The good, the bad, and the ugly.

[Bill1028]

I'll get the bad and the ugly out of the way.  It's baaaack after 76 weeks of tx.  On my 1 month post tx heptamax, my VL is a low 987 and my ALT and AST are normal.  I'm not sure of what to make of this.  When I relapsed after the first round of tx, my VL, AST, and ALT doubled.  I have another VL scheduled in 3 weeks.  I'm hoping to pull off a NYGirl.  :)

Please don't let this discourage anyone, because I have about all of the negative predictors for SVR.  I have no regrets and I'm glad that I had the opportunity to treat.  I had a very easy treatment except for anemia and no post sx.  I feel absolutely great, except for when I received my heptimax fax.  That sucked!


The good:

My labs are bouncing back nicely.  My platelets due to cirrhosis are up to 110,000, they were 99,000 pre-tx.  I was borderline diabetic before treatment.  During treatment, I had to take oral meds to control my glucose.   Within 1 month, I'm no longer on meds and my glucose is normal.  On my labs, during treatment, I had 15 things out of range and 1 month post, I have 8, and every one has moved in the right direction.  Even my bilirubin moved into the normal range.

               ON TREATMENT           1 MONTH POST
Platelets          63,000                        110,000
Nuetrophils         864                             2,250
Hemoglobin       10.8                              12.6
WBC                 1.8                                4.1

NYGirl, what were your numbers when you thought that you relapsed?

Would I treat again?  Hell yeah, they say 3 times the charm.  I wanted to restart now and my wife said she would divorce me.  Now that's food for thought!

[mikesimon]

I have great respect for my team but - I don't think they increased my immunosuppression dose to deal with the HCV. I think it was the shotgun approach really. They put me on low dose interferon and tiny dose ribavirin in case it was the HCV and increased the anti-rejection in case it was rejection or to slow down my immune system so it wouldn't attack the HCV. My situation coincided with a major immunosuppression dose reduction - I was on 1 mg Prograf or maybe 2 mg EVERY OTHER day. I was told that this stimulated my immune system which started attacking the tiny bit of HCV in my liver and bystander cell damage resulted in enzyme elevation. I am not so sure that's what happened - really. Acute rejection and HCV reinfection are indistinguishable on biopsy. I still wonder about what happened.
Mike

[BThompson4]

Thanks for the articles about rejection.  Shows that tx can be really tough post-transplant.  

I've never had rejection problems, and even had a "no sign of rejection" comment in biopsy report done six months after starting tx.  I was on only 100 mg Neoral a day (50 mg bid; increased it a little during tx) for two years prior to starting tx, and alt/ast are both about thirty points under pre-tx levels.  Of course, your doctors at UMPC (spent a couple of days at the Wyndham on Forbes there two weeks ago; what an impressive hospital and fun town!) have increased your immunosuppression to deal with the hep c, so I don't know if low doses of Neoral are helping or hurting my viral load!

Facial fungus and uti are much after three days on Levaquin, so I am getting psyched up to do the last 12 weeks of tx if my pcr results are good on Monday.

[BThompson4]

Gut. 2007 Feb;56(2):237-42. Epub 2006 Jun 23.
High incidence of allograft dysfunction in liver transplanted patients treated with pegylated-interferon alpha-2b and ribavirin for hepatitis C recurrence: possible de novo autoimmune hepatitis?

Here is the abstract.  Tiny Url changed their format and I don't have the energy to figure it out.

BACKGROUND: Interferon may trigger autoimmune disorders, including autoimmune hepatitis, in immunocompetent patients. To date, no such disorders have been described in liver transplanted patients. METHODS: 9 of 44 liver transplanted patients who had been receiving pegylated-interferon alpha-2b and ribavirin for at least 6 months for hepatitis C virus (HCV) recurrence, developed graft dysfunction despite on-treatment HCV-RNA clearance in all but one case. Laboratory, microbiological, imaging and histological evaluations were performed to identify the origin of graft dysfunction. The International Autoimmune Hepatitis scoring system was also applied. RESULTS: In all cases infections, anastomoses complications and rejection were excluded, whereas the autoimmune hepatitis score suggested a "probable autoimmune hepatitis" (score from 10 to 14). Three patients developed other definite autoimmune disorders (overlap anti-mitochondrial antibodies (AMA)-positive cholangitis, autoimmune thyroiditis and systemic lupus erythematosus, respectively). In all cases, pre-existing autoimmune hepatitis was excluded. Anti-lymphocyte antibodies in immunosuppressive induction treatment correlated with the development of the disorder, whereas the use of granulocyte colony-stimulating factor to treat interferon-induced neutropenia showed a protective role. Withdrawal of antiviral treatment and treatment with prednisone resulted in different outcomes (five remissions and four graft failures with two deaths). CONCLUSIONS: De novo autoimmune hepatitis should be considered in differential diagnosis along with rejection in liver transplanted patients developing graft dysfunction while on treatment with interferon.

http://gut.bmj.com/cgi/content/abstract/56/2/237

[zazza]

Nygirl's number post tx was 65 IU/ml. Next time she was UND. The sensitivity of her test was 50 IU/ml. I hope you have it beat, you have done so many weeks: 48 + 76. Zazza

[mikesimon]

Am J Transplant. 2007 Jan;7(1):177-84.Click here to read Links
    Rejection under alpha interferon therapy in liver transplant recipients.
    Walter T, Dumortier J, Guillaud O, Hervieu V, Paliard P, Scoazec JY, Boillot O.

    Unité de Transplantation Hépatique-Fédération des Spécialités Digestives, Lyon, France.

    Interferon alpha (IFN) is the corner stone drug for the treatment of recurrent hepatitis C (HCV) in liver transplant (LT) recipients. One of its serious potential adverse effects is acute and chronic rejection. The aim of this study was to review our experience using IFN-based therapy, in order to examine the incidence and the risk factors for rejection, and the outcome of patients who developed rejection. Between September 1990 and December 2004, 70 LT recipients were treated. Patients started antiviral treatment 16 (1-137) months after LT. Histological follow-up was available in all patients according to protocol biopsies. Rejection was diagnosed and graded according to Banff classification. Twenty-one percent of patients developed acute rejection (5 mild, 9 moderate and 1 severe) during IFN-based therapy. Patients were treated for 8 (1-15) months prior to rejection. Previous history of acute rejection before IFN therapy and treatment with pegylated-IFN was significantly associated with rejection (p = 0.04 and p = 0.02, respectively). The rejection was successfully treated in 87% of patients. No chronic rejection or graft losses were observed. Acute rejection under IFN-based therapy often occurs in LT recipients, but early diagnosis with protocol biopsies and early treatment can lead to a favorable outcome.

    PMID: 17227566 [PubMed - indexed for MEDLINE]

[mikesimon]

Chronic Ductopenic Rejection in Patients With Recurrent Hepatitis C Virus Treated With Pegylated Interferon Alfa-2a and Ribavirin.
Stanca CM, Fiel MI, Kontorinis N, Agarwal K, Emre S, Schiano TD.

1 Department of Medicine, Mount Sinai School of Medicine, New York, NY. 2 Department of Pathology, Mount Sinai School of Medicine, New York, NY. 3 Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Australia. 4 Institute of Liver Studies, Kings College Hospital, London, United Kingdom. 5 Recanati-Miller Transplantation Institute, Mount Sinai School of Medicine, New York, NY. 6 Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY.

BACKGROUND.: Interferon use for post liver transplantation (LT) recurrent hepatitis C (HCV) has not consistently been associated with acute cellular rejection (ACR). We examined the incidence of chronic ductopenic rejection (CR) in patients receiving pegylated interferon alfa-2a and ribavirin (PEG) to treat recurrent HCV. METHODS.: A chart review of 12 patients developing CR while receiving an escalating dose regimen of PEG with protocol liver biopsies every 6 months was conducted. Values are shown as median (range). RESULTS.: Twelve of the 70 patients treated with PEG developed CR. Median age at LT was 53 (37-63) years; immunosuppression consisted of tacrolimus or cyclosporine with prednisone. PEG was started at 3.6 (0.2-13.5) years after LT. Two patients had one episode of ACR before PEG. Four patients had first ACR while receiving PEG. CR was diagnosed after 12 (4-17) months of PEG; by then 8 patients had undetectable HCV-RNA. Tacrolimus and cyclosporine levels (ng/mL) were 7.9 (3.2-18.9) and 76 (71-93) before PEG, and 6.9 (3.7-9.7) and 130 (81-153) at CR. Six patients were treated more than 1 year with PEG; three had undetectable HCV-RNA when CR was diagnosed. Five patients are being treated for CR; one has been listed for LT; two patients were retransplanted. Five patients died as a result of sepsis partially related to CR. CONCLUSIONS.: Treatment with pegylated-interferon alpha-2a and ribavirin may trigger rapidly progressive CR in patients with therapeutic immunosuppressive trough levels, with or without first inducing ACR.

PMID: 17667809 [PubMed - as supplied by publisher]

[mikesimon]

Thanks for the medhelp site. I have read about this but I didn't recall a member saying this happened to her - which is what I thought you were saying. I dimly recall Bill's post though.
The link to the article on graft dysfunction is unavailable for some reason. Are you sure the link is right?
Mike

[BThompson4]

Didn't find the study mentioned by Mrs. Ockert but this one is disturbing for post-tx treaters:

http://www.tiny.cc/VBGua

Gut. 2007 Feb;56(2):237-42. Epub 2006 Jun 23.
High incidence of allograft dysfunction in liver transplanted patients treated with pegylated-interferon alpha-2b and ribavirin for hepatitis C recurrence: possible de novo autoimmune hepatitis?

[BThompson4]

This thread has something on it.  A post by Bill 1954.  Looks like she was only UND at six months and relapsed at one year mark after the prednisone bolus.

http://www.medhelp.org/posts/show/270244

[mikesimon]

I do not recall the lady who relapsed following bolus steroid. Do you recall anything about that - name of lady, approximate date of thread or thread title? Mike

[BThompson4]

I think it was return to sender that had the post-tx positive then got to svr.

http://www.medhelp.org/posts/show/95830

[BThompson4]

I think a relatively low immediate post-tx viral load may not signal treatment failure.  There was discussion here fairly recently I think about how little troughs in the immune and tx processes may allow the virus to show up in low numbers and then be repressed back down to nothing.  NYGirl might be a prime example with her very low post-tx pcr at one month and then UND later.

I had no less than 16 bi-weekly UND pcr's since clearing at week 22 until a few weeks ago when I showed up with a 43 IU/ml on my most recent test.  I suspect it was brought on by an "immune crisis" when I spend two hours a day for three days almost literally swimming in poison ivy from an apple tree that had the vines and leaves wrapped around it.  Naturally it was my first exposure and knowledge of the plant and at age 52, so I had no idea what was happening until it was too late, and it really wrecked my immune system.

I am immune suppressed from liver transplant so symptoms (body did not attack the poison ivy aggressively) did not show up for almost a week after the exposure; in a normal person, I would have got the message withing 24 hours and probably limited exposure by quite a bit.  I slept only an hour or so for about a week and was a total wreck.  Developed a facial fungus, got attack of viral or fungal dermatitis on my scalp (a more-or-less constant condition while I had cirrhosis), and got my first urinary tract infection since pre-transplant days, and there is no sign of the uti going away after three weeks and three courses of antibiotics.

I am in week 60 of treatment and will keep at it if my most recent pcr is UND.  My situation reminds me of the mention of a lady on this board who was svr and relapsed after getting a prednisone bolus.  I took some extra cyclosporine (doubled my mg to 400 a day) for five days in order to sleep after a week of suffering, and I am sure that did not help my immune status, but it did repress skin outbreaks (just as often-prescribed for poison ivy prednisone would have, but without having to drive my blood sugars above 500, which happens in me with only about 40 mg of prednisone) and not become a raving lunatic from lack of sleep.  Hopefully the viral load did not/will not get out of the two or three digit range and was/could be suppressed.  I am running out of time to get to 72 weeks (I'm definitely stopping tx then.  If I get a very high viral load in my next pcr,  I will probably stop tx right away.

[Myown]

Sorry to hear this but I think your immune system will knock them down and especially because how different the labs looked when you relapsed before. Someone else had this happen besides NYgirl. Can't remember his name at this moment, but the doc said he relapsed and wound up his body cleared it or it was an error when they thought he relapsed - can't remember the whole story but he did wind up being SVR. Maybe someone else will remember - he was a big guy I remember that. I think(?) he did the test 2 more times after the one that said he relapsed, and all worked out for him.

Wish you the very best and I believe you will sharing good news with us when you get your next PCR.

[wyntre9]

I HOPE the Dr. is right and the spike in VL is an immune system response and not a relapse.

Hang in there and keep us posted,

wyntre

[mikesimon]

You may already be aware of the problems with HbA1c while taking ribavirin and for several months after stopping. The hemolytic anemia destroys the RBCs so they are looking at cells that may be 30 to 45 days old and assuming they are 120 days old. The result is that the number can be way too low. Mine was once 2.8 during treatment and I knew that couldn't be right - it wasn't. Mike

[mikesimon]

I was/am type 1b. I achieved SVR my last treatment which ended June 2004.
ALT is the most specific liver marker and my personal opinion (and that's not worth much) is that in a non cirrhotic liver low levels of ALT and AST, and I mean teens and low twenties, generally suggest that the liver is not undergoing significant injury. I know this isn't always the case but I think it is the case a lot more than not. Mike

[jmjm530]

I agree.

[FlGuy]

I read 'subsequent measures'  as subsequent measurement of viral load i.e. future PCR.

[jmjm530]

Just to clarify, I mean to add the test to the blood draw you already had taken -- not to any future blood draws.

[jmjm530]

Bill,

Just another thought.

If the lab still has enough viable blood which they often save for a period of time -- have your doctor add another test to the order. Specifically, Quest's "HCV RNA QUALITATIVE TMA". or sometimes written as " HCV RNA QUAL TMA". This particular test will probably be run in a different lab -- Nichols Institute in Curpertino California -- and is strictly a qualitative TMA with a sensitivity of 5 IU/ml. This is the test I have used post treatment and anecdotally have heard it may have fewer false positives. I wouldn't do this test instead of another Heptimax in 4 weeks, but in addition to.

I also would be curious what your doctor means by "subsequent measures", but I have a feeling he may not have meant "measures* but something more akin to post treatment dynamics. In any event, I still think little to lose by taking one or two doses (or half doses) of Peg, but easy for me to say because it ain't my belly it's going into to :)

All the best,

-- Jim

[Bill1028]

There is a ray of hope.  This is my email to my doctor and his response:

I just got my 1 month post-tx heptimax results and the VL is 987.  Is there any other explanation other than the dreaded relapse.  The reason that I'm asking is that the last time that I relapsed, my VL tripled and my ALT and AST doubled.  This time my AST and ALT went down. There is a person that did 72 weeks on a HCV website that had something similar to this.  She was re-tested a few months later was UND.  Is it possible that she had a false positive or her own immunity kicked in and eliminated the virus?

How would you interpret my Viral Load?  Would it be worth while to hit the virus with a half dose of Peg before it gets another foothold?


Doctor's response:

I have seen several cases where a low viral load after stopping treatment goes away with subsequent measures. Probably the immune system kicking in. I think there is still room for hope here. I can't see how a bit more interferon will make a difference, quite honestly.

subsequent measures?

[Bill1028]

Thanks everyone!

Jim, I did send my doc an email about adding some peg.

FLGuy,  My glucose shot up to 500 soon after starting tx.  To get it under control, I was taking 1000mg of glucafage in the morning and night and then they added 4mg of avandia.  I'm pretty in tune with my body and can tell when glucose was low or high.  I monitored it myself and the A1C confirmed it.  I did 72 weeks at full dose and tapered off tx from 72 to 76.  I can tell when the glucose was below 85, and that started about week 76.  My doc had me drop 1000mg glucafage and avandia.  By 3 weeks post, I was off everything. A1C is the average over 3 months.  Crazy huh?

Lilla, every doctor has their own ways.  If you want to know, tell your doc that you would like to know sooner.  A lot of docs now believe that 3 months post is as good as 6 months.  ALT and AST are not great indicators as you can see in my case, but they were the 1st. time that I relapsed.

[Forseegood]

so sorry to hear of this, but you do sound like a person who likes to focus on the positive, and I'm sure that'll get you through till you find some better answers for yourself...it does seem like you benefited from the drugs, so glad about that! be well!

[tulips27]

Ive had HCV for a very long time. For aout 20 years my SGOT and SGPT startted off in the thousands then after years hundreds then double the normal. The past 3 years they have been normal
so go figure. My VL is 8 mil and Im 2/2.
I wonder why now they are normal too.
Regards

Just doesnt make sense.