TOPIC:

If i correctly understand, some studies show that fibrosis may be reduced in proportion of patients without antiviral treatment:

1. Body weight reduction programm may reduce fibrosis in 3 month - www.ncbi.nlm.nih.gov/pmc/articles/PMC1773265/
Fibrosis was reduced in 5 of 10 patients:

2. Possibly, fibrosis may be reduced spontaneously:
www.cghjournal.org/article/S1542-3565(06)00497-6/fulltext - in a follow-up study, 24% of patients showed regression of fibrosis
www.gastrojournal.org/article/S0016-5085(03)50023-3/fulltext - in another study, also 24% of patients showed improvement of fibrosis

Hi Serg,

my opinion is that there might be couple of tricks to help the liver stay in a good shape and slightly reduce fibrosis, however if the virus is not eradicated, it will continue to produce damage.
I also fear that the damage being produced is not linear, e.g. if this year you feel your energy drop is 5% by compare with last year, this does not imply that next year your energy will decrease with another 5%.
I am not an expert in medical sciences, but I believe that the more liver damage is being produced, the faster the health deteriorates.

So, my advice to any HCV patient is: if there is a chance to get treated, TAKE IT! (and also read further the short text from my signature GENERICS WORK !!!)

Cheers,
RHF

Reducing 10 lbs is one of the strategies we used with the old interferon treatment because it reduced insulin resistance and that increased SVR...sometimes.

P.

Price wrote: Reducing 10 lbs is one of the strategies we used with the old interferon treatment because it reduced insulin resistance and that increased SVR...sometimes.

P.

The meds helped me further lose weight as I had more energy/will to exercise more and then eat less when the weight started dropping (ever so slowly).

Jeff

Hi rohcvfighter, good luck with your therapy!

Yes, very good news is that, it seems, GENERICS WORK and generics are relatively cheap. I am planning to start sof/led/rib or sof/dac/rib therapy in this year, due to F4.

Yes, we dont know fully, how fibrosis will progress with HCV in each particular case, especially in eldery (or it will be unchanged for decades or it will even regress/improve in some percent of patients). Areas of "HCV infection" and "treatment of HCV infection" seems still not very well studied... If i correctly understand, best available data suggests that only minority (20% or like that) of infected people will need a liver transplant or will die from hepatic-related causes if HCV infection will left untreated. But these data are usually collected from groups of relatively young people, often with good predictors. Prognosis may be more poor for people with "bad" predictors.

From the other side, some studies show that virus persists for many years after SVR in majority of people, detected by special ultrasensitive equipment - www.ncbi.nlm.nih.gov/pmc/articles/PMC415836/ , onlinelibrary.wiley.com/doi/10.1002/hep.20518/full Is it possible that "eradication of virus due to treatment" - is one of Big Pharma's "marketing slogans", which is not supported well by "scientific" data? :)

Also, there is a lack of good medical evidence about hcv treatment - www.openhealthnews.com/story/2015-01-18/...is-c-drug-treatments In my opinion, lack of good medical evidence - is important point. This means that hcv treatment, if i correctly understand, is at some degree "experimental" treatment, or like "clinical trial" at some degree.

Some adverse events are possible during HCV treatment. Recently, on rissian-spoken forum we read about onset of ECG abnormalities and some sort of cardiac arrhythmia during sof-dac-rib treatment. Will arrhythmia disappear with cessation of HCV treatment or not? If not, whether long-term risks from carrying HCV with F0-F1 will outweigh long-term heart-related risks from arrhythmia? I am not sure. Some people with sub/decompensated cirrhosis suffer from further decompensation due to treatment, despite SVR. Unsuccessful treatment attempts may lead to developing of resistance which may complicate further retreatment...

Due to such things, currently, i am not a big enthusiast of recommending "to undergo HCV treatment" to everyone of infected... Obviously, all hcv-infected people should have easy access to modern hcv medications and should be well informed about generics, treatment and hcv-infection. But treatment decision ("to treat" or "not to treat" etc.), probably should be individualized, taking into account possible benefits and risks of each alternative, overall health, age, previous treatment attempts.

Best wishes,
Serg

Hi Serg,

thank yoy for the post and the links you provided. I understand your point of view and why you feel in this way.

I would like to emphasize one important point: the HCV is very tricky and the fact that there exist new and effective medication should not be understood that everyone will simply go to the pharmacy and buy it. Each patient has his/her own story therefore seeing and discussing with the doctor about the treatment is essential. The chance to get treated means in fact that the patient has recrived the right diagnosis, gets from the doctor the information about what treatment to take and ... can access the treatment. That's the chance that I recommend .

Just the information about medication is not enough, it is only a variable from the complex equation of getting treated from HCV.

Cheers,
RHF

From the other side, some studies show that virus persists for many years after SVR in majority of people, detected by special ultrasensitive equipment - www.ncbi.nlm.nih.gov/pmc/articles/PMC415836/ , onlinelibrary.wiley.com/doi/10.1002/hep.20518/full Is it possible that "eradication of virus due to treatment" - is one of Big Pharma's "marketing slogans", which is not supported well by "scientific" data?

Hi Serg,

Both the studies you list in the above quote are from 2004 and well prior to the development of modern DAAs such as Sofosbuvir, Ledipasvir, Daclatasvir, etc, etc. If you are going to cite studies to try to support your claims about the modern DAAs you need to provide more current information. The rest of your post provides no further evidence or support for any of your concerns either other than to quote Roy M. Poses MD, an outlier in the medical community who also presents all his "arguments" in terms of FUD (Fear, Uncertainty & Doubt).

With all new medications at some stage a decision has to be made whether to approve their use or not as has occurred for the DAAs via the FDA, European and other relevant authorities. As you appear to feel this approval has occurred too early, can you clarify at what point you would consider treatment to no longer be "experimental" or "clinical trial"? Is it a matter of years, or numbers of patients treated....how many of either or both? Or is there some other criteria that you believe should be used? Please keep in mind that even drugs like Aspirin and penicillin still have some side effects and risks despite having been used for over half a century.

However, I do agree with most of your statement that "treatment decision ("to treat" or "not to treat" etc.), probably should be individualized, taking into account possible benefits and risks of each alternative, overall health, age, previous treatment attempts."

Hi, Gaj!

I dont know about studies which show persistence of virus after SVR due to modern "DAA-only" therapy. But this does not mean that such persistence is impossible. In this article (www.hindawi.com/journals/grp/2015/579147/) there are some concerns:

With the shorter duration of therapy with the new DAA and in the absence of interferon that has the potential to induce an immunologic attack directed at the putative “protected reservoirs” of HCV, concern for an increased prevalence of OCI in the future as a result of treatment with DAA represents a worrisome possibility.

The currently widely held assumption of a HCV-cure in individuals having had “SVR” after 8–12 weeks of a course of DAA therapy as recently defined may not be entirely valid. Careful longitudinal followup utilizing highly sensitive assays and unique approaches to viral isolation are needed.

Gaj wrote: With all new medications at some stage a decision has to be made whether to approve their use or not as has
occurred for the DAAs via the FDA, European and other relevant authorities. As you appear to feel this
approval has occurred too early, can you clarify at what point you would consider treatment to no longer be
"experimental" or "clinical trial"? Is it a matter of years, or numbers of patients treated....how many of
either or both? Or is there some other criteria that you believe should be used?

If i correctly understand, this is relatively old discussion in "medical world", which was started before approving of modern DAAs, from times of interferon-based treatment (see, for example, www.journal-of-hepatology.eu/article/S01...(13)00598-9/fulltext - "Therefore, definite evidence for the clinical efficacy of interferon therapy was never established and SVR was never formally validated. The use of SVR as surrogate outcome measure thus remains with some uncertainty.") The problem lies in "slow progressing" nature of HCV-infection. According to priciples of evidence-based medicine, randomized controlled trials on "hard points" (such as death, liver transplantation etc.) must be performed to validate SVR as surrogate outcome. In other words, roughly speaking, we need to randomize many (for example, several thousands) patients to 2 groups, one group will receive treatment and other group will not receive treatment. If patients in first group (treated) will demonstrate statistically better survival, than in second (untreated) group, then we can say that treatment is effective in term of improving survival. But, due to "slow" nature of HCV infection, such trials are costly and will require many years of observation (or even decades for people with mild fibrosis). FDA, EMA etc. approved HCV medications without such trials, probably due to ethical reasons (otherwise, appearance of medication on market was delayed for many years). But, as a result, we have no complete evidence base from point of view of evidence-based medicine. Roy M.Poses points to this fact in his article. If i correctly understand, many world-known hepatologists (for example, authors of www.journal-of-hepatology.eu/article/S01...(13)00598-9/fulltext) agreed with this fact (so, this is not only "my" point of view). Yes, Roy M.Poses may seems as "outlier in the medical community"... But, anyway, this not affects the fact of absence of required (from point of view of evidence based medicine) trials. Also, is it possible that Big Pharma may "pressure" medical community, guideline makers etc. - to "suppress" such voices like Dr.Poses, for promoting treatment and for maximizing profit from selling drugs?

P.S. Some information about Roy M.Poses, his background, awards and honors - vivo.brown.edu/display/rposesmd Really, i dont think that he is outlier in the medical world.

Hi Serg,

"Evidence based medicine" is indeed a worthy and appropriate goal and I would suggest is largely what the majority of the modern medical profession aspires to using.

The problem comes when people start to say that it is the one and only true path and that we should not proceed until we have every last bit of evidence. There also seems to be a misguided implication that all the evidence must be positive to proceed. If we were to take that approach to my earlier example of penicillin then I would guess we would be able to make a decision whether it was safe and appropriate to use sometime in the not to distant future, and the answer would likely be NO! Which would be bad for all those people who's lives and limbs it has saved over the last seventy something years.

As we are all individuals who to some extent react differently to both disease and treatment, total reliance on EBM is likely to lead to paralysis of the medical system. To avoid that dilemma, as with just about every human endeavour, we often need to make a decision based on the balance of probabilities. An educated guess if you will?

I do understand your concerns and commend your research but keep in mind that if you search long enough on the internet you will always be able to find someone with an opposite view. When that happens you need to decide which way to proceed based on the weight of evidence plus your experience and confidence in the alternate arguments presented.

As for Poses, I believe he does provide a valuable service in questioning the status quo and reminding us that the business, medical and political establishments need to be watched to ensure that their actions are not driven purely by self interest. He also appears to be a strong advocate for EBM but I detect a level of fundamentalism in his advocacy that suggests that he is operating outside of the 'real world' of people's ongoing health and lives while at the same time appealing to their insecurities. In other words he is more interested in the principle than the people it effects as per his bulletpoint comments below from the article you cited.

The best evidence available suggests that most patients with hepatitis C will not go on to have severe complications of the disease (cirrhosis, liver failure, liver cancer), and hence could not benefit much from treatment.

I agree with the opening part of his statement, not so much with his conclusion which appears to argue that we should ignore anything that isn't a "severe complication" to our health. Are we to apply the same rules to areas of health outside of HCV? Is he suggesting that patients with hypertension could not benefit much from treatment because it doesn't always result in strokes, aneurysms or cardiac events?

There is no evidence from randomized controlled trials that treatment prevents most of these severe complications

Correct! Clinical approval trials were to prove safety and efficacy in achieving SVR. To undertake "randomized, controlled trials" to provide that sort of evidence for the "severe complications" would probably take decades as you note yourself. However, there are now a considerable number of retrospective studies that are showing that achieving SVR results in less risk of progression along the path to those more severe problems than non treatment.

There is no clear evidence that "sustained virologic response," (SVR), the surrogate outcome measure promoted by the pharmaceutical industry, means cure. 

True dat! It is why it is called SVR and not CURE. We do however have evidence that achieving SVR12 gives about a 99% chance of no relapse over the period that we have been able to study so far and retrospective studies appear to show benefits associated with that.

While the new drugs are advertised as having fewer adverse effects than older drugs, it is not clear that their benefits, whatever they may be, outweigh their harms.

Oh, this is just a classic fear mongering statement. It is designed to scare rather that elucidate or educate and rates number one out of his four statements as justification for my calling him out for use of FUD tactics.

Hi, Gaj!

Gaj wrote: The problem comes when people start to say that it is the one and only true path and that we should not proceed until we have every last bit of evidence.

Yes, I agree. There are situations, in which it will be very hard to obtain complete evidence. Speaking "formally", from point of view of EBM, we should start "prescription" treatment only after having of "complete evidence" from trials. Obviously, it may be unethical - for example, if required trials may require decades. But, i believe that patients should be informed about such situations, in which treatment is initiated without having of full evidence base, because this fact may affect treatment decision.

Gaj wrote: There also seems to be a misguided implication that all the evidence must be positive to proceed. If we were to take that approach to my earlier example of penicillin then I would guess we would be able to make a decision whether it was safe and appropriate to use sometime in the not to distant future, and the answer would likely be NO!

In terms of having adverse events, not all evidence must be positive, according to EBM. For example, many drugs have serious adverse events, they are not safe, and, at the same time, they have good medical evidence. Key point is that drug must demonastrate their effectiveness in randomized trials on relevant "solid clinical endpoint". For example, for treatment of pneumonia with penicillin, randomized controlled trial will show significantly improved survival in group of treated compared to group of untreated. But penicillin have adverse events (as almost every medication) - and some people may die from allergic reaction caused by penicillin, for example. But, when it is decided to take penicillin, patient will be sure that, based on trials, there are good evidence that overall probability to improve survival is much more than probability "to worse" survival. In other word, on the average, "benefits outweigh harm" or "drug do more good than harm". Other possible example - many serious anticancer drugs have good medical evidence (based on randomized trials, these drugs, on the average, improve survival) but they have serious adverse events also.

Gaj wrote: As we are all individuals who to some extent react differently to both disease and treatment, total reliance on EBM is likely to lead to paralysis of the medical system.

Generally, I dont think like this. Usually, it is possible to perform clinical trials according to EBM principles. Such situation as with HCV treatment - seems as "exception rather than the rule".

Gaj wrote: I agree with the opening part of his statement, not so much with his conclusion which appears to argue that we should ignore anything that isn't a "severe complication" to our health. Are we to apply the same rules to areas of health outside of HCV? Is he suggesting that patients with hypertension could not benefit much from treatment because it doesn't always result in strokes, aneurysms or cardiac events?

Probably, his point was - to percieve this argument together with available "evidence base" about treatment. For example, in situation when every infected with some disease will definitely die within 5 years without treatment, applying of some experimental treatment is justified (in situation of absence of other alternatives). But, if only 10-20% will die from disease without treatment during lifetime - applying of experimental treatment may seems questionable. Antihypertensive drugs usually have good evidence in preventing strokes etc., hence, they are not experimental treatment.

Gaj wrote: Oh, this is just a classic fear mongering statement. It is designed to scare rather that elucidate or educate and rates number one out of his four statements as justification for my calling him out for use of FUD tactics.

This statement is a consequence of fact of absence of required trials, according to EBM. He seems as enthusiast of EBM, and, i think, he tries to inform people in "simple words" about such things. But, these things, by their nature, may seems quite scary and, hence, psychologically, it may be difficult to accept them... Personally, i am not very easy accepted these things several years ago.

Best wishes,
Serg.

Hi Serg

Thanks for your verbose and entertaining posts in which you argue yourself into a loose granny knot about the need for long-term EBM over “ … many years of observation (or even decades for people with mild fibrosis)” before HCV DAAs can be an ethically approved treatment according to your strict interpretation of EBM.

Gaj has easily untied your loose granny knot arguments and exposed then for what they are. There’s nothing further that needs to be added except for a truism attributed to John Maynard Keynes:

“In the long-run, we’re all dead.”

Thank god that what you espouse is not followed, as most of us on this forum would not be alive in the “decades” time, that are needed according to your strict EBM criteria, to ethically approve the currently FDA approved HCV DAAs.

The only medically unethical thing about the currently FDA approved HCV DAAs is the abhorrent abuse of patent laws used by big pharma to charge exorbitant monopoly prices for them. You are better advised to take up your arguments with the patent holders.

Hi, GT2!

Firstly, I am sorry for my posting about such "cold facts" - definitely, it may be psychologically difficult to accept these things for many people. Also, I believe that, mainly, these are not "my" arguments, or "my" "strict interpretation of EBM" - these are arguments/interpretetion of several famous medical experts (Roy M Poses etc.). And, probably, you may argue with Dr.Poses, if you feel that he is wrong in his interpretation of EBM, for example. Also, I never wrote that "modern DAA treatment must be stopped as ethically unapproved " - please do not attribute to me such thoughts.

You are better advised to take up your arguments with the patent holders.

My voice has not weight at all. But, possibly, we have cheap generics available, also, due to such articles from medical experts about lacking of good medical evidence. This is one of arguments for pressuring of patents holders for reducing price of HCV medications.

Whoops!

Hi Serg,

No need to apologise. You presented your case, I presented mine and.....um.....GT2 presented his.

Anyway, I guess we'll just have to agree to disagree about to what level we take EBM before patients can be treated with reasonable confidence. I am glad to see that you as a F4 are considering starting treatment this year though, that is not a decision that should be put off indefinitely.

And while you are only one voice, never think that it carries no weight at all. The sound of many such voices combined travels a long way.