Relapse prediction from enzymes?

[Bill1954]

Increases in ALT Late in the Course of Interferon-based Therapy for Chronic Hepatitis C Predicts Relapse

http://www.hivandhepatitis.com/hep_c/news/2009/071709_a.html

This just appeared in my e-mail inbox. I find it very interesting; this scenario mirrors my initial treatment profile. I had an excellent biochemical response, followed by steady increases in liver enzymes; especially ALT. As I completed treatment at week 56, my ALT was 93 U/L. Has anyone else had this occur?

Bill

[Isobella]

Great information, Bill.  Thanks for posting.

Isobella

[Bill1954]

Hey, Izzy—

What a trip, huh? This is precisely what happened to me before I relapsed. Although they stress that liver enzymes don’t predict relapse per se, it’s an interesting correlation they found, isn’t it?
~~~~~~~~~~~

“ALT is an enzyme produced by hepatocytes (liver cells) under conditions of inflammation. Measured as an indicator of liver health, elevated ALT can signal liver injury due to a variety of causes including viral hepatitis and drug-related liver toxicity.

Monica Basso and colleagues from the University of Genoa in Italy studied 173 chronic hepatitis C patients who achieved virological clearance while undergoing interferon/ribavirin combination therapy.

Results

141 patients (58%) achieved SVR and 32 patients (13%) were initial responders who later relapsed.

Overall, 33% of study participants with undetectable HCV RNA had elevated ALT measured during at least 1 scheduled visit during a 24- or 48-week follow-up period (depending on HCV genotype).

The researchers found no association between ALT elevations during treatment and demographic features including age or sex, or with baseline clinical or viral parameters.

ALT elevations during the early weeks of treatment were not associated with sustained treatment response versus relapse.

From week 12 until the end of treatment, however, ALT elevations were 10 times more common among initial responders who relapsed than among sustained responders (90% vs 9%, respectively).

"The occurrence of elevated ALT levels in HCV-RNA-negative patients during pegylated interferon and ribavirin therapy is a fairly frequent and unpredictable phenomenon," the study authors concluded. "Although ALT elevation per se is not associated with a greater risk of relapse, its occurrence in the later phases of therapy is more common in relapsing patients."
~~~~~~~~~~~

Hope you’re doing well,

Bill

[YuK]

thanks Bill, I'll make a mental note of this info.

[FlGuy]

I read a subtlety that does not seem well explained in the article.  There are people who go through treatment with elevated (my definition of elevated for this purpose is:  higher than normal range as reported on a LFT test report) ALT.  That was my situation, elevated above range but fairly stable at those above-range levels.  

What is not clear to me in this article is whether the elevated ranges for this patients elevated even higher during those latter weeks or if the article means that during treatment the levels normalized only to be elevated later in treatment.

[frijole]

Bill .........First - you nearly gave me a heart attack.  I thought your title was personal and that your enzymes had increased.  Thank goodness that is not so.

I think I am in the minority percent here.  My pretreatment ALT was 28.  It rose for the first few weeks of tx and was back at 28 at week 12.  Throught the remainder of tx it was lower, with a low of 16 and an EOT of 20.

Now after treatment was the true incline which spoke of relapse!  Post 10 weeks -58, Post 12 weeks - 80, post 16 weeks -- 114.

Interestingly, my last ALT done 28 months after treating was 22 - and I still have Hep C.

Now what are your ALTs now, and how did they run on your failed treatment compared to your successful treatment.  I am like you.  I do feel it is an indicator.  Each person's personal ALT is different though.  My ALT which is always in the normal range should perhaps be in the teens.  I think this was the case with Zazza whose enymes were always in the normal range.

best to you, Bill
frijole bean

[frijole]

"What is not clear to me in this article is whether the elevated ranges for this patients elevated even higher during those latter weeks or if the article means that during treatment the levels normalized only to be elevated later in treatment"

I think it means that whatever your levels are they elevated higher than that later in treatment.

How are you?
frjiole

[Tippyclubb]

Oh boy Bill, not a good read for me as this is exactly what happen to me.  I am hoping it was the increased Riba that elevated the enzymes towards the end of tx.

[mikesimon]

"ALT elevations during the early weeks of treatment were not associated with sustained treatment response versus relapse.

From week 12 until the end of treatment, however, ALT elevations were 10 times more common among initial responders who relapsed than among sustained responders (90% vs 9%, respectively)."

I think their conclusion is basically that elevated enzymes at the end of treatment are more common in relapsers. Since they start at week 12 it may be that when UND the enzymes should begin to normalize. I have always like normal enzymes and have believed that if enzymes normalize it is a very good sign. High enzymes mean increased cell death and I always ask myself : "what is causing the increased cell death?". When the virus is active the immune response can be a cause as can the virus itself but when the virus is UND the response should lessen and the enzymes begin to normalize. I have never had elevated enzymes without a problem and I see way way too many lab results.
Really, I don't fine this article surprising at all - I hate high enzymes.
Mike

[frijole]

Right.  I hate high enzymes too.  Down with high enzymes.

frijole

[nygirl7]

High enzymes mean increased cell death and I always ask myself : "what is causing the increased cell death?".

I've always looked at it this way too. It doesn't mean that a higher ALT means relapse in everybody after week 12 because there are certainly other things that could cause cell death but just logically......if you are truly UND the virus should not be therefore causing more or new inflammation and the numbers should go down with the cell death lessening greatly.  

Cause and effect.  In 4 weeks I went from mid 200s to 20 - I was not UND but had almost a 3 log drop. So cause and effect less cell death less enzyme being released.
Logic.

[Bill1954]

Hey Kathy—

No, I’m fine! I guess I could have inferred that by the title of this post though :o). The pretreatment enzyme results for the second time around were AST 165, ALT 267. They quickly normalized by week 4 to AST 27, ALT 27. Both remained normal throughout the second treatment, and remain that way today (19/25).

Failed Tx I had high enzymes pre-treatment, normalized initially, then slowly increased through EOT when they were 58/93.

I don’t know what to make of your results; not much rhyme or reason, huh? I saw this last night and thought it portrayed my experience, and thought it was interesting. I sure hope you’re doing well, and enjoying the summer—

Bill

FlGuy—

I understand your question, but unfortunately the link to the original text in Hepatology (via Wiley) was broken, and I can’t access the Journal myself. If I get a chance at my next follow up with the liver doc, I’ll try to question them a little more. They’ve always been very helpful accessing and printing journal articles for me :o).

Be well—

Bill

[FlGuy]

I am well, Kathy. Thanks.  Livin' the dream here in Florida.  Hope you are okey-dokey too.

[frijole]

Your enzymes are to die for, my friend.  I think mine seem to display some sort of relationship that has been worked out between my immune system and the virons.  (live and let live, so to speak).  (whirled peas, that is)

bean

[newleaf09]

Don't jump the gun, Tippy.  Elevated enzymes for the 141 responders (in a single,small study) were NOT an indicator of failure for 9%.  They SVR'd in spite of rising enzymes.  It's good to be aware of possibilities but wait, wait, wait for the PCR's.

[Tippyclubb]

How long after tx  before you relapsed?


Before tx my enzymes were slightly elevated and a few weeks into tx they were well below normal.  At one point they rose into the 150's then went normal again.  At EOT they were in the 70's.  4th week pcr is coming up and I am worried, especially after reading this.  Throughout tx the fluctuating enzymes were a major concern.  

[Bill1954]

Tippy,

I think it’s very important to point out that there is no cause/effect noted here; it’s only a correlation they found, and as Newleaf points out, it’s not an absolute indicator. I did, however, find it interesting. Hopefully, it opens dialogue for further questions.

I (and most it seems) relapse within thirty days post treatment; I think this is very typical unless there is cirrhotic involvement. Hopefully, your situation will be attributed to some unknown issues, and not viral involvement.

Best to you with your upcoming tests, and let us know how things go, for sure.

Bill

[Bill1954]

Hey Mike;

I agree; the results as stated by Liz Hylemen are somewhat ambiguous. I think the full text would answer a lot of questions about this. Glad to see you poking around here, Mike—

Bill

[portann]

Note bene buried in details at:

http://www3.interscience.wiley.com/cgi-bin/fulltext/121582705/HTMLSTART

"Noteworthy, if viral clearance occurs the presence of elevated ALT is not a poor prognostic factor per se, and although its appearance during the late phase of therapy may suggest a higher risk of relapse, its occurrence should not be a reason for treatment discontinuation."

[portann]

Sorry, the text has a gazillion characters and is too long for even three posts. I can email the full text  if someone wants it and can't access it by this address:

http://www3.interscience.wiley.com/cgi-bin/fulltext/121582705/HTMLSTART

[frijole]

My PCR was 12 weeks after treatment and the VL was 680,000 IU/mL   My suspicion was aroused when I had a CBC and liver profile done for a breast biopsy 10 weeks after I had finished treating and the enzymes were high (for me) - higher than I ever had seen.  Then I knew there was something happening in my liver.
frijole

[nygirl7]

its occurrence should not be a reason for treatment discontinuation."


Oh h3ll no not till the fat lady sings and the proof is in your hand........twice.

[banarep]

what i did not see mention was what might have caused some of the ALT fluctuations.  During my first 12 weeks, I was diagnosed with pneumonia and had to go on antibiotics - this caused a rise in liver numbers, then if i use too much tylenol - this cuases a rise in liver numbers (i use hardly any now), so I think we have to be careful about worring about the numbers.

my last round of treatment, my numbers went to normal at week 20, stayed there till 6 weeks after treatment and I still relapsed.

[alagirl]

mine didn't go down until after tx and actually surged towards the middle, but I was an acute too - maybe that had something to do with it, don't know.