I am a 57-year-old white American male infected with Hepatitis C. I am involved in a controlled medical research study by Roche Pharmaceuticals of an experimental Polymerase Inhibitor (RO5024048 also known as RG7128) drug therapy for the virus. This document is the story of my illness and the experience of treatment. My lovely and pretty damn wonderful wife will be contributing her take on the experience as well.

Wednesday, February 29, 2012

Long-Term Side Effects - The Thyroid Gland

The interferon and ribavirin chemotherapy has been over for eight months. That seems to be an appropriate amount of time to examine the long-term side effects of the therapy. In an early post, (which you can get byclicking here), I listed all the side effects of both the polymerase inhibitor test drug RG7128 and the standard interferon and ribavirin chemotherapy. It is a long list. While some of the side effects are relatively mild, a significant number of them are potentially very serious.  The one on which I'd like to concentrate today is the effect of the therapy on the thyroid gland.

In the initial literature handed out at the beginning of the experimental trial, it was noted that the functioning of the thyroid might be affected and in some cases the effects might be permanent. The wording of the literature led one to believe that while thyroid function might be affected during the trial, there was a good chance that the thyroid would return to normal after the interferon and ribavirin was stopped. At about the 6-week mark of the trial my thyroid function numbers began to deviate from normal. The level of TSH in my blood (which stimulates the thyroid when it’s activity is low) began to rise. During the next few weeks it tested at 10 iu/ml and then at 25 and 30 and then finally at 55. This level indicates that thyroid gland is not functioning remotely normally. At this point I was put on levothyroxine and within about 3 weeks my thyroid level was back to normal. I stayed on the levothyroxine for the rest of the time I was in the experimental trial and continued it through the transition to the standard of care interferon and ribavirin chemotherapy. I was on that program for an additional 13 months and I stayed on the thyroid medication the entire time.

When the standard chemotherapy ended I talked to the gastroenterologist at Kaiser who runs their Hep C program about procedure that I should use to wean myself off the thyroid medication to return to normal thyroid function without medication. In reply to this question, he replied that in his experience the standard of care interferon and ribavirin combination usually burned out the thyroid gland and I would most likely be on thyroid medication for the rest of my life. Knock me over with a feather. This was not what I had assumed to be the case nor was it the case that was presented in the initial discussion of side effects at the beginning of the experimental trial. I have no idea what my reaction would have been if the potential thyroid effects had been described in that manner. I may have decided to go through with the trial anyway and may not have, but I do wish that the information had been stated in a very clear and concise manner. It leaves one with the feeling that the research doctors know damn well that the thyroid side effects are likely permanent, but that it is not to their advantage to say that. If you tell someone that there is an interferon-based regime that, with the addition of an experimental drug, will have a 75% chance of curing hepatitis C but will result in the permanent sacrifice of the thyroid gland, how would they find enough subjects for their drug trials. Would anyone short of those whose life was truly in danger because of the effects on the liver of hepatitis C be willing to go through an interferon-based therapy?

If the choice had been put to me that way, I certainly don’t know what I would have done.  I knew then that my liver was not in bad shape. My liver functions were abnormal and my viral load was very high but my liver itself was not badly swollen and did not exhibit heavy scarring. I might have just said let's wait till newer therapies become available, though at the time it was not known that any drugs would be coming through the pipeline soon that did not involve using interferon and ribavirin as well. I don't know what I would have done but I wish I had better information when I made the choice.

Not wanting to believe that I was one of the people whose thyroid was burned out, I decided to wean myself off the levothyroxine and see what happened. I started out by taking my normal dose (100 mg) for the first two months after the end of the therapy. At that time I reduced my dose to one half (50mg) for the next month and then reduced it further to 50mg every other day for another 6 weeks. I stopped taking the levothyroxine for the final 3 weeks before my six-month viral load test. I asked my doctor to test my thyroid enzyme levels at that test because I had been attempting to wean myself off the levothyroxine. He agreed and when the test came back my TSH hormone level was at 53 indicating that indeed my thyroid was not operating and may never operate again. So I am back on levothyroxine and probably will be for the rest of my life. It's an uncomfortable feeling to know that your health will always be dependent on your ability to secure a supply of a particular drug that provides an essential ingredient for your survival but it's certainly not unique to me. People with diabetes have had to deal with this for a very long time, as have people with AIDS and folks with other diseases that I am no doubt forgetting about. It's just one of those things.

But it's something to consider if you are in a position of entering any therapy or drug protocol in a drug trial that uses interferon. Whatever benefits you are going to be getting from the use of interferon will most likely come at the cost of your thyroid gland. Weigh it carefully. It may be the lesser of two evils and you may decide to go-ahead with the therapy but always remember the costs that will be exacted.

Wednesday, February 8, 2012

Six Months Later…Viral Breakthrough

I recently had six month after treatment blood test to determine if I achieved a sustained viral response or SVR. The results came back today and the Hep C virus is back. My viral load is currently at 1 million IU/ml. This completely sucks. 18 months of interferon and ribavirin including 5 months of an experimental polymerase inhibitor RG7168 aka RO5024048 that produced the side effects of weight loss, depression, inability to concentrate, lack of energy, memory going to hell, anemia, and I'm sure others, that the memory problems prevent me from remembering; all of this to achieve nothing. It is getting hit by the million pound shit-hammer all over again.

 I knew at the beginning that the traditional therapy only resulted in a 45% chance of clearing the virus. So when I had the chance to get into the trial of the RG 7128 aka RO5024048 polymerase inhibitor which, in early-stage experiments had demonstrated a rate of clearing the virus of up to 75%, I jumped at it. I'd hoped that the experimental drug would clear the virus. Even after the viral breakthrough that resulted in my expulsion from the test group I still thought that transitioning to standard therapy after the initial success of the experimental drug might give me a small leg up on clearing the virus.

Perhaps the fact that it took 12 weeks for the traditional interferon/ribavirin therapy to bring my viral load down from only 40,000 IU/ml to clear should have tipped me off. Maybe it should have shown me  that the strain of virus that I have would be resistant to my own immune system and traditional therapy and I would perhaps be more likely not to clear the virus then to succeed, but no one wants to face that possibility. When you have already been in a process for six months and you've already faced the side effects and found that, to a point, you can handle them; and you believe you have a chance of clearing the virus; and you don’t know what your health insurance is going to be like in another year or two or whenever a new therapy might come online; and the fact that you have insurance now; and you’re stubborn and you're optimistic; it all puts you in a mind to say I'm going to see if sticking this out will succeed in bringing me to a sustained viral response and a cure.

Well it didn't. So in a sense I look at the last two years of my life, the 18 months on the therapy and the six months beginning to recover from it until the day of the test, as being wasted. I did not get much accomplished during those two years. While I was able to do very good things at work (including expanding the scope of my operation, systematizing and streamlining all of the processes, integrating a part-time person and training them in handling the basics of the operation, and increasing sales and average of 25% per year), that is cold comfort. Just doing that, just functioning on a day-to-day basis and going to my job eventually took so much energy that it left little time and little energy for any part of a personal life. My work and efforts as a sculptor were minimal, my ability to do things with my friends and family were cut way down by the fact that it was exhausting to do anything for very much time at all. It all infuriates me even though I knew that it was only a 50% chance at success. I don't think anyone ever enters a situation like this thinking that they're going to fail and I certainly didn't. The fact that the therapy did not work leaves me feeling somehow cheated. It's not rational, but there it is. You feel that if you spent that much time, that much energy (or lack of it) invested that much hope and effort, something better should have happened. It didn't and I feel somehow empty.

All that being said, on the good side all my liver functions are normal. My doctors tell me that the results that they're getting from the liver tests would indicate that the time that I spent clear of the virus during the therapy, (which totaled about 12 to 14 months out of the 18), allowed my liver to begin to heal itself. The swelling is reduced. It is functioning well and I have bought additional time with a healthy liver. I also learned that I can handle the therapy. I learned that the side effects I got with the standard interferon ribavirin  chemotherapy and with the RG7128 are ones that I can manage. I know that a lot of people have a much more difficult time than I ever did during the traditional therapy. There are people who are so exhausted they can barely move; people whose anemia is frighteningly intense; people who have much more severe depression; people who lose even more weight than I did; people who have even less energy and people whose cognitive facilities and memory decline even further than mine. I realize that the ones who have it far worse than I did must feel even more empty or betrayed or depressed when they find out that it didn't work. Because as difficult as it was for me, if I had gone through even 12 months of the sort of difficulties that others with this disease undergoing the same therapy went through, I don't know if I could ever face doing it again.

 I'm sure at some point I will do it again. I don't like the idea of managing this disease. I don't like the idea of having something in my body that is gradually destroying my liver, breaking down my cognitive functions and creating in the long run a less energetic less mentally sharp individual. I don’t like the possibility of developing serious liver problems that might include liver cancer, cirrhosis and result in the need for a transplant. Though  my doctors told me that given my liver results I am the sort of person who is more likely to die with hepatitis C than from hepatitis C, I don't want to have it at all. The idea that a lifeless particle of protein wrapped around some DNA is working its way through my body destroying my liver doesn't fit my disposition. So I will try again at some point.

 I don't know that I will ever try interferon therapy again. It is extremely devastating and I don't know if I can face it even though I do suffer it better than many other people. There is a tremendous amount of research going on and a lot of that is oriented towards non-interferon drug combinations to attack the virus. There's a lot to look forward to and I know that I'm in good shape to see where it leads.

It's still depressing, it still sucks but you buck up and handle it the best you can. Even though I've been whining for most of this post, I know that my life is a hell of a lot better than a lot of other people in the world and especially a lot of other people with Hep C. Besides, Spring Training is right around the corner and how can you stay depressed when pitchers and catchers report in only six weeks,