Wednesday, 18 January 2017

#ClinicSpeak: DMF and abnormal liver function

Do you know what your last liver function test showed? If not you should. #ClinicSpeak #MSBlog

Do you know what your latest liver function tests showed? If you have MS and are on a DMT you are likely to be having regular blood tests and one of them are LFTs or liver function tests. The paper below highlights that a rare complication  (<1 in 1,000) of dimethyl fumarate (DMF) may be abnormal LFTs. These tend to occur early and be mild and transient and not associated with severe liver injury. 

I personally don't recall seeing this in any of my patients. I thing to point out is that we shouldn't always blame the DMT when we see abnormal LFTs; in my experience they are usually due to another factor, for example excess alcohol intake, concomitant medications or food supplements. In addition, it appears that pwMS can develop autoimmune hepatitis that is a second autoimmune disease. I have seen three such patients, one on interferon-beta, one on glatiramer acetate and another on natalizumab. I have also seen several patients with MS develop viral hepatitis. What we tend to do if we detect abnormal LFTs is to withdraw the drug to see if the results normalise and then rechallenge. If the rechallenge results in the LFTs becoming abnormal then we can be more confident that it is the cause of the problem. 


The message from this post is that you need to engage with your own monitoring; don't be shy to ask about your blood results. 

Muñoz et al. Liver injury associated with dimethyl fumarate in multiple sclerosis patients. Mult Scler. 2017 Jan 1:1352458516688351

BACKGROUND: In pre-approval trials, there was an increased incidence of mild, transient elevations of liver aminotransferases in study subjects treated with dimethyl fumarate (DMF).



OBJECTIVE/METHODS: To evaluate post-marketing cases of drug-induced liver injury associated with DMF.

RESULTS: We identified 14 post-marketing cases of clinically significant liver injury. Findings included newly elevated serum liver aminotransferase and bilirubin levels that developed as early as a few days after the first dose of DMF. The pattern of liver injury was primarily hepatocellular. No cases resulted in liver failure.

CONCLUSION: Health professionals should be alerted to possible serious liver injury in patients receiving DMF.

CoI: multiple

7 comments:

  1. How is abnormal defined and how can the patients monitor their bloods? If something is abnormal, is there a particular biomarker that we should look into or shall we check for a combination of indices?

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    1. ask for a copy of your bloods... they will have the normal range on one side and your measurements next to it. usually the pathology will flag (in red or some other way) those that below the expected values. you can also sit with dr google nad google each label to see what it is, what it does, what it means etc lol

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  2. Sadly blood monitoring seems to vary a lot throughout the UK and Ireland. Many Tysabri patients have bloods monitored every 3 months if they are lucky. Some have a blood sample taken monthly from the pre infusion cannula-seems pointless. I live in Belfast and our guidelines are to have FBC, LFTs, U's + E's checked 2 weeks begore 4 weekly infusion. My WBC is usually high and the 2 week window gives a chance to see if i have an infection starting and repeat bloods/treat if necessary. Often this is an increase due to Tysabri itself but 4 times it has been due to shingles.
    It baffles me that guidelines can vary, even down to an hours post infusion monitoring.
    What happened to the TOUCH guidelines?
    Tina Mc Gonagle

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    1. Natalizumab (Tysabri) increases your white cell count. It shifts the so called marginating pool into the blood. Marginating lymphocytes are the pool of cells rolling around on the surface of blood vessels. By blocking VLA-4 (the one side of the velcro) the cells can't stick to the blood vessel wall.

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    2. Sorry only seeing your reply now.
      That makes a lot of sense.
      Thank you

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  3. dt in our centre, we give patients on DMT a blood monitoring booklet for them to be more involved in their treatment. Some are better than others and the uptake is on the minority. We discuss with patients what we monitor and the normal parameters. There needs to be a balance and effective communication with what abnormal results mean and how we the clinicians and the patients themselves manage that.

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