Transplant After SVR

[Rockerforlife]

Here is a very interesting question thats been on my mind this morning:
If a person gets SVR first,then decides to have a liver transplant after....would the virus return with a vengance? or would i have a brand new shiny liver for life?....i would think the "occult virus" would be totally eradicated

[HectorSF]

Although transplantation is effective for treating decompensated cirrhosis and limited hepatocellular carcinoma associated with hepatitis C, HCV reinfection is virtually the rule among transplant recipients. Reinfection of the graft is associated with more rapidly progressive disease, with a median time to cirrhosis of 8 to 10 yr.

"Antiviral treatment in patients with hepatitis C virus-related cirrhosis awaiting liver transplantation"
Pierluigi Toniutto,1 Carlo Fabris,1 Davide Bitetto,1 Ezio Fornasiere,1 Elisa Fumolo,1 Rachele Rapetti,2 and Mario Pirisi2

The strongest rationale to treat HCV-positive cirrhotics on the waiting list for LT is provided by the evidence that those who achieve SVR can benefit both in term of liver function, which improves, and HCV recurrence rate in the graft, which decreases. Furthermore, at least for a few patients, just being HCV RNA negative while on treatment at the time the transplant operation is performed may be sufficient to prevent post transplant HCV recurrence (Kuo et al 2006). It is important to note, however, that these results have been obtained in small and uncontrolled clinical studies, which enrolled overall less than 300 patients with a relative short period of follow-up. For these reasons, to date, to treat with antiviral therapy all HCV-positive patients who are listed for LT can not be recommended. Rather, these observations should stimulate a very important debate in the liver transplantation community, ie, if the actual organ allocation policy should be changed, conferring priority in the waiting list to HCV-positive patients treated with antiviral therapy who achieve virologic endpoints, either on or off treatment. Performing the LT when serum HCV RNA is undetectable could represent a promising way to prevent HCV recurrence, that is the most important predictor of reduced survival post LT. The rate of SVR is influenced, as in immunecompetent patients treated for chronic hepatitis C, by viral load at baseline, slope of HCV RNA decline during treatment and, most importantly, HCV genotype. In particular, the risk-benefit of antiviral treatment in cirrhotic patients infected by HCV genotype 1 is unclear, since SVR rates are extremely low. Since the tolerability of antiviral therapy in these very difficult to treat patients is limited, and, independently of neuthrophil counts, life threatening infections are not uncommon, it is often necessary to reduce the doses of both interferon and ribavirin. Moreover, only a limited proportion of patients with advanced and decompensated liver disease awaiting liver transplantation are eligible for therapy; they should not be treated outside clinical trials, to be conducted, under strict surveillance, preferably in experienced centers. The best way to manage antiviral therapy in HCV-positive patients awaiting LT is probably to start treatment as soon as patients are registered in the LT waiting list; this may allow the patients to be given a possible life-line, if their disease is to get worse sooner then expected. Furthermore, antiviral treatment should probably be stopped in the absence of early antiviral response. The subgroup of patients who could gain most from antiviral therapy before transplantation is that of patients with HCV-related Child-Pugh class A cirrhosis with HCC, preferentially related to HCV genotype 2 or 3 infection, scheduled to obtain an early liver transplant from a deceased donor or awaiting living donor LT.
Several questions remain unanswered and represent the goals of future studies. First of all, since SVR rates in HCV-positive patients awaiting LT treated with the combination of standard interferon plus ribavirin remain suboptimal, large clinical trials evaluating the efficacy of the combination of pegylated interferons with ribavirin are urgently needed. Secondly, it should be investigated whether the systematic use of GCSF and erythropoietin in preventing cytopenias during antiviral treatment allows higher SVR rates. A third, very important issue regards the possible benefit related to longer duration of antiviral treatment employing reduced doses of standard or pegylated interferon with or without ribavirin in terms of slowing fibrosis progression, in the absence of HCV clearance. Recent data coming from the HALT-C clinical trial (Everson et al 2006) clearly showed that patients with advanced liver diseases (ie, cirrhosis and platelets count ≤125000/mm3) previously non responders to antiviral therapy, when retreated with pegylated interferon α-2a in combination with ribavirin, achieved a SVR only in 9% of cases. Importantly, a benefit in reducing the progression of liver disease could be demonstrated only for patients who achieved a SVR. The HALT-C trial, therefore, does not support the strategy to retreat for longer periods of time HCV cirrhotic patients, non responders to previous treatments, as far as the aim of treatment is to stop the progression of liver disease. Finally, the poor tolerability and limited efficacy of current treatment strategies highlight the need for alternative drugs able to induce a more vigorous HCV viral decline without prohibitive side effects. Several promising new compounds administered orally have been discovered and are currently undergoing clinical development. In particular, two HCV NS3 serine protease inhibitors, named bocepravir (Schering-Plough, USA) and telaprevir (Vertex Pharmaceutical, USA), alone or in combination with pegylated interferon, determine a 2 to 4 log10 reduction in HCV viral load along a short period of time, although with rapid insurgence of escape mutants. In LT centres where the time of the transplant operation can be predicted with reasonable accuracy, potent antiviral regimens including these new drugs might prove to be most effective when used, for a limited period of time, by HCV patients on the waiting list.

Hectorsf

[eureka254]

In my mind, the main goal of treating to attain SVR, esp. for cirrhotics, IS to avoid progressing to transplant stage.  Most of the literature seems to support that if one achieves SVR through treatment (keeping in mind that many of those with Stage 4 livers, unfortunately, cannot tolerate treatment), the liver will maintain enough functionality to not need transplantation.  Also, as mikesimon said, there's a population that manages to attain SVR with a new liver if they are UND at time of transplant.

However, there are situations that might indicate the need for liver transplant even after SVR, for example, primary liver cancer (HCC), which remains a risk esp. for cirrhotics, even with preserved liver function after SVR.  To date, the only successful curative treatments for HCC is either resection or transplantation, so there are other factors beyond "svr or not" that can play into the need for transplantation.
~eureka

[Rockerforlife]

I dont think most people would go for a transplant anyway after attaining SVR,why go tru the hassle when the "SVR liver" should last the remaining years of the patient anyway ...but under certian conditions i could see some getting a transplant after SVR,one would be if the "SVR liver" was badly damaged ....so i guess transplant after SVR  does happen

[mikesimon]

The new liver would be HCV free if the patient was truly an SVR. I believe that there are  instances of recurrence but I suspect that those patients may not have actually SVR at the time of surgery. Some patients who are undetectable at EOT and are transplanted remain virus free post transplant and perhaps had those patients waited the requisite time they would have been SVR.
If a transplant candidate has a shot at SVR and can tolerate treatment I think treatment is something to strongly consider because treatment post transplant can be harder to tolerate and there may be less chance of achieving SVR with the current drugs, The virus is also often significantly more aggressive in the transplanted liver and that can be a serious problem. I treated within 2 months of my surgery for that very reason - the virus was extremely virulent.
I don't think occult virus would be an issue because I have seen nothing that suggests that is. SVRs who get a new liver remain virus free. Occult becoming full blown HCV sounds good because of the intense immunosuppression right after transplant but I have never seen an incident of it. To the contrary I have seen articles which discussed this issue in support of the premise that occult doesn't react like that when the host is immunosuppressed. Whether there are any traces of occult virus post transplant is something I know nothing about. I am somewhat curious about it though.
Mike
Mike