Pegasys and elevated ALT and Ferritin

[welshhuw]

Dear fellow MPN patients, I have been on treatment with Pegasys for the past 6 months at 65micrograms per week for my ET (CALRins5 - type 2) doing really well up until now with no significant side effects and platelets reducing from 1.3m to within normal range of 300k. However, since beginning treatment my ALT and Ferritin levels have gradually increased to ALT 283 and Ferritin 668. Saw my consultant yesterday who has cut my dose to 45microgram weekly. Just wondered if there are any other patients out there who have experienced a similar situation and can share their experience or advice. Thanks

[Susana7]

Hi, just read your post. I have been on Pegasys for PV for over 4 years. My liver counts (including ALT) have been up most of that time, but not enough to be of concern, in fact they oscillate up and down. The haemo says I have fatty liver (not alcohol related!) which seems to be a common occurrence in MPN patients. I currently only inject 45mcg every 3 weeks as a maintenance dose as my counts are all normal (I started at 90mcg/weekly and gradually reduced it). I don’t have high ferritin though, I think reducing the dose is a good thing anyway, given that your counts are normal. All the best to you, Susana x

[welshhuw in reply to Susana7]

Thank you Susana for your reply, elevated liver enzymes due to Pegasys doesn't seem to be a common problem but it's interesting that you have also experienced ALT variation. My Pegasys dose has been reduced from 65mcg to 45mcg weekly. If that doesn't do the trick the plan is to go for 45mcg every 2 weeks. Finger crossed . That being said, the ALT and Ferritin elevations may be totally unrelated to Pegasys. Warm regards, Huw.

[AndyT]

Hi Huw,

I’ve been on Peg for 4 years and have had a few episodes of raised liver counts but they have always resolved again.

Peg is a great drug but can affect other counts so it’s good to move to the lowest possible dose once your platelets are under control, which yours appear to be.

Once mine were stable in the 300’s we agreed to reduce my dose to 45mcg and stretch the intervals gradually - I’m now only injecting every 4 weeks, which keeps my platelets in range and avoids issues with liver, thyroid etc readings.

[welshhuw in reply to AndyT]

Thanks Andy for sharing your experience with PEGASYS. It’s good to know that you are doing well on a 45mcg dose monthly and still keeping your platelet count in the normal range. I will discuss this approach with my consultant, hopefully I can benefit from the same treatment strategy. Hope you continue to do well, warm regards, Huw.

[Alexbits]

Hi, Do you have any updates on this? How are your liver enzymes and ferritin on lower dosage?

[welshhuw in reply to Alexbits]

I'm pleased to say that reducing my Pegasys dose to 65 micrograms every 2 weeks has resulted in a reduction in my liver enzymes (GGT, ALP, Bilirubin all in normal range, ALT slightly elevated at 72). Ferritin also now in normal range at 335. My platelet count has increased slightly but is now just in normal range at 397. Moving forward, hopefully this reduced dosing regimen will be sufficient to control my platelets. I did come across some interesting research that appears to indicate a correlation between elevated ALT and Ferritin levels suggesting that Pegasys may cause iron overload in some patients. That being said, the patient population in the study was HCV, so the results need to be viewed with some caution.

Best regards, Huw

ncbi.nlm.nih.gov/pubmed/185...

[Alexbits in reply to welshhuw]

Hi, Huw, thank you very much for the details, this was helpful. I'm on 45mcg weekly, 8 weeks. In my last blood work, my ALT/AST were rised (112 and 94), other parameters were in normal range. This raise started synchronously with my injections.

From what I understand this could be some rare Pegasys side effect. Because even hepatologist I visited recently, strongly rejected connection between raised ALT/AST and Pegasys and said to do tests for HCV. I already read the article about iron overload, I plan to check my ferritin this week.

[Manouche in reply to Alexbits]

The ALT/ASAT is quite a common side effect of Pegasys (over 10%). I had roughly the same figures as yours after a couple on months at 45mcg. After 4 months of treatment the ALT is back to normal since last week and the AST is at 65. What helped was possibly a total alcohol abstinence for 2 months (?)

[Alexbits in reply to Manouche]

I see. That's helpful information. I don't drink at all for a year, maybe even longer So you did not take any drugs to help your liver and did not change the dose?

[Manouche in reply to Alexbits]

I started at 90mcg for a few weeks and then 45mcg for about 3 months. My haemo told me he expected the ALT/ASAP to progressively get back to normal values as the liver gets used to Pegasys.

[Alexbits in reply to Manouche]

I see, thanks

[Alexbits in reply to Manouche]

Hi Manouche, did you ever check your ferritin while on Pegasys?

[Manouche in reply to Alexbits]

No, not since I stopped being phlebotomyzed in October. I don’t know exactly why but I suppose he’s happy with the complete haematological response and the original ferritin level (?)

[Alexbits in reply to Manouche]

Ok. I see. Thanks.

[welshhuw]

You are very welcome, good to know you found it helpful. By the way, my ALT elevation also correlated with the start of Pegasys treatment, gradually rising over time. My haematologist also performed a full virology screen, HIV,HBV, HCV, all negative. As a precaution I also had a liver Fibroscan which produced a healthy reading of 6.1 kPa suggesting no significant fibrosis.

Good luck with your investigations, hopefully you can get to the source of the issue and things resolve for you soon. All the best, Huw.

[Alexbits in reply to welshhuw]

Thank you Huw!

[Alexbits in reply to welshhuw]

Hi Huw. Just got my latest ferritin and LFTs. Ferritin rose to 276 from 170 😕 So it looks I'm in same situation. My ALT is 60 which is only slightly higher than normal, AST and other enzymes are fine. But this is thanks to Heptral (ademetionine) tablets, took it for a week, liver protector, recommended by my hematologist. I'm not sure if it can fix the problem with iron 🙄

[welshhuw]

Sorry to hear about your results, there does appear to be a correlation between elevations in your ALT and Ferritin. On the positive side, your Ferritin, although elevated relative to baseline, it's still within the 'normal' reference range. Just before I started treatment with Pegasys both my ALT (32) and Ferritin (180) were well within the reference range. However after 6 weeks of treatment my ALT had risen to 76 and Ferritin to 427. Both parameters continued to rise during the following months on Pegasys and only reduced with Pegasys dose reduction. Interesting that you have been taking Heptral. I have also been considering a liver support supplement and have come across N-Acetylcisteine, which not only provides liver support but may also be beneficial in MPNs.

(researchgate.net/publicatio...

The other liver support supplement that I am considering is Milk Thistle. The downside is that in the typical formulations the bioavailability is very low. However, I have identified a phytosome based formulation (Swanson Ultra - Siliphos) with a significantly better bioavailability. Not sure yet, will discuss with my Haematologist.

Anyway, I hope things resolve for you and thanks for the info regarding Heptral. All the best, Huw.

[Alexbits in reply to welshhuw]

Hi Huw. Thank you. I'll check the N-Acetylcisteine, did not hear about it. I used Milk Thistle regularly, since I started Pegasys, in powder and in oil forms. I'm not sure if it made any difference, because my liver LFTs were climbing anyways until I tried Heptral. Take care.

[Alexbits]

So, I have an update on this. My ferritin rose to 414 after 6 months on Pegasys. ALT/AST were both raised. From what I understand, it's not iron overload, it's more likely an inflammation marker. Who knows.

I've been taking Heptral (ademetionine) tablets. It worked for me in reducing ALT/AST counts and keeping them around/below 100 and almost normal sometimes. I've tried stopping them, this caused elevation of ALT/AST.

50 days ago I changed my dose to 45mcg every 10 days instead of 7. After 4 injections, my ferritin is down to 358. ALT is a bit raised in my last results, but strangely it was OK in my previous results 2 weeks ago. GGT bit raised too.

I hope this information will come in handy for someone in the future.

[Mercedeshm]

Hi, the same thing has happened to me, my ferritin has gone up since I've been on Pegasys. How long did it take for it to go down since they reduced your dose? I was taking 65 and since 2 weeks ago I've been taking 45 a week, but my ferritin is still high. Thanks

[Alexbits in reply to Mercedeshm]

Hi. It goes down very slowly. It started to go down when I was on 45 every 10 days, from more than 400 to 280 after 3-4 months. Now it's still more than 300 because I inject a bit more than 45 every second time (same 10-day interval). The last time I checked it, it was 360. Hope this helps.

[fernie in reply to Mercedeshm]

I've just found I have high ferritin 366, and high GGT/ALT too. I'm on 45mg of pegasys every week. Been on it for 18months and bloods stable. No phlebs for one year. I'm concerned it's iron overload, as I have had that prior to my MPN. I'm a C282Y heterozygote. Anyone else? How are the ferritin levels going?

[Alexbits in reply to fernie]

Hi Fernie. My ferritin is down to 190. I'm on 45mcg fortnightly at the moment.

[fernie in reply to Alexbits]

Thanks for the reply Alexbits. I'm just thinking about extending my week to maybe 10 days and see how that goes. My Drs. don't seem to know what it's all about. Not due to see the haem. for another 3 months.

[Alexbits in reply to fernie]

Extending the injection interval will undoubtedly help. If your counts are stable for 18 months, you should be fine doing this. It's not medical advice. I am just sharing my experience after four years on Peg.

[fernie in reply to Alexbits]

Thanks again. I'm only just stable recently. My reds etc. came down quickly so i could stop phlebs quickly, but my platelets took a while. I have no spleen, so that probably doesn't help. I tend to do my own thing and then tell my Drs. I'm good at researching things so they know I'm not stabbing in the dark usually.