Aa
What new treatments are on the horizon?
Some background info: My husband tried the triple treatment with telapevir pre-transplant. As he had decompensated end stage liver disease he was only able to stay on it for 5 weeks. Despite this, he remained "unquantifiable" (<43) for 8 months. He had a liver transplant in early June. VL now shows 250,000. His doctor recommends biopsy at 6 months and no treatment of Hep C for a full year.
As he was on this triple treatment pre-transplant, I am assuming he will not be able to go back on it post transplant.
Can anyone direct me to any information on new treatments, trials, research studies that are currently going on for post transplant patients with recurring Hep C.
Thanks for your help.
Nan
As he was on this triple treatment pre-transplant, I am assuming he will not be able to go back on it post transplant.
Can anyone direct me to any information on new treatments, trials, research studies that are currently going on for post transplant patients with recurring Hep C.
Thanks for your help.
Nan
Hi Bill
Thank you for your post. Trust me, I wasn't trying to rush it. I just wanted to do what I have been doing since we found out he had Hep C and ESLD and that is to try to learn as much as I can about his disease and help him to survive. I know as long as he has this virus, the fight will go on so as the saying goes "knowledge is power".
Thank you again.
Nan
Thank you for your post. Trust me, I wasn't trying to rush it. I just wanted to do what I have been doing since we found out he had Hep C and ESLD and that is to try to learn as much as I can about his disease and help him to survive. I know as long as he has this virus, the fight will go on so as the saying goes "knowledge is power".
Thank you again.
Nan
They will normally wait at least year to treat post-transplant because they have to make sure any rejection chances are minimized and all the immunosuppresents are stabilized. Also as Hector's information stated they might wait until there's signs deterioration in the new liver before deciding to treat. They will do a biopsy 1 year post transplant. Take your time, you'll have some bumps to work through first year or two, everyone does, and see how it goes. It's enough to just get through the post transplant period without jumping into treatment. Not sure how much we can all take but it's enough! :)
Thank you so much for your warm congratulations. It is so great to hear from someone 5 years post transplant that's still having "wonderful" days.
I was watching NYMed, a new tv series showcasing medical dramas at NY area hospitals (real people/no actors). The second episode included a liver transplant patient. I cried like a baby watching their story. I think we all have this common bond and understand everything we have and are going through.
My husband's doctor said the same thing about the protease inhibitors and transplant patients. His second followup Hep C test shows the VL has doubled but still relatively low at about 500,000. I think we're on uncharted waters since he actually took the Incivik for 5 weeks and remained "unquantifiable" for 8 months before he was transplanted. Will there be any long term benefit to this? Only time will tell.
They did an ultrasound of his new liver yesterday because his liver enzymes levels came back high last week. (have no results yet) So we are still not able to really enjoy the moment fully. But I know it will come.
Hope all goes well with the kidney issues and you can have many more wonderful days ahead. Thank you so much for sharing your story!
Nan
I was watching NYMed, a new tv series showcasing medical dramas at NY area hospitals (real people/no actors). The second episode included a liver transplant patient. I cried like a baby watching their story. I think we all have this common bond and understand everything we have and are going through.
My husband's doctor said the same thing about the protease inhibitors and transplant patients. His second followup Hep C test shows the VL has doubled but still relatively low at about 500,000. I think we're on uncharted waters since he actually took the Incivik for 5 weeks and remained "unquantifiable" for 8 months before he was transplanted. Will there be any long term benefit to this? Only time will tell.
They did an ultrasound of his new liver yesterday because his liver enzymes levels came back high last week. (have no results yet) So we are still not able to really enjoy the moment fully. But I know it will come.
Hope all goes well with the kidney issues and you can have many more wonderful days ahead. Thank you so much for sharing your story!
Nan
Hi Nan,
My husband had his transplant 5 years ago this month - on 7/31/2007. He had HCV, type 1 - and of course it came back. I "feel" your descriptions of your husband's renewed peace now after his surgery, and the chance you have BOTH gained. The stress of this illness leading up to transplant is so hard. The misery the patients are in is palpable. I too was a caregiver (the only one for my hubby) and it was grueling. He too had rampant encephalopathy and has some memory issues (just a few - nothing major) post transplant, even now. We make a joke out of it now...They didn't treat him with Pegylated Interferon until June 2010 (he was too sick pre-transplant to be treated for HCV). He achieved a 2 log drop in 12 weeks on PegIntron. Unfortunately after stoppping treatment it came back, and he is NOW on Infergen/Ribavirin (for only 10 weeks right now). At our center in Atlanta, GA they won't use the protease inhibitors yet on transplant recipients - not enough data and they don't want to risk the patients, so we wait, and hope for them to be approved in transplant recipients. But, my husband is able to work (part time - he couldn't at all for several years before his transplant; he was so sick) and he plays his guitar again, drives me CRAZY, and is around to be a general pain in the neck...LOL...these are wonderful days. He has some kidney issues starting now, from the meds, and we are in a learning curve now again about that, but really, things are quite good, still. Anyway - I just wanted to say "congratulations" to you both. And I concur on lactulose. Terrible awful stuff. Take care and REVEL in this time - get some rest!!!
My husband had his transplant 5 years ago this month - on 7/31/2007. He had HCV, type 1 - and of course it came back. I "feel" your descriptions of your husband's renewed peace now after his surgery, and the chance you have BOTH gained. The stress of this illness leading up to transplant is so hard. The misery the patients are in is palpable. I too was a caregiver (the only one for my hubby) and it was grueling. He too had rampant encephalopathy and has some memory issues (just a few - nothing major) post transplant, even now. We make a joke out of it now...They didn't treat him with Pegylated Interferon until June 2010 (he was too sick pre-transplant to be treated for HCV). He achieved a 2 log drop in 12 weeks on PegIntron. Unfortunately after stoppping treatment it came back, and he is NOW on Infergen/Ribavirin (for only 10 weeks right now). At our center in Atlanta, GA they won't use the protease inhibitors yet on transplant recipients - not enough data and they don't want to risk the patients, so we wait, and hope for them to be approved in transplant recipients. But, my husband is able to work (part time - he couldn't at all for several years before his transplant; he was so sick) and he plays his guitar again, drives me CRAZY, and is around to be a general pain in the neck...LOL...these are wonderful days. He has some kidney issues starting now, from the meds, and we are in a learning curve now again about that, but really, things are quite good, still. Anyway - I just wanted to say "congratulations" to you both. And I concur on lactulose. Terrible awful stuff. Take care and REVEL in this time - get some rest!!!
"When he is able, get out, walk, look at the sky and enjoy each day."
Great advice and just what we plan to do...
Thank you all for all the support along the way.
Nan
Great advice and just what we plan to do...
Thank you all for all the support along the way.
Nan
Day by day, a good attitude to take.
Tx with decomepenasted cirrhosis was really hard on me. This last time, over 2 years since my tp, though not a walk in the park, it was SOOOOO much easier.
For now, just let him heal.It takes time to recoup.
When he is able, get out, walk, look at the sky and enjoy each day.
Tx with decomepenasted cirrhosis was really hard on me. This last time, over 2 years since my tp, though not a walk in the park, it was SOOOOO much easier.
For now, just let him heal.It takes time to recoup.
When he is able, get out, walk, look at the sky and enjoy each day.
"Unfortunately what has happened to your husband is quite common post transplant. It is pretty much universal that patients reinfect their donor liver post TP. The virus was still in his body somewhere, although it was undetectable according to the viral load test he had. The 5 weeks of treatment wasn't able to eliminate all of the hepatitis C virus in his system. Once he had the transplant the immunosuppressants and other other drugs create an environment where the virus rapidly replicates."
Though I didn't know for sure, I figured that's what happened so I wasn't too surprised when it did happen. I guess I was hoping that he would beat this thing by some miracle. Heck, who would have thought that he would be "unquantifiable" for 8 months after only 5 weeks of treatment?
I am just so grateful that he is finally having some peace after so much stress and illness. His recovery so far is wonderful. Six weeks after transplant he has no rejection symtoms and "other things" are actually beginning to normalize which means so much to him as a man...
So we are so thankful and we will just take things day by day enjoying life as best we can.
Though I didn't know for sure, I figured that's what happened so I wasn't too surprised when it did happen. I guess I was hoping that he would beat this thing by some miracle. Heck, who would have thought that he would be "unquantifiable" for 8 months after only 5 weeks of treatment?
I am just so grateful that he is finally having some peace after so much stress and illness. His recovery so far is wonderful. Six weeks after transplant he has no rejection symtoms and "other things" are actually beginning to normalize which means so much to him as a man...
So we are so thankful and we will just take things day by day enjoying life as best we can.
You certainly provided us with a lot to chew on. My husband had such a difficult time on triple treatment (finally had to stop because of severe anemia) that the thought of his going back on it is just too hard to think about right now. Fortunately, we will not have to address it until some time in the future.
We will definitely be keeping up with this along the way and asking the right questions from those who should know. The thing about experiencing everything we have over the last 19 months is it does make you wiser, more knowledgeable and more careful in decisions made.
Thank you so much, Hector. You are always such a wealth of information. I truly appreciate your efforts as I know everyone on this forum does.
We will definitely be keeping up with this along the way and asking the right questions from those who should know. The thing about experiencing everything we have over the last 19 months is it does make you wiser, more knowledgeable and more careful in decisions made.
Thank you so much, Hector. You are always such a wealth of information. I truly appreciate your efforts as I know everyone on this forum does.
Nan,
Here is an excellent current paper on managing recurrent hep C in liver transplant recipients as it is done at Methodist University Hospital. This is where Steve Jobs of Apple fame received his liver transplant.
“Management of Hepatitis C Virus Infection in Liver Transplant Recipients”
Gastroenterology & Hepatology Volume 8, Issue 1 January 2012
Satheesh P. Nair, MD
Professor of Medicine
Director of Transplant Hepatology
Methodist University Hospital
University of Tennessee Health Science Center
Memphis, Tennessee
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277201/pdf/GH-08-56.pdf
Excerpt…
“G&H Does use of antiviral therapy reduce the occurrence of HCV infection in transplant
recipients? Which regimens are most effective in this setting?
SPN "There is a lack of consensus as to when antiviral therapy should be initiated following transplantation. Interferon-based antiviral therapy is not tolerated in the immediate post-transplantation period and therefore is not recommended unless there is severe recurrence or fibrosing cholestatic HCV infection. Other patients are typically evaluated for antiviral therapy around 6 months post-transplantation if there are no contraindications. Treatment is definitely encouraged in patients with genotype 2 or 3 HCV infection and in patients who have a history of response to treatment prior to transplantation. Some transplant centers delay treatment until these patients develop stage 2 fibrosis, but data show that achieving SVR in the post-transplantation setting can reduce the likelihood of progression of fibrosis. Given that 30–40% of patients with genotype 1 HCV infection will respond to interferon, I see no reason why treatment should be delayed.
Lack of response to treatment prior to transplantation does not mean that patients will fail to respond post-transplantation. Interleukin (IL)-28B data in the post-transplantation setting are intriguing, with studies showing that receiving an allograft with a favorable IL-28B genotype (such as CC) increases response rates even if the recipient’s IL-28B genotype is unfavorable (ie, TT). Antiviral treatment is not considered in patients
who have a contraindication to interferon, patients with active post-transplantation complications, and patients with prior severe side effects to interferon.
Once we have more effective regimens, almost all HCV-infected liver transplant recipients are likely to be treated. We will also see more clinicians using protease inhibitors in the post-transplantation setting once we gain more experience in this population. One of the principal concerns with these drugs is their possible interaction with immunosuppressive drugs such as cyclosporine, tacrolimus, and sirolimus. Given that cyclosporine drug levels are increased only 4-fold when this drug is coadministered with telaprevir (Incivek, Vertex; compared to a 70-fold increase for tacrolimus), cyclosporine seems to be an attractive choice for HCV-infected transplant recipients who are planning to use a protease inhibitor.
Any changes to a patient’s immunosuppression regimen should be made carefully to avoid rejection, especially in a patient who is on stable immunosuppression. My personal bias is to continue the current immunosuppression at a lower dose and follow the drug levels. Fortunately, we can monitor levels of these drugs and adjust the patient’s regimen as needed. We have a few patients at my institution, all with advanced fibrosis, who are on these agents, and we have been able to manage their immunosuppression well. The protocol at my institution is to stop tacrolimus on Day 1 of protease inhibitor therapy and measure tacrolimus levels 3 and 7 days later, and then adjust the dose of tacrolimus according to the level. At least in the small number of patients we have seen, a tacrolimus dose of 0.5 mg once per week is sufficient to maintain a drug level of 3–5 ng/mL. Prospective studies are being planned that should shed more light on the safety and efficacy of protease inhibitor–based antiviral therapy in transplant recipients. In my experience with the first generation of protease inhibitors, anemia seems to be the biggest challenge in this population—not the interaction between antiviral therapy and immunosuppressive drugs."
Cheers!
Hector
Here is an excellent current paper on managing recurrent hep C in liver transplant recipients as it is done at Methodist University Hospital. This is where Steve Jobs of Apple fame received his liver transplant.
“Management of Hepatitis C Virus Infection in Liver Transplant Recipients”
Gastroenterology & Hepatology Volume 8, Issue 1 January 2012
Satheesh P. Nair, MD
Professor of Medicine
Director of Transplant Hepatology
Methodist University Hospital
University of Tennessee Health Science Center
Memphis, Tennessee
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277201/pdf/GH-08-56.pdf
Excerpt…
“G&H Does use of antiviral therapy reduce the occurrence of HCV infection in transplant
recipients? Which regimens are most effective in this setting?
SPN "There is a lack of consensus as to when antiviral therapy should be initiated following transplantation. Interferon-based antiviral therapy is not tolerated in the immediate post-transplantation period and therefore is not recommended unless there is severe recurrence or fibrosing cholestatic HCV infection. Other patients are typically evaluated for antiviral therapy around 6 months post-transplantation if there are no contraindications. Treatment is definitely encouraged in patients with genotype 2 or 3 HCV infection and in patients who have a history of response to treatment prior to transplantation. Some transplant centers delay treatment until these patients develop stage 2 fibrosis, but data show that achieving SVR in the post-transplantation setting can reduce the likelihood of progression of fibrosis. Given that 30–40% of patients with genotype 1 HCV infection will respond to interferon, I see no reason why treatment should be delayed.
Lack of response to treatment prior to transplantation does not mean that patients will fail to respond post-transplantation. Interleukin (IL)-28B data in the post-transplantation setting are intriguing, with studies showing that receiving an allograft with a favorable IL-28B genotype (such as CC) increases response rates even if the recipient’s IL-28B genotype is unfavorable (ie, TT). Antiviral treatment is not considered in patients
who have a contraindication to interferon, patients with active post-transplantation complications, and patients with prior severe side effects to interferon.
Once we have more effective regimens, almost all HCV-infected liver transplant recipients are likely to be treated. We will also see more clinicians using protease inhibitors in the post-transplantation setting once we gain more experience in this population. One of the principal concerns with these drugs is their possible interaction with immunosuppressive drugs such as cyclosporine, tacrolimus, and sirolimus. Given that cyclosporine drug levels are increased only 4-fold when this drug is coadministered with telaprevir (Incivek, Vertex; compared to a 70-fold increase for tacrolimus), cyclosporine seems to be an attractive choice for HCV-infected transplant recipients who are planning to use a protease inhibitor.
Any changes to a patient’s immunosuppression regimen should be made carefully to avoid rejection, especially in a patient who is on stable immunosuppression. My personal bias is to continue the current immunosuppression at a lower dose and follow the drug levels. Fortunately, we can monitor levels of these drugs and adjust the patient’s regimen as needed. We have a few patients at my institution, all with advanced fibrosis, who are on these agents, and we have been able to manage their immunosuppression well. The protocol at my institution is to stop tacrolimus on Day 1 of protease inhibitor therapy and measure tacrolimus levels 3 and 7 days later, and then adjust the dose of tacrolimus according to the level. At least in the small number of patients we have seen, a tacrolimus dose of 0.5 mg once per week is sufficient to maintain a drug level of 3–5 ng/mL. Prospective studies are being planned that should shed more light on the safety and efficacy of protease inhibitor–based antiviral therapy in transplant recipients. In my experience with the first generation of protease inhibitors, anemia seems to be the biggest challenge in this population—not the interaction between antiviral therapy and immunosuppressive drugs."
Cheers!
Hector
Yes, good riddance Lactulose!
Have a safe and good trip!!!
☻/ღ˚ •。* ♥ ˚ ˚✰˚ ˛★* 。 ღ˛° 。* °♥ ˚ • ★ *˚ .ღ 。
/▌*˛˚ღ •˚ ˚…just sprinkling a little Love to you both...
/ \ ˚. ★ *˛ ˚♥* ✰。˚ ˚ღ。* ˛˚ ♥ 。✰˚* ˚ ★ღ
Hector
Have a safe and good trip!!!
☻/ღ˚ •。* ♥ ˚ ˚✰˚ ˛★* 。 ღ˛° 。* °♥ ˚ • ★ *˚ .ღ 。
/▌*˛˚ღ •˚ ˚…just sprinkling a little Love to you both...
/ \ ˚. ★ *˛ ˚♥* ✰。˚ ˚ღ。* ˛˚ ♥ 。✰˚* ˚ ★ღ
Hector
Thank you so much for the link. It looks like a great website for information.
I have bookmarked it so I can keep up on the latest advances.
I realize my husband is in a totally different place post transplant. He was so strong and endured so much with his diseased liver that I know it will be a good while before this becomes an issue for him. Our focus will be to make sure he has no rejection issues and that he builds up his strength. The really bad hepatic encephalopathy he experienced before transplant is gone but now he has some residual memory problems (minor by comparison) which he is working on with a speech therapist. He improves every day. The best thing is no more LACTULOSE!!
Thank you again!
I have bookmarked it so I can keep up on the latest advances.
I realize my husband is in a totally different place post transplant. He was so strong and endured so much with his diseased liver that I know it will be a good while before this becomes an issue for him. Our focus will be to make sure he has no rejection issues and that he builds up his strength. The really bad hepatic encephalopathy he experienced before transplant is gone but now he has some residual memory problems (minor by comparison) which he is working on with a speech therapist. He improves every day. The best thing is no more LACTULOSE!!
Thank you again!
Conclusion
"Prevention and treatment of HCV re-infection after liver transplantation remains a major unsolved clinical challenge. HCV-positive patients have poorer long-term outcomes after liver transplantation in comparison with patients with other underlying liver diseases. While treatment with pegylated interferon alpha and ribavirin can cure up to one-third of HCV-positive liver-transplanted patients, there are many promising drugs in clinical and preclinical development targeting either the virion or essential host factors. Strategies to prevent HCV re-infection include neutralizing antibodies or drugs targeting cellular HCV entry factors. Unfortunately, it will take at least several years until most of these drugs will reach routine clinical practice. Immunosuppressive medications may alter the course of hepatitis C after transplantation but conclusive data on the use of distinct regimens for HCV-infected transplant recipients are lacking. Thus, almost 30 years after the approval of the first calcineurin inhibitor and 23 years after the discovery of HCV, the optimal immunosuppressive strategy in HCV-positive liver transplant recipients still remains to be defined. However, acute rejection episodes and the need for steroid boli should be avoided as steroid bolus treatment is associated with reduced graft and patient survival and increase HCV infectivity."
----------------------------------------------------------------------------------------------
You can trust that your husband's doctors are aware of all this information in the article. Remember, the majority of persons in the U.S. who have liver transplants are persons who have liver disease caused by hepatitis C. The treatment your husband is receiving currently takes into account the need to control the progression of his hepatitis while at the same time caring for his body as it adjust to it new liver.
I hope this answer's your questions. If not, let me know about any questions you may have.
Congratulations to both of you!
I wish your husband a quick and bump free recovery. Having made it this far your husband is a fighter and when the time comes I have no doubt that he will battle his hep C with all of his strength.
√v^√v^√♥
Hector
"Prevention and treatment of HCV re-infection after liver transplantation remains a major unsolved clinical challenge. HCV-positive patients have poorer long-term outcomes after liver transplantation in comparison with patients with other underlying liver diseases. While treatment with pegylated interferon alpha and ribavirin can cure up to one-third of HCV-positive liver-transplanted patients, there are many promising drugs in clinical and preclinical development targeting either the virion or essential host factors. Strategies to prevent HCV re-infection include neutralizing antibodies or drugs targeting cellular HCV entry factors. Unfortunately, it will take at least several years until most of these drugs will reach routine clinical practice. Immunosuppressive medications may alter the course of hepatitis C after transplantation but conclusive data on the use of distinct regimens for HCV-infected transplant recipients are lacking. Thus, almost 30 years after the approval of the first calcineurin inhibitor and 23 years after the discovery of HCV, the optimal immunosuppressive strategy in HCV-positive liver transplant recipients still remains to be defined. However, acute rejection episodes and the need for steroid boli should be avoided as steroid bolus treatment is associated with reduced graft and patient survival and increase HCV infectivity."
----------------------------------------------------------------------------------------------
You can trust that your husband's doctors are aware of all this information in the article. Remember, the majority of persons in the U.S. who have liver transplants are persons who have liver disease caused by hepatitis C. The treatment your husband is receiving currently takes into account the need to control the progression of his hepatitis while at the same time caring for his body as it adjust to it new liver.
I hope this answer's your questions. If not, let me know about any questions you may have.
Congratulations to both of you!
I wish your husband a quick and bump free recovery. Having made it this far your husband is a fighter and when the time comes I have no doubt that he will battle his hep C with all of his strength.
√v^√v^√♥
Hector
Congrats for hubby getting a new liver. Hopefully he will be able to try the triple therapy again. Don't think any type of studies have been done on treating post transplant. Since he has a new liver and triple therapy worked before, maybe triple therapy would work again. Perhaps the resistance will be weak with new liver?
Anyway good luck to your hubby and you.
Anyway good luck to your hubby and you.
As you may know, post transplant recipients are the last ones to do any hep C trials.
Normally simply being post transplant disqualifies you.
Immune suppression meds can complicate tx, and numerically there are less of us.
The triple meds that have been approved for the general population since May 2011, but have not been used for that long on post tp patients.
I'd guess sometime after the orals are approved, they'll start allowing them for transplant patients too.
Here's a link for general information about new meds currently in trial.
http://www.hcvadvocate.org/hepatitis/hepC/HCVDrugs.html
Normally simply being post transplant disqualifies you.
Immune suppression meds can complicate tx, and numerically there are less of us.
The triple meds that have been approved for the general population since May 2011, but have not been used for that long on post tp patients.
I'd guess sometime after the orals are approved, they'll start allowing them for transplant patients too.
Here's a link for general information about new meds currently in trial.
http://www.hcvadvocate.org/hepatitis/hepC/HCVDrugs.html
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Unfortunately what has happened to your husband is quite common post transplant. It is pretty much universal that patients reinfect their donor liver post TP. The virus was still in his body somewhere, although it was undetectable according to the viral load test he had. The 5 weeks of treatment wasn't able to eliminate all of the hepatitis C virus in his system. Once he had the transplant the immunosuppressants and other other drugs create an environment where the virus rapidly replicates.
At this point the doctors will wait for significant fibrosis to occur before treating his hepatitis C. There is no advantage to treating his hepatitis C now. It is too dangerous in fact. The best chance he will have of SVR is after he has time to recover from the transplant operation and his health stabilizes. While not forgetting about his hep C, its importance is way down the list of items to be concerned about. Right now his focus show be on recovery from the surgery and adjusting to the changes in the medicines he is taking. Living with a new liver should be the main focus at this time. Try to take it one step at a time. There is no rush to deal with his hep C now. Now is the time for the doctors to monitor its progression that is all.
The doctor will keep an eye on his hep C and when appropriate he will have a biopsy to assess the progression of his fibrosis. Depending on the protocol at his transplant center they will treat his hepatitis C reinfection when he is healthy enough to treat and has the best chances of SVR.
Currently, the standard treatment protocol is peg-interferon and ribavirin. Post transplant patients have about a 30% chance of SVR. Since the response is so poor some transplant centers are treating certain selected patients with triple HCV treatment. Since this is such a new treatment and there are so few numbers of patients there is no published data on the outcomes of using triple therapy on post transplant patient groups.
As with all post transplant issues your husband's post transplant coordinator, surgeon or hepatologist is the best an only real source of information as to what the transplant center will do to try to eliminate his hepatitis C. So either call his coordinator now or go to his next meeting with his surgeon or hepatologist and ask the question, "What is the future plan for treating my husband's hepatitis C?"
Here is the latest info on hepatitis C treatment in post transplant patients.
----------------------------------------------------------------------------------------
"Immunosuppression, Liver Injury and Post-transplant HCV Recurrence"
From Journal of Viral Hepatitis
S. Ciesek; H. Wedemeyer
Posted: 01/17/2012; J Viral Hepat. 2012
http://hepatitiscresearchandnewsupdates.blogspot.com/2012/01/immunosuppression-liver-injury-and-post.html
Treatment of HCV Re-infection After Transplantation
"As long as no potent drugs or neutralizing antibodies are available to prevent HCV recurrence after liver transplantation, re-infection can still be treated with a combination of pegylated interferon alpha and ribavirin. However, the efficacy of this treatment is limited mainly by the poor tolerability in liver transplant recipients, and thus SVR rates are lower than in immunocompetent nontransplanted individuals. Overall, SVR rates after liver transplantation for HCV genotype 1 infection are around 25–30%. Furthermore, prolonged therapy seems to be required even in patients infected with the easier to treat genotypes 2 and 3 and extending antiviral therapy for more than 48 weeks might prevent virological relapse in many patients. IL28B genotypes of both the donor and the recipient are associated with response to PEG-IFNa-based treatment after liver transplantation, and determination of the IL28b genotype may therefore be useful in clinical practice to decide which patient should receive antiviral therapy. Importantly, successful treatment reduces liver-related complications in recurrent HCV infection.
Even though interferon alpha can be beneficial for many patients, it has to be considered that antiviral therapy can promote rejection especially in the early phase after transplantation. Thus, liver transplant recipients receiving standard antiviral therapy need to be monitored for acute cellular rejection and chronic ductopenic rejection. In addition, de novo autoimmune hepatitis may develop and immunological phenomena may even occur after treatment has been stopped. As the clinical course of HCV infection is largely influenced by co-factors, it is of particular importance in liver transplant recipients to avoid co-morbidities including ischaemic-type bile duct lesions and liver steatosis.
The use of the novel NS3/4A protease inhibitors seems to be limited in patients after liver transplantation as it has been shown that telaprevir increases tacrolimus blood levels by approximately 70-fold – precluding its use outside of clinical trials. Co-administration with telaprevir also affected cyclosporine exposure and cyclosporine half-life, but to a lesser extent. No data on drug–drug interactions between calcineurin inhibitors (CNI) and boceprevir are currently available. Clinical trials are under way to determine the safety of efficacy of triple therapy of hepatitis C in liver transplant recipients. Whether combinations of PEG-IFNa with other NS3/4A protease inhibitors or with calcineurin inhibitor-free immunosuppressive regimens are feasible remains to be determined.
Currently, more than 100 novel HCV inhibitors are under preclinical and clinical investigation. These can broadly be divided in direct antiviral agents (DAA) and host factor targeting antivirals (HTA). While DAAs target the virus directly and include NS3/4A protease inhibitors (first & second generation), NS5B polymerase inhibitors and NS5A inhibitors, HTAs target essential cellular factors like cyclophilin A, microRNA122 and CD81 antibodies. Disadvantages of some but not all DAA classes are that they are not effective against all HCV genotypes and that viral resistance is anticipated to become a major problem. HTAs may show broad activity across HCV genotypes and pose a higher barrier to drug resistance in comparison with DAA. It is expected that some of the novel drugs will reach the market in 2015; however, none of the new anti-HCV drugs are currently being evaluated in HCV-infected liver transplant recipients. The ultimate goal will be to introduce safe interferon-free combination therapies without significant drug–drug interactions leading to cure from HCV infection within a limited time frame."
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