Can someone with SVR relapse?

If you don't re expose yourself, can you relapse? Does SVR mean there is NO way you can relapse?

[lynda607]

Officially a person is considered SVR after one year.  Usually if the PCR is UND at 3 & 6 months the virus is unlikely to return.  We do see occasionally those who are UND at the EOT post 4 wk PCR only to have the virus return by 3 months.  I've read where there have been a few incidences of relapse in patients who had cirrhosis after a 3 & 6 month UND but that is  very rare.  

[MsDragonSlayer]

Thank you, that clears that up! :-) oh to be healed, what a celebration!
I may even get to see grand babies one day!

[MsDragonSlayer]

I guess this means that I should not do anything / expose myself to any chemicals, cleaning supplies, solvents, paint, alcohol, energy drinks, just anything in general that will tax the liver for that first year. I am a little confused to the healing process. I have read that the liver begins to heal immediately starting therapy, I have read from members here that healing does not begin till after tx is over. What is your take on that Lynda?

[lynda607]

Until the person becomes UND there is virus which is attacking the liver so I don't think the healing process starts immediately after starting treatment. Once a person becomes UND, there is no virus to attack the liver but these are very strong drugs which are being processed through the liver so in my opinion the healing process really doesn't begin until the person achieves SVR and the drugs are no longer in the body.   There are some people who keep elevated enzymes throughout the treatment process because the drugs are effecting the liver and they still go on to achieve SVR.  

The degree to which fibrosis reverses is based on the degree of liver damage prior to treating but the liver does regenerate, usually within 1-3 years.  

[curiouslady1]

Thank you.  Very helpful question and very helpful response.  Deserves to be bumped.

[eureka254]

"the healing process really doesn't begin until the person achieves SVR"
-------------------------
I beg to disagree.  The healing process continually happens in the liver, even in someone with chronic hcv... in fact, the problem hcv presents is that the regeneration of the liver cannot keep up with the damage being wrought by viral activity or for some, anyway.

The liver is remarkable for the very fact that it sustains insult and injury and continues to renew itself.  What makes SVR so important is that ceases the ability of the virus to outstrip the liver's regenerative capabilities.  When the liver stops healing it is because it has reached cirrhosis... that's why for some cirrhotics, if done early enough, getting to SVR can stop damage in its tracks and prevent ESLD if further insult to the liver can be maintained, and *possibly* reverse cirrhosis.  My take, anyway. ~eureka

[curiouslady1]

Thank you Eureka for the further clarification and elaboration.

[eureka254]

Just as a point of interest, in cases of liver surgery and liver donation, a healthy adult liver can tolerate 2/3 removal, and still regrow itself to normal size within 3 to 6 months... an amazing organ, isn't it?

[lynda607]

Not only is there the stage of fibrosis but there is also a grade of inflammation in those with hepc.  By healing process I mean no more damage is occurring within the liver because the liver is no longer inflamed which allows for fibrosis reversal.  Until there is total absence off the HCV virus, fibrosis cannot reverse hence I do not see the liver as "healing" itself in the true sense of the word.

[eureka254]

I understand it's a logical presumption, but in the case of hep c and the liver, there is no linear pattern.  A high degree of inflammation may correlate to response to viral activity, but individual inflammation does not equate to equal damage in every individual.  Also, remember that when cirrhosis sets in, damage continues with very little inflammation.  There are also plenty of folks who maintain high viral loads (and presumably high viral activity) yet do not sustain damage as a result of chronic infection... perhaps cases of the liver "healing" itself even in the presence of HCV virus.  No simple absolutes with the dragon.

[redsurfer]

your comment was helpful to me .because my enzimes came down right away with tx but became elevated at around 10 weeks .. i have been und since week 2 .. thats why they did another pcr test for me @week 15 and still und but elevated .enz..
i was worried but this does explain it..makes perfect sense ...so thanks i feel better ....

my dr did not make me feel better about this by asking me if i had been drinking alcohol..."um... no doctor... i cant even drink coffee not gonna be having cocktails right now"

[lynda607]

I am not saying that individual inflammation equates to equal damage in every individual.  If that were the case, those infected for the same amount of time would have the same degree of liver damage.
Liver fibrosis refers to the accumulation of tough, fibrous scar tissue in the liver. Formation of scar tissue is a normal bodily response to injury, but in fibrosis this healing process goes wrong. When hepatocytes (functional liver cells) are injured due to HCV infection the immune system is activated to repair the damage.  The injury or death (necrosis) of hepatocytes stimulates inflammatory immune cells to release cytokines, growthfactors, and other chemicals. These chemical messengers direct support cells in the liver called hepatic stellate cells to activate and produce collagen, glycoproteins (such as fibronectin), proteoglycans, and other substances. These substances are deposited in the liver, causing the build-up of extracellular matrix (nonfunctional connective tissue.  But as the inflammation and liver injury continue, scar tissue builds up and connects with existing scar tissue, which can eventually disrupt the metabolic functions of the liver. If the disease progresses, it can lead to cirrhosis.  
Now, staying on track with the OP's question: does the liver begin to heal itself as soon as treatment is initiated or does this occur once treatment has ceased?  It is safe to assume healing means can fibrosis reverse while undergoing treatment or does it occur when there is no longer HCV RNA in the liver, otherwise why would anyone treat?  The objective of treatment is to stop the virus from damaging the liver whether the deterioration process is moving slowly or quickly.
My answer still remains there cannot be any significant improvement in liver histology until the virus is eradicated from the body,  

[curiouslady1]

I think both of you are correct and thank you for a really helpful thread!

[Dee1956]

Thanks so much for your this information  was interesting and exciting My liver enzymes were approx in the 80's before starting my trial, after the trial they were all over the place, my doc said it was because I relapsed and my body was trying to equalize. now my enzymes are in the 20's, what a miracle

[MsDragonSlayer]

Lynda, I sure do appreciate all of your knowledge, you are quite informed. It's so great to have you here! From what I have gathered from this thread, the liver takes from 1 to 3 yrs to completely heal, depending on how much scarring we are reversing. So during this time of repair, I will do my best to not do anything to sabotage the healing process. I want to start painting again, I work with solvents and such, so will I wait to paint! Hugs to you all!
Carolyn

[eureka254]

"It is safe to assume healing means can fibrosis reverse while undergoing treatment or does it occur when there is no longer HCV RNA in the liver, otherwise why would anyone treat?"
--------------
Those who choose to treat most likely do not reflect visible "healing" or *reversal* during chronic infection; however, we all know there IS a population that chooses NOT treat, and for good reason. My point is, conversely, if healing/reversal cannot happen with chronic hcv, why are there Stage 0s choosing NOT to treat walking around after long-time infection?

As you pointed out, it is not the virus itself but the metabolic cascade initiated by immune response that causes fibrosis; so, theoretically, interrupting the sequence that produces the extracellular matrix even in the presence of chronic infection would "reverse" fibrosis. It seems we agree to disagree, as I remain unconvinced that histology cannot be improved in the presence of viral activity.

Some reading if you are so inclined:

Title:  Interferon gamma-1b for the treatment of fibrosis in chronic hepatitis C infection.  
Author:  Muir, A. J. Sylvestre, P. B. Rockey, D. C.  
Citation:  Journal of Viral Hepatitis May2006, Vol. 13 Issue 5, p322-328  
Year:  2006  
Abstract:  "Given that the complications of hepatitis C are due to fibrosis, we hypothesized that the antifibrotic effects of interferon gamma on stellate cells would lead to beneficial effects in patients with hepatitis C. Thus, we evaluated the safety and efficacy of interferon gamma-1b in patients with hepatitis C. A cohort of 20 patients with chronic hepatitis C who failed or were intolerant to previous interferon-alpha-based regimens received 200 μg of interferon gamma-1b subcutaneously three times weekly for 24 weeks. Liver biopsy was performed prior to and at the end of treatment. Biopsies were evaluated by a single blinded pathologist using the Knodell system modified by Ishak, and fibrosis was also quantitated by morphometric analysis. The study population was 75% male and 70% Caucasian. Mean age was 47.9 +/- 7.5 years. Eighteen of 20 patients completed therapy. One patient discontinued therapy because of constitutional symptoms. One patient discontinued therapy because of elevated aminotransferases greater than twice baseline. No serious adverse events occurred. Morphometric analysis revealed that six patients (30%) had >1% absolute reduction in fibrosis score. Four of 20 (20%) patients had improvement in Ishak fibrosis scores after treatment. In conclusion, interferon gamma therapy is safe and well tolerated in patients with chronic hepatitis C. Although we did not detect an overall reduction in fibrosis, interferon gamma-1b treatment led to a reduction in fibrosis in selected patients. These data provide a basis for further study of interferon gamma-1b in patients with chronic fibrosing liver disease."

Title:  Blockade of renin-angiotensin system in antifibrotic therapy.  
Author:  Yoshiji, Hitoshi Kuriyama, Shigeki Fukui, Hiroshi  
Citation:  Journal of Gastroenterology & Hepatology May2007 Supplement, Vol. 22, pS93-S95  
Year:  2007  
Abstract:  "Recent studies have shown that the renin-angiotensin system (RAS) plays a pivotal role in liver fibrosis. An intrahepatic RAS is expressed in chronically damaged livers, and angiotensin-II (AT-II) reportedly stimulates contraction and proliferation of the activated hepatic stellate cells (Ac-HSC), and increases the transforming growth factor-β (TGF-β) expression through angiotensin type-I receptors (AT1-R). Some studies have demonstrated that the clinically used angiotensin-converting enzyme (ACE) inhibitor (ACE-I), and AT1-R blockers (ARB) significantly attenuated experimental liver fibrosis along with suppression of the Ac-HSC and hepatic TGF-β expression. Angiotensin-II also stimulates the tissue inhibitor of metalloproteinases-1 (TIMP-1) in a dose- and time-dependent manner via protein kinase-C as an intracellular signaling cascade in the Ac-HSC, and these effects are completely suppressed by ARB. Combination treatment with low-dose interferon (IFN) and ACE-I exer
ts a stronger inhibitory effect than either single agent on its own. In humans it has been reported that ARB markedly improved the liver fibrosis score and TGF-β expression in patients with chronic hepatitis C and non-alcoholic steatohepatitis. Serum fibrosis markers also significantly improved by treatment with low-dose IFN and ACE-I in patients with chronic hepatitis C, refractory to IFN monotherapy. Collectively, these data suggest that the interaction between AT-II and AT1-R plays a pivotal role in liver fibrosis development. Because both ACE-I and ARB are widely used in clinical practice without serious side-effects, these drugs in combination with IFN may provide a new strategy for antifibrosis therapy."

Though certainly the new therapies are closing the gap for previous non- and null-responders, I firmly believe there remains research to be done into anti-fibrotic treatments for those who remain unable to rid their hcv.  My hope is that science can not only continue to work on anti-virals, but perhaps with more research we can also understand and learn to break the cycle of fibrosis progression wrought by active hcv.

[eureka254]

You definitely asked some very thought-provoking questions, and I thank you.  I should add, I do believe that SVR is durable for 99.9% of the population... there are always exceptions to the rule, but I'll leave the stirring of that pot for another day :). ~eureka