Tag Archives: hepatotoxicity

A bit too close to the edge

I get my feet wet

I was discharged Sunday. Six pounds lighter and pretty darn worn out after my adventure, but happy to be home. I am back on the antibiotic levaquin, my persistent cough is finally abating and David has made the feeding and fattening of Linnea his pet project.

On Tuesday I returned to Boston for labs, a CT scan and to meet with Dr. Shaw. My ALT/AST are continuing to come down, but are still elevated. The LDK 378 will be held for another week and I will have labs on Friday and again on Monday to make sure the downward trend continues. Although I don’t have the radiologist’s report yet, Dr. Shaw reviewed the scans and feels that the activity in my lungs is at the very least stable, and at the very best, maybe even slightly improved.

All of the tests for outside causes have been coming back negative, as anticipated. When I said I was being test for Hepatitis, I should have specified viral Hepatitis. I have learned that hepatitis is a generic term for liver injury and inflammation. Drug induced hepatotoxicity (pronounced (hep′ă-tō-tok-sis′i-tē), and referring to the capacity of a drug or other agent to induce liver injury) is also referred to by the acronym DILI or drug induced liver injury. It is relatively uncommon, “DILI in the case of any single drug is thought to occur approximately in one per 10 000–100 000 treated patients.”  (from Pub Med Central). However, I wonder if that statistic is pertinent to clinical trials. Phase I of a trial, such as the one I am enrolled in, is to determine at what level a drug can safely be administered, and to do so through dose escalation. Although my ALT/AST were significantly elevated, the fact that my liver function was never compromised is an important distinction, not just for me but for the the trial itself. Severe DILI is defined as liver failure or death, two bullets I obviously dodged. However, it would seem that the careful monitoring I received was not misplaced, as evidenced by this article in Medscape about drug induced hepatitis.

Although I would like to go back on trial as soon as possible, I have some trepidation as well. There is the possibility that when the LDK 378 is reintroduced, the scenario may be repeated. Of course, the only way to find out is to try, and I assume I would be monitored even more closely at rechallenge (the opposite of dechallenge, or holding of the drug).  The FDA has published a Guideline For Industry that specifically addresses the issues surrounding DILI in a clinical trial setting, should you be interested in the specifics.

In the big picture, it is not so very important, but I’m sad to say that my drinking days might be over; I can’t even look at a glass of wine anymore. And I had such a talent for (the wine tasting) and sublime appreciation of. Oh well. I actually awakened in a bit of a cold sweat last night because I dreamt I’d had a cocktail.

So, in conclusion, I came out on the good end of a bad week. I am both highly encouraged and deeply anxious about where we go from here. And I will keep you posted.

Change of Scenery

Thanks so much to everyone who left comments on the previous post. As you can see from the photo, my little bump in the road got a bit bigger and I am writing this from a hospital bed.

Shortly after I published the previous post, I got a phone call from Dr. Shaw with the results from the local lab. My liver enzymes, rather than going down, had now risen to more than four times their level on Monday. Essentially, my liver was being poisoned. There isn’t an antidote for hepatotoxicity, but Alice (Dr. Shaw) wanted me to come in for monitoring. Significantly elevated liver enzymes (ALT/SGPT and AST/SGOT) are a sign that rapid cell death or injury to the liver has occurred (as the cells die they lyse, or break apart, and release enzymes into the blood stream). However, even a severely injured liver can maintain function. My circulating levels of bilirubin and alkaline phosphatase were both within normal limits, which was reassuring. In the case of actual liver malfunction, they would be elevated as well. However, should the ALT/AST continue to rise, function could be affected as well.

So, off to the hospital I went. Initially I was assigned to a double in an acute care wing. Dr. Shaw checked in and then it was time for some tests. Around 10 pm my liver enzymes were tested once again and they were slightly lower than the one that morning but still quite high. I had a chest x-ray as I was still coughing (and the levaquin was now being held as well) but it came back clear for pneumonia. I was poked and prodded and asked if it hurt until it finally did. I was given an ultrasound of my abdomen, which showed no lesions (thank goodness for that). And, just to rule out anything else that could have instigated the elevation, I was tested for everything under the sun that could affect liver enzymes. Hepatitis, HIV, Epstein-Barr, drugs and alcohol (just in case the patient wasn’t disclosing!).

My roommate was a lovely woman, but anything other than a private room in the hospital is just really hard. Two people, both sick but generally not in the same way, a shared bathroom and a very modest space full of apparatus that is often beeping loudly, a parade of doctors, nurses and visitors as well as the inability to not hear everything that is being said and happening on the other side of the curtain which divided us. It is really not conducive to sleep or healing.

Fortunately, by late Friday, a room had opened in the Lunder building. It is a new wing of Massuchetts General Hospital which is devoted to cancer patients. It is located directly adjacent to the Yawkey center, where I receive my outpatient care. All the rooms are private, spare and modern  and graced with large windows as well as pull out couches for visitors. It’s really nice.

So, that’s where I’ve been hanging out. Aside from a twelve hour period of diarrhea (unrelated to the liver, so more tests) I have felt under the weather, but not too bad. Each day my enzymes have been a bit lower; at first the change was incremental, but the downward pace is increasing. My appetite is coming back as well, and I’m starting to feel restless (a good sign).

It’s now Sunday. Half an hour ago I was handed my discharge papers. My ALT is still in the triple digits, but at this rate, I should be back to normal soon. Once home, I will resume the levaquin (now felt safe to reintroduce) as my chest infection has lingered. On Tuesday I’ll be back in Boston for more labs, a chest CT scan and a quick meeting with Alice. The big question will be, where do we go from here?