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.

I 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”?

Hi, 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!

Hi, 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.

Hi, Gaj!

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.

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.

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”.

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.

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, 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.

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?