Does interferon use prior to liver transplant influence hepatitis C outcomes following transplantation?

[mikesimon]

"BACKGROUND.: The most frequent reason for orthotopic liver transplantation (OLT) in the United States is due to complications of hepatitis C (HCV). Recent reports have shown decreased survival for HCV after OLT. Of note, the use of interferon (IFN) products has become wide spread with the majority of HCV patients being treated before transplant. AIM.: To review the outcomes of HCV patients who have received IFN products before liver transplant compared with HCV patients those who have never received IFN. METHOD.: Single-center, retrospective review of patients transplanted for HCV since December 1998 (n=131). Primary endpoint is the effect of IFN exposure before transplant on posttransplant outcomes. RESULTS.: Patients receiving before transplant (pre-IFN group; n=45) had a more aggressive recurrence of HCV with earlier recurrence (181.1+/-236 days vs. 303.4+/- 327 days; P=0.031), frequency of recurrence [41/45 (91.1%) vs. 62/86 (72.1%); P=0.013], and 1-year recurrence free survival [20% (+/-0.06) vs. 48.2% (+/-0.05); P=0.005]. Survival difference was noted in the pre-IFN group at 1 year and 3 years [79.7% (+/-0.06) vs. 90.5% (+/-0.03); 65.7 (+/-0.08) vs. 75.9% (+/-0.05); P=0.05] when compared with patients not receiving IFN (n=86) before transplant. CONCLUSIONS.: Based on this study, interferon use before transplant for the HCV patient indicates poor outcomes After OLT. Because of the increasing numbers of HCV patients coming to transplant, validation of these results should be of utmost importance."

http://tinyurl.com/create.php

[Deb_c430]

Same here, but its interesting to read and hear the ideas,

[portann]

Out of my element here, but it does seem the one study you originally mentioned is very small, the participants are not evenly divided and the differences in percentages is also small, especially when applied to the actual numbers of participants. The conclusion seemed a a bit of a leap to me.

Also, the data reaches back to 1998, which does provide a longer optic but makes you wonder how different the SOC may have been. And it doesn't make clear where the SVRers are in all this.

Haven't read the Shiff study yet but I guess I wanted to weigh in somehow, partly as an excuse to wish you a Happy New Year and thank you.

Best regards,

Portann

[mikesimon]

I was and am somewhat skeptical about this article's conclusion. Bill, you are correct - I did not treat until after my transplant and as strange as it sounds I hadn't thought of that until you mentioned it. Thanks Bill for your consistent wide eyed approach. Many times you have seen a bigger picture than I and her you go again. My skepticism is based in part on your observation that, if true, we should have seen something about this possible relationship before now.
Kathy, I too thought reducing VL per-transplant was a beneficial approach and particularly if one became undetectable or better SVR. At least the SVR benefit isn't being questioned here.
Zazza, "Recent reports have shown decreased survival for HCV after OLT."
I don't think this refers (and I guess you don't either) to interferon use but rather to the observation that, overall, transplantation for HCV may not have as favorable an outcome as transplantation for other underlying disease. As to why TX pre-transplant could adversely affect outcome - I really haven't a clue. I am afraid that I'll sound stupider than usual if I say that perhaps the surviving virons from treatment are heartier which translates into a more rapid and aggressive recurrence in the new liver than would have otherwise been the case. I think that it has been shown that exposure to interferon/ribavirin does not result in resistance - at least, didn't with me - so I don't know what else to grab - this is a purely desperate move to offer some explanation to a theory I am not convinced of.

And there is this from Shiff et al.

Effect of pretransplant hepatitis C virus RNA status on posttransplant outcome.
Nudo CG, Cortes RA, Weppler D, Schiff ER, Tzakis AG, Regev A.

Center for Liver Diseases, Division of Hepatology, University of Miami, Leonard M. Miller School of Medicine, Miami, Florida 33136, USA. carmine.***@****

"Undetectable hepatitis C virus (HCV) RNA [RNA(-)] before liver transplantation (OLT) has been shown to decrease the rates of disease recurrence. We sought to determine whether RNA(-) subjects differ in post-OLT recurrence (virological/VR, histological/HR), graft failure (GF), or patient survival from RNA(+) patients using a retrospective review. From 1995 to 2004, a total of 49 patients were RNA(-) at OLT as a result of interferon-based therapy: 22 SVR and 27 with end-of-treatment response (ETR) transplanted when RNA(-) within 6 months of ET. Forty-eight RNA(+) patients were analyzed as controls. Virological recurrence (VR) was seen in 55% of RNA(-) subjects with no difference in HR between RNA(-) vs (+) groups, namely 36.7% versus 56.3% (P = .068), respectively. The RNA(+) subjects showed a lower time to HR (5.6 vs 11 months; P = .027). The SVR subjects displayed lower VR (36.4%) and histological recurrence (HR) (13.6%) compared to ETR (VR 70.4%, P = .023; HR 55.6%, P = .003) or RNA(+) (HR 56%, P = .0008). The SVR subjects, who were identified with a sensitive assay (SVR(S), lower limit <600 IU/mL) showed no VR, HR, or GF. The 1- and 5-year survivals were 87.8%/75.6% and 89.6%/77.8% for RNA(-) and (+) groups, respectively (P = .77). In conclusion, RNA(-)-transplanted patients displayed lower VR and longer time to HR. The SVR patients showed lower VR and HR compared to ETR and RNA(+) patients."

Bottom line is I have more questions than answers to this whole idea.

I would like willing to weigh in on this. He would definitely have better ideas than I. Maybe I can coax him to pop in.

Mike

[frijole]

Hi Bill - never catch you online.  That California time difference gets to me - besides I am in bed by 9.  Did you have a  good Christmas?  We did - cut out of town and walked on the beach (Gulf of Mexico).  Got a look at the border fence too -- nasty!

Bean

[Deb_c430]

Totally interesting,   saving this one!

[Bill1954]

Hi Kathy!

[Bill1954]

Wow, Mike; regardless of whether they are discussing graft or patient survival rates, the results are significant. I wonder why this hasn’t surfaced before? This is very new info; one would think that simple regression analysis should have found this by now.

I believe you were treatment naïve prior to transplant; come to think of it, I know several people here in town that never treated prior to TP as well; they have all done well, as you have. Very interesting info; I wonder how much this will influence care form here out, if any? At minimum, I imagine it well spur further study. Thanks for the information--

Bill

[frijole]

That is a real interesting study based on the abstract.  Since it is so important, I hope that they will continue to study this.  This means it is better not to treat for HCV until after you have a liver transplant?  In order to make the decision to not treat , the transplant must be imminent.  That is, you will need the transplant whether you treat or not.  

I had always thought it was better to try to rid yourself of the virus so as to not infect the new liver.  However, cirrhosis has such a negative impact on treatment that the SVR percentage rate is low.  It seems that this will change a lot of doctors' thinking.

Happy Hanukkah to you Mike, and a very Happy New Year too.
Kathy

[zazza]

"Recent reports have shown decreased survival for HCV after OLT."

Any idea why interferon tx pre transplant would contribute to this? If you have cirrhosis and are close to a transplant might it then be better to wait to treat until post tx if you have the choice?

[mikesimon]

"But who are the patients who still need a transplant after interferon treatment?"
   I have to assume it's "the people with SVR who still need a transplant" because their livers are basically shot.

The survival numbers confused me as well. I assume they are talking about patient survival and not graft survival but it is rather unclear.
                               1yr survival            3yr survival
Interferon                     79%                        65.7%
No Interferon                90%                        75.9%    

[zazza]

Interesting. But who are the patients who still need a transplant after interferon treatment? Is it the ones not cured? Or are there people with SVR who still need a liver transplant? If it is people with unsuccessful treatment could this have an impact, ie that their hep C virus is strong?

I didn't understand what all the numbers in the sentence about "survival difference" where referring to. Mikesimon, help!

[mikesimon]

link should be:   http://tinyurl.com/7geaxh