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I can be positive with TTW or hepatitis G viruses by PCR test, for example. But this does not mean that i have a “disease”, because such viruses will not cause symptoms for me (like cirrhosis). Analogically, if HCV will not cause symptoms for me – what is the reason to define such situation as a “disease”? Of course, for such proportion of patients, who will develop cirrhosis/extrahepatic manifestations during lifetime – HCV is a disease. But many infected people will not develop symptoms.
Probably infected in 1977
2005 – diagnosed with HCV 1b, compensated F4, 15 mln viral load, ALT 320
2005-2006 – PegIFN/rib 48 weeks treatment, relapse
2016 – compensated F4, MELD 8-9, ALT 100-160
2018 – compensated F4, MELD 8, ALT 91P.S. I agree with your statements – “cirrhosis/extrahepatitic manifestations are symptoms”, and “it is possible to have a disease without displaying obvious symptoms”.
Probably infected in 1977
2005 – diagnosed with HCV 1b, compensated F4, 15 mln viral load, ALT 320
2005-2006 – PegIFN/rib 48 weeks treatment, relapse
2016 – compensated F4, MELD 8-9, ALT 100-160
2018 – compensated F4, MELD 8, ALT 91I disagree. If i correctly understand, term “disease” implies, that there are symptoms of disease or these symptoms will definitely occur in future. If there are no symptoms and symptoms will not occur in future, during lifetime – what is the reason to define this situation as a “disease”?
Probably infected in 1977
2005 – diagnosed with HCV 1b, compensated F4, 15 mln viral load, ALT 320
2005-2006 – PegIFN/rib 48 weeks treatment, relapse
2016 – compensated F4, MELD 8-9, ALT 100-160
2018 – compensated F4, MELD 8, ALT 91If i correctly understand, it may be possible another interesting thing with semantics. If majority of HCV-infected people will not develop cirrhosis and complications of cirrhosis, extrahepatic manifestations during lifetime without treatment – then, HCV infection is not a “disease” for these majority of people. Hence, really, they are “healthy” people, despite they are infected. The “treatment”, for many people, really, is “prophylaxis” of “diseases” (cirrhosis/extrahepatic manifestation) in a “healthy” person.
Probably infected in 1977
2005 – diagnosed with HCV 1b, compensated F4, 15 mln viral load, ALT 320
2005-2006 – PegIFN/rib 48 weeks treatment, relapse
2016 – compensated F4, MELD 8-9, ALT 100-160
2018 – compensated F4, MELD 8, ALT 91Hi, rohcvfighter!
“cure” implies that the virus is gone and the liver returns to the normal status (no fibrosis).
Yes, often “cure” implies that the virus is gone completely. But normal status of liver is “no cirrhosis”. Liver fibrosis itself is not a disease, and many healthy people have liver fibrosis without history of having hepatitis virus. Really, we cannot be completely sure that “virus is gone completely”, because we cannot exclude possibility of “occult” hepatitis, which is not detected by current conventional PCR blood test.
No matter whether we talk about SVR or cure or whether some small HCV RNAs exists somewhere in small quantities, as long as there will be no more “destruction force” against the liver, I can live very fine with SVR12/SVR24,SVR48
“Occult” hepatitis due to small quantities of HCV RNAs is not well-studied – hence, we cannot be completely sure that such possible kind of hepatitis is not a “destructive force”… Also, damaging of liver, caused by HCV, does not depends on viral load. We may have low viral load (for example, 200 copies per ml) and fast fibrosis progression, or we may have 10 millions per ml and no fibrosis progression during many years. Hence, if we will have, for example, 0.5 copies per ml after SVR, which are not detected by current conventional PCR test – we cannot 100% confidently predict possibility/rate of fibrosis progression. In anyway, SVR looks like a good prognostic sign and i wish you to achieve SVR with your therapy!
Probably infected in 1977
2005 – diagnosed with HCV 1b, compensated F4, 15 mln viral load, ALT 320
2005-2006 – PegIFN/rib 48 weeks treatment, relapse
2016 – compensated F4, MELD 8-9, ALT 100-160
2018 – compensated F4, MELD 8, ALT 91Hi GT2!
I agree to respectively disagree with the likes of Roy M Poses about his extreme views on EBM.
I dont think that he has unusual “extreme” EBM views… His views looks like “standard” (but yes, strict) EBM views for me. Something like this: “New medication must prove its effectiveness in properly done randomized trials.If not, then we cannot be 100% sure whether benefits outweigh harm or not, whether drug do more good than harm or not.” According to EBM metodology, lacking of properly done randomized trials leads to uncertainty about effectiveness of drug.
Rather, HCV infection looks like extreme example of “slow progressing” condition. Such “slow” character of HCV infection seriosly complicates performing of randomized trials (which required according to EBM).
Really, Roy M Poses is not against HCV treatment “at all” in current situation, in his blog he wrote that treatment should be individualized.
I wish you the best in deciding on the appropriate HCV treatment for your circumstances based on an acceptable degree of confidence according to your criteria.
Thank you. I wish you to achieve SVR with your therapy.
Probably infected in 1977
2005 – diagnosed with HCV 1b, compensated F4, 15 mln viral load, ALT 320
2005-2006 – PegIFN/rib 48 weeks treatment, relapse
2016 – compensated F4, MELD 8-9, ALT 100-160
2018 – compensated F4, MELD 8, ALT 91Hi, Gaj!
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.
Thanks. Yes, agree, it seems, for me, it is better try to undergo modern treatment with compensated F4.
Probably infected in 1977
2005 – diagnosed with HCV 1b, compensated F4, 15 mln viral load, ALT 320
2005-2006 – PegIFN/rib 48 weeks treatment, relapse
2016 – compensated F4, MELD 8-9, ALT 100-160
2018 – compensated F4, MELD 8, ALT 91Hi, 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.
Probably infected in 1977
2005 – diagnosed with HCV 1b, compensated F4, 15 mln viral load, ALT 320
2005-2006 – PegIFN/rib 48 weeks treatment, relapse
2016 – compensated F4, MELD 8-9, ALT 100-160
2018 – compensated F4, MELD 8, ALT 91Hi, 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.
Probably infected in 1977
2005 – diagnosed with HCV 1b, compensated F4, 15 mln viral load, ALT 320
2005-2006 – PegIFN/rib 48 weeks treatment, relapse
2016 – compensated F4, MELD 8-9, ALT 100-160
2018 – compensated F4, MELD 8, ALT 91P.S. Some information about Roy M.Poses, his background, awards and honors – https://vivo.brown.edu/display/rposesmd Really, i dont think that he is outlier in the medical world.
Probably infected in 1977
2005 – diagnosed with HCV 1b, compensated F4, 15 mln viral load, ALT 320
2005-2006 – PegIFN/rib 48 weeks treatment, relapse
2016 – compensated F4, MELD 8-9, ALT 100-160
2018 – compensated F4, MELD 8, ALT 91Hi, 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 (http://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, http://www.journal-of-hepatology.eu/article/S0168-8278(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 http://www.journal-of-hepatology.eu/article/S0168-8278(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?
Probably infected in 1977
2005 – diagnosed with HCV 1b, compensated F4, 15 mln viral load, ALT 320
2005-2006 – PegIFN/rib 48 weeks treatment, relapse
2016 – compensated F4, MELD 8-9, ALT 100-160
2018 – compensated F4, MELD 8, ALT 9118 July 2016 at 11:26 am in reply to: Reduction of liver fibrosis without antiviral treatment #21024Hi 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 – http://www.ncbi.nlm.nih.gov/pmc/articles/PMC415836/ , http://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 – http://www.openhealthnews.com/story/2015-01-18/lack-good-medical-evidence-new-100000-hepatitis-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
Probably infected in 1977
2005 – diagnosed with HCV 1b, compensated F4, 15 mln viral load, ALT 320
2005-2006 – PegIFN/rib 48 weeks treatment, relapse
2016 – compensated F4, MELD 8-9, ALT 100-160
2018 – compensated F4, MELD 8, ALT 91Hi, Gaj, sorry to hear this… Probably, you had relatively strong NS5A resistance before starting of sof-dac therapy, due to previous exposition to dac during first peg-dac-rib therapy… Such resistance may cause relapse. I dont know about retreatment data with velpatasvir after 24 weeks of dac/led therapy. If you don’t have resistance to sofosbuvir, possibly peg-sof-rib may be an another option. Probably it is better to perform mutation testing before next therapy attempt.
P.S. Is lab error possible with “false positive” result?
Probably infected in 1977
2005 – diagnosed with HCV 1b, compensated F4, 15 mln viral load, ALT 320
2005-2006 – PegIFN/rib 48 weeks treatment, relapse
2016 – compensated F4, MELD 8-9, ALT 100-160
2018 – compensated F4, MELD 8, ALT 91Full text of study is available via sci-hub – http://link.springer.com.sci-hub.bz/article/10.1007%2Fs10620-005-3059-x#
Probably infected in 1977
2005 – diagnosed with HCV 1b, compensated F4, 15 mln viral load, ALT 320
2005-2006 – PegIFN/rib 48 weeks treatment, relapse
2016 – compensated F4, MELD 8-9, ALT 100-160
2018 – compensated F4, MELD 8, ALT 91If i correctly understand, symptomatic cryoglobulinemia (for example, cryoglobulinemic vasculitis with serious damaging of kidneys) due to HCV infection, usually, is an indication for rapid initiation of HCV treatment. Asymptomatic cryoglobulinemia often does not require treatment. Successful HCV treatment may lead to disappearance of cryoglobulinemia in majority of patients. From the other hand, there are some data, that successful HCV treatment itself may cause cryoglobulinemia:
Before treatment, cryoglobulins were detected in 25 subjects (50%). Only 1 of the 25 patients with asymptomatic mixed cryoglobulinemia had persistence of cryoglobulins at the end of the follow-up period. Unexpectedly, in 7 of 25 subjects without mixed cryoglobulinemia before treatment, cryoglobulins became detectable after antiviral therapy.
(http://www.ncbi.nlm.nih.gov/pubmed/16416186)
So, question seems not well-studied yet…
Probably infected in 1977
2005 – diagnosed with HCV 1b, compensated F4, 15 mln viral load, ALT 320
2005-2006 – PegIFN/rib 48 weeks treatment, relapse
2016 – compensated F4, MELD 8-9, ALT 100-160
2018 – compensated F4, MELD 8, ALT 91 -
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