynn.  You say you're a bit more 'conservative' but wouldnt the conservative approach be the one that favors treatment?   Numbers would show that the risky strategy is the one youve chosen.

I know that everybody here is in your corner, and as a result, many of us are afraid of the course youve chosen.. From all I know, cirrhosis can decompensate  suddenly and unpredictably.  What a horrible thing it would be for you if this were to occur, especially in light of the fact that your odds of being cured now are very high.

Weighing this against a possible HCC diagnosis down the road the odds of which are slim compared to getting cured now and lessening that chance as a result, wouldnt the surer, more conservative approach favor treatment now?

[gnatcatcher]

Waiting for inner clarity makes sense to me, Sergey. No one on this forum thread has walked in exactly the same shoes as you. From my experience with a different major diagnosis twenty years ago, I had an image of standing in front of two closed doors, each of which hid a horrible future outcome for a certain percentage of patients, and it was up to me to choose to open one of the two doors. You'll know inside yourself when it is time to decide. Here's hoping that you can feel, despite our limited ability to help, that we are all wishing you the best possible outcome.

Gnatty

Sergey, I can't say it better now than I did in November. I'm glad you'll be getting lab tests, fibroscan, and consultations with hepatologists soon -- that should help you come to a resolution. Best wishes. -Gnatty

[Mugwump]

Yes there does seem to be some evidence that DAA treatments are exposing more who go on to develop HCC. HOWEVER this may very well only be the exposing of individuals who were on the way to developing HCC in the first place not an increase in treatment complications risks.

I do not think that the older interferon treatments had less any less risk of exposing the individuals who were prone to developing HCC, the reason for this is that the type of interferon used is not effective in treating HCC or been shown to lessen the risks of HCC.

For now the evidence only shows that the increase in HCC cases during and post treatment is happening solely because for the first time we are seeing the majority of stage F4 cases being cured.

Simply put Sergey, the evidence would still seem to indicate that the longer you wait the greater your risk of developing HCC or the other deadly complications of cirrhosis regardless of the method of treatment.

If there was a way of determining and mitigating the risk for those among us are more prone to developing HCC, it would be a God send. But for now we have to take what we have been given with HCC being a complication that many have suffered and many will still suffer because of the nature of HCV infection and the ongoing set of complications it brings.

Anyway the ice is off the lakes and it is time to give some fish sore lips for this cowboy!!

All the best Sergey.
Eric

[Sergey]

Hi Paul!

From all I know, cirrhosis can decompensate  suddenly and unpredictably.  What a horrible thing it would be for you if this were to occur, especially in light of the fact that your odds of being cured now are very high.

From compensated asymptomatic beginning cirrhosis, without varices, without ascites, with normal platelets and relatively low MELD - sudden fast decompensation is unlikely. Usually, progression of cirrhosis from such state is a process of gradual worsening of liver function during many years - platelets becoming lower year by year, fibroscan values are rising etc. This does not mean that progression will definitely occur without treatment, situation may be stable (in my case, situation is stable during 12 years). Cirrhosis may have different causes - for example, excessive alcohol consumption in the past, and if such patient will abstain from alcohol - then it may not progress further despite HCV

Weighing this against a possible HCC diagnosis down the road the odds of which are slim compared to getting cured now and lessening that chance as a result, wouldnt the surer, more conservative approach favor treatment now?

This is a question of weighting up benefits and risks. In short term (1-2 years) - what will I have after successful treatment? I will have beautiful sheet of paper, lab report with word "undetected", with normal ALT and AST. Well, it is beneficial psychologically. And what is price for it? Possible price may be 5-7% in a year risk of getting cancer. Is it worth to buy nice sheet of paper by price of possible 5-7% in year risk of cancer? In my opinion, it is controversial.

In long term, of course, in worst case scenario, cirrhosis may decompensate. Treatment may prevent decompensation - and if cirrhosis was clearly progressed - (as it was in Lynn's situation, for example) - treatment may be well justified. Just because without treatment, such situations may lead to decompensation within several years. From the other side, potential possibility of increased post treatment cancer risks exists. In a stable situation (like mine), it is difficult to predict long-term benefits and risks - just because these drugs are relatively new and long term studies are absent. For example, possible increased posttreatment cancer risks may outweigh probability of decompensation.

So, these drugs are bit experimental and not well studied. "Conservative" strategy for me implies avoiding of using of possibly carcinogenic not well studied drugs (and clinical trials with such drugs) without strong reason for treatment, in stable asymptomatic state.

[Sergey]

Gnatty, thanks. Yes, situation is not changed much from November.

[Sergey]

Hi Eric!

HOWEVER this may very well only be the exposing of individuals who were on the way to developing HCC in the first place not an increase in treatment complications risks.

IMHO, it looks like assumption. It may be correct, or it may be wrong - it is difficult to say. It may be dependent on some genetic features of immune system, for example.

For now the evidence only shows that the increase in HCC cases during and post treatment is happening solely because for the first time we are seeing the majority of stage F4 cases being cured.

No, I don't think so.  In some studies cited above - there is unusually high probability of HCC (and, in some studies, unusual aggressive HCC pattern) among cirrhotics after treatment. If some distortion of immune system occurs, due to rapid suppression of HCV by DAAs - just as guess, potentially, people without cirrhosis may be affected too.

Happy fishing to you!

With warm wishes,
Sergey

[I fightis thetitis]

Hey Sergey,

Either way, no matter which decision we make we play roulette.
The ONLY difference is based on current avail statistics, your odds to not treat are not in your favor.

As you know even though your numbers are stable right now, obviously that could change in a month, week or even while exercising if you have varicies.

Just as you could be at a higher risk for HCC through DAA treatment.
Although, it does appear the needle is moving away from that.
Current evidence of a smoking gun at best can only be "worrisome" not confirmed.

The only confirmation is if you don't treat, eventually you will get a direct or indirect HE condition due to the unchecked virus.

I wish you well and respect your decision even though it differs from what I would do.
I look forward and hopeful I'm around to witness how DAA treatment unfolds for all of us F4's.

Best always,

Greg

[Sergey]

Hi  Greg,

Yes, we play roulette. Evidence about higher risk for posttreatment HCC is "worrisome", not confirmed, yes. Or, in other words - drugs are "possibly carcinogenic", not "probably", and not "definitely" - possibly, "maybe yes, maybe no" - difficult to say.

While the situation is stable (and not worse than 12 years ago) - I believe that odds is in my favor and rapid decompensation is unlikely without treatment.  I guess, varices are absent. Of course, if liver function or ultrasound, fibroscan etc. will become worse - then at some point I am planning to start treatment.

Thanks and best wishes,
Sergey

[dragonslayer]

While the situation is stable (and not worse than 12 years ago) - I believe that odds is in my favor and rapid decompensation is unlikely without treatment.  I guess, varices are absent. Of course, if liver function or ultrasound, fibroscan etc. will become worse - then at some point I am planning to start treatment.

Thanks and best wishes,
Sergey

But shouldnt this be a prime consideration?  Your disease has already progressed to cirrhosis.  The more fibrotic your liver becomes via progression, the less likely will be your chance of significant regeneration after a cure.  Just check with Lynn.   In addition, as I know you know,  the cirrhotic liver has its own increased HCC risks.

Many of us wish you would change your mind because we believe it will be your  best chance at a better life,  but I also know you have to come to grips with whatever path you choose. We're just trying to point you in another direction.

I also want to ask you, do you experience no extra hepatic manifestations?  Sometimes its hard to realize you are until you no longer have the disease.. Little weird symptoms that crop up over time are often ignored until theyre not there anymore.

At any rate, Sergey, all the best to you, and I know youll be keeping us up to date... Hope your decision works for you.  Its a really tough one to make.  There are clearly pluses and minuses on each argument.  BTW,  Isnt the HCC risk much higher in the case of recurrence rather than as a denovo development?

[Lynn K]

Yes as Paul said my Fibroscan was 27 before treatment and 33 one year post. I didn't have it checked at 2 years post. The only positive sign was my platelet count rise from pre treatment levels of 90 to now 110.

Also my NP at the liver center has concerns that even though I am cured my cirrhosis could continue to progress because I have had it for so long. I am changing my care to the University of Washington now to see about a better opinion on that. They are involved in many studies you likely have read some from them.

Wishing you the best

[Gaj]

Hi all,

Here is a very recent summary on the HCC situation as currently understood. As they note, further study is required but the overview of all the studies does not seem to indicate a significant risk increase for the majority of patients.

"Though the data is limited to these studies as we are just now seeing long-term implications of DAAs, the frequency of HCC recurrence after DAA therapy is still controversial. We require larger studies but the existing evidence does not support the withholding of antiviral therapy from patients with HCV even with a history of HCC."

http://www.healio.com/hepatology/oncology/news/print/hcv-next/%7Be4dcf746-1ebf-49b6-9f3c-5088873dc0cb%7D/hcc-after-daas-requires-more-study-but-no-cause-for-withheld-treatment

[Lynn K]

This looks like it is about recurrence of HCC in patients previously treated for liver cancer.

I believe Sergey is primarily concerned with the risks of new HCC diagnosis in patients after treatment with DAA's who were not previously diagnosed with HCC before they treated.

[Gaj]

Hi Lynn,

Partly, and that is to be expected as much focus in the discussion on this topic is regarding recurrence which is where most of the reports of higher than expected rates come from but would point to P3, second paragraph of the link that I have quoted below regarding the de novo situation.

"With regard to de novo HCC post-SVR, there remains incontrovertible evidence for a major reduction in de novo HCC risk after SVR. There is no convincing evidence for a transient “spike” in de novo HCC post-SVR with DAAs, but the question of an alteration in the biology of de novo HCC after SVR requires further study."

I hope that at some point Sergey will be confident enough of the evidence to make his own decision regarding his best course of action, whichever way he decides. But I also posted this because there will be other readers, both with and without HCC history, who are worried and may find the link useful in providing further information.

[Lynn K]

Hi Gaj

Good point about others who may later read this thread. I believe Sergey is concerned about de novo infection because there is data on both sides of that issue.

However, it will likely be many years if ever this question is totally resolved. In my thinking the risk of de novo HCC is low and the risk in general for someone with longstanding liver cirrhosis is much greater.

But it seems Sergey has his concerns and remains undecided which for him is the better option. Whether to risk the debated concern of possible risk of de novo HCC post treatment or run the risk of either future decompensation or HCC due to having liver cirrhosis. Bearing in mind the risk of HCC for those with cirrhosis and HCV is reduced with cure of HCV.

[I fightis thetitis]

I echo what Gaj said.. and regarding this sentence from his post...

""With regard to de novo (NEW) HCC post-SVR, there remains incontrovertible (irrefutable) evidence for a major reduction in de novo (NEW) HCC risk after SVR."

I believe the key word for anyone considering treatment is "incontrovertible"
I wish they would have just said "irrefutable" ..same thing but somehow seems more powerful.

Best to you all!

[strangerbynight]

After reading these post i am now paranoid from my ultralsound and CT scan reports that i have a small cyst and hemangioma, i just hope the tech and the equipments are reliable and no errors, but my fibroscan is F0-1, should i be concern? i am about to take generics harvoni in about a week..

[Lynn K]

Cysts and hemangiomas are not uncommon and are benign. Nothing to worry about.
HCC  (Heptocellular carcinoma) is only a risk for those with F4 cirrhosis.