Science Café About Hepatitis C Research

San Francisco has a thriving science and nerd community. A symptom of that is the wide array of science events that occur throughout the Bay Area every month. One of them is a monthly series titled “Science Café” in which a scientist or two is inveigled to come to a local café and talk for a few hours about their area of expertise. The most recent event was about Hepatitis C.

The Atlas Café was the scene and the scientists were Dr. Melanie Ott of the Gladstone Institute who researches the reproduction cycle of the Hep C virus and Dr. Todd Frederick a Hepatologist at the California Pacific Medical Center who treats Hep C patients. As a disclaimer I must mention that Dr. Frederick has examined, palpated and prescribed for me as part of the Polymerase Inhibitor study I was in.

Dr. Frederick gave an overview of the scope of the Hep C epidemic and the nature of current treatments available to combat it. He talked about the new protease inhibitors Telaprevir and Boceprevir that are awaiting FDA approval to be used in combination with interferon and ribavirin. He also gave a hint at possible future therapies using polymerase inhibitors with interferon and ribavirin and the possible combination of polymerase and protease inhibitors with ribavirin to create a treatment regimen that does not use interferon.

Dr. Ott gave us a basic yet thorough crash course in the reproductive cycle of the Hep C virus. She revealed its dependence on fat molecules in human cells and the promising area of research involved in using fat disabling compounds to interfere with the ability of the Hep C virus to reproduce itself. She also had a very cool animation that illustrated the reproductive cycle of the virus. She was quick to state that this was still basic, in the petri dish research and many years away from demonstrating efficacy in living organisms. It was fascinating stuff and the crowd of 30 was intent throughout both presentations.

A few of the questions asked in the Q & A were about the new compounds being developed and particularly about the issue of deciding whether to treat now or wait for new developments. Dr. Frederick clearly attempted to be balanced in his answers, but as a doctor involved in clinical trials of promising new compounds he is really exited about the possibilities of the new treatment combinations and he showed a bit of a bias towards waiting for new developments.

I respect Dr. Frederick’s viewpoint a great deal, but I think if you are seriously considering entering treatment, you need to consider a wide range of factors beyond the simple consideration of treatment outcome percentages. The condition of your general health, the condition of your liver, the amount of impact the disease is having on your quality of life, your family situation, your housing situation, your work situation, your insurance situation, your financial situation, the quality of support you can expect, all of these are important factors to consider in your decision. We still don’t know when the new drugs will be approved, how quickly they may be included in insurance company covered drug rosters, and how much they will cost (though we do know they will be expensive). So think it all through thoroughly and carefully before making a decision. While the future may be so bright we gotta wear shades, the shades might be very expensive and the future a bit further off than we would wish.

Personal Evidence of Cognitive Deficits from Hepatitis C Treatment

I am writing this piece having finally managed to tear myself away from the television after watching almost 90 minutes of the Adam Sandler vehicle “You Don’t Mess With The Zohan.” If that is not evidence enough that 46 weeks of treatment have eroded my mental capacities, let me add this nugget: I had to get up, go downstairs, turn the television on and check the listings to remember the name of the movie. Having walked away from the TV not 3 minutes earlier, I could only remember that the movie had the word Zohan in the title but could not recall the complete title.

In the past 6 months of treatment, my critical capacities have deteriorated to the point that I have descended from watching “Celebrity Rehab” through “Jersey Shore” and “Basketball Wives” and now am watching, and more embarrassingly being entertained by, Adam Sandler movies. I have 26 weeks to go in my Hep C chemo regimen, what will I be watching by next June, “Jackass 7, Stupid Geezers in 3D”?

The sad part is that I cannot help myself and neither it seems, can other Hep C chemo veterans. Almost everyone I have talked to about their treatment has admitted that the same thing happened to them. The lucky ones were finally so tired and concentrationally challenged they could not even muster the energy to pay attention to television and just sat staring into space. I suspect that would be preferable to Rob Schneider, Johnny Knoxville, Dane Cook or whatever else might be passing in front of my eyeballs by the end of this.

It is disconcerting to think that this result has a tiny chance of remaining permanent. While I might end up being perfectly happy as a drooling idiot for the rest of my life, I suspect my wife would find that less charming.

But, looking on the bright side, when I finally stop the interferon I can document in painful detail the increase in brain function, the gradual increase in my boredom threshold and the return of my memory. Given that I’ll be approaching 60 by the time I fully recover from all this, I wonder how I will be able to tell if my memory is back or not…

I admit that all of this is anecdotal evidence from a small set of treatment-experienced individuals and does not attain the level of statistical validity, but it is nonetheless disturbing. I’m not sure what would happen if I started to bug my wife to come with me to the latest Adam Sandler classic on opening night.

Managing Serotonin Update

It’s been just over 4 weeks since I cut down on the drugs that affect the serotonin levels in the brain. I was taking trazadone for sleep, tramadol for pain and daily doses of Celexa for depression. I cut out the tramadol and the trazadone and, after consultation with my hepatologist Dr. Bzowej, replaced them with Ambien and Vicodin. The results have been significant.

I have noticed that I am physically calmer. My hands are steadier and the random muscle twitching I have been experiencing has receded a bit. I still have all the hyperactivity behaviors I’ve had all my life (leg bouncing, pacing, etc.) but I am not as physically tense and tight as I was 4 weeks ago. My teeth-clenching and grinding have both subsided and the tendency to get caught in negative mental feedback loops (or to put it another way, become obsessed with other people’s irritating behavior) has also declined. Not to be continually catching myself thinking about other people and their foibles really reduces the stress load.

Among the downside to the change is that I am now using Vicodin for pain. Tramadol was relatively mild in its mental effects compared to vicodin. The days I have to take two doses to relieve the aching and allow sleep leave me loopy while I’m taking it and groggy the next morning. Given that serotonin overload can result in seizures and occasionally death, I’ll deal with vicodin’s side effects, it’s just that losing even more mental acuity while I’m taking it means I have even less to work with.

Ambien works differently as well. It is not as strong as trazadone. That means that I don’t wake up groggy, but I also wake up much more during the night. Trazadone would generally allow me to get at least one stretch of 3-4 hours of sleep during the night. The ambien puts me to sleep more gently but also not as deeply and I generally sleep for no more than 2 hours at a time. I wake up feeling rested so it is apparently having the desired effect, it just accomplishes it differently.

The change in medications has done me good. This reinforces the fact that you have to pay close attention to your own physical state and close attention as well to your drugs, their doses and their interactions. Don’t be afraid to talk to your doctor about any symptoms you think may be related to any of your drugs. They can’t help you if you don’t talk to them. Make sure that you get your questions and concerns are answered in any meetings you have with your doctors and nurses.

Now that my mental state is calmer and steadier and my energy is returning after the emotional roller coaster of the San Francisco Giants World Championship drive, I hope to have more frequent postings. Thanks to all of you who have commented and offered support. I hope the rally thong ends up in Cooperstown…

Memory Deficit Side Effects May Be Permanent

There was a guy I knew years ago who had the talent of entering a conversation about almost any subject with the line, “let me tell you a story about that.” Strangely enough, the story was relevant to the subject an uncanny amount of the time. I don’t have that same talent, but that won’t stop me from starting off with a story.

The day that I got the news that my viral load was undetectable or “negative” in the parlance of the hepatology folks, I wrote an entry about the motivation that gave me to pay special attention to my drug dosing regimen so as to give myself the best chance to succeed at having a sustained viral response at the end of treatment. Motivated though I was, I forgot both my evening Ribavirin dose and my evening injection of interferon on that very day. This was not disastrous as I had already taken 600 mg of ribavirin in the morning and I was able to give myself the interferon the following day. Nonetheless, it shows the power that interferon brain fog has to confuse even in the face of sincere dedication.

The following week I had my regular appointment with my hepatologist Dr. Bzowej. We discussed my test results, my general state of health and how I was reacting to the medications I was taking. I went over the various physical reactions I was having to the drugs and how those reactions had changed over time. She then quizzed me about my mental state. I told her that my memory had deteriorated quite a bit over the course of treatment and that my ability to concentrate and solve problems had also taken a hit. These are expected side effects of the interferon and ribavirin drug combination, but Dr. Bzowej had some new information about them that is quite disturbing.

The memory and cognitive deficits that Hep C treatment inflicts on those who are undertaking it have been believed to be temporary. When the patient stops taking the drugs, those side effects gradually disappeared and the patient returned to the same mental acuity they had before treatment began. This is apparently not always the case. Dr. Bzowej related that in the past year, she has had two patients whose symptoms have not improved. Their memory and concentration problems have remained over a year after no longer taking interferon and ribavirin. She is concerned enough that she referred me to a neuro-psychology specialist for a set of tests to determine my current memory and cognitive abilities. She will then have me tested in anther 3 months to check whether there has been further deterioration and if so, what course of action we should take.

This scares the crap out of me. The one thing I have always been able to rely on is my brain. I have neither dazzling good looks nor great athletic ability or physical strength. I have some amount of personal charm, but certainly not enough to depend on for a living. Nor do I have vast amounts of physical or moral courage. What I do have is a good brain. I have intelligence, creativity, the ability to learn new skills relatively quickly and the ability to solve problems. This has always been the rock I could depend on, and if it crumbles, I don’t know where it leaves me. A pile of sand on the beach maybe; certainly it changes who I am and what I can do.

The same applies to anyone else considering entering treatment. Talk to your hepatologist about this issue. Ask if it is possible to be tested for memory and cognitive function before treatment begins to establish a baseline for future reference. While in treatment keep your doctor informed of the symptoms of memory and concentration loss. You have to decide if being cleared of the Hep C virus is worth the small possibility of permanent brain function damage.

I’m still glad I entered the study and am now in standard treatment, but I don’t want the price to be permanent memory disability no matter how small the chances of that happening.

Undetectable

There is a certain sort of mild agony that accompanies waiting for medical test results. You want to know the results, but at the same time you don’t want to learn anything negative. It is a feeling of “please let me know the results as quickly as possible, but only if it is good news.” If the results are delayed, the tension slowly increases until you don’t care what the results are; you just want to hear something definite. I was in that holding pattern until yesterday when I finally got the first viral load numbers I have seen in a month. The tension turned to relief when I learned I was back to undetectable.

Finally, after 16 weeks of Standard of Care chemo, I am officially back to where I was after 6 weeks of the RO5024048 study. I have definitely been undetectable (under 43 IU/ml by this test) since October 6th. I may have been undetectable since September 23rd, but that was the test the lab screwed up. This means that, among other things, my liver is getting a break from the tissue damage that occurs while fighting the Hep C virus. It can begin to heal and regenerate once again.

It also means there is now a date certain (as the politicians would say) for the end of my Standard of Care chemotherapy. The hepatologists at California Pacific Medical Center (CPMC) continue interferon and ribavirin therapy for 36 weeks after the patient reaches undetectable level. That means that June 15th, 2011 will be the end of treatment. Now I can start crossing off weeks on my calendar (or maybe I can start carving marks into my desktop for each week completed) until it is over.

This is all based on the fact that I stay undetectable in each test from now until then, but I have even more motivation now to adhere as closely as possible to the “Best Practices” of the chemo regimen. (Sorry for the corporate terminology in the last sentence, but I was at our strategic planning staff meeting today where I was bombarded with bureaucratic mumblespeak up to and including “creating cross-functional workgroup plans”)

I have a deadline. There is real evidence that the interferon and ribavirin regimen is working. I will hold these facts in front of me like talismans whenever the night sweats get too wet, nothing seems worth eating and getting up the steps of the stadium to the cheap seats leaves me exhausted. It is working and there is an end in sight. It was worth the wait to hear those things.

Managing The Serotonin Complex

My previous post discussed the problems I have been having because I am taking Celexa, Trazadone and Tramadol to manage side effects of my chemotherapy. I had a scheduled appointment with my hepatologist this past Friday and decided to bring these issues up at the meeting.

That plan was derailed from the start. When I got to the doctor’s office, my appointment had been cancelled. It was irritating as hell, but they did immediately contact my nurse practitioner Alex who called in the overall Hep C treatment nurse Tammy for a three-way consult. I explained my symptoms and my worries about serotonin overload. Tammy agreed with me that my symptoms could be some level of serotonin syndrome and she and Alex both said I should stop the Tramadol. I told them that the only effective means I had of dealing with the muscle pain I get each injection cycle was to take 800 mg of Ibuprofen every 4 hours. I said it worked fine, but that I had been told it was bad for my kidneys. They agreed but said that in the hepatology department they do not prescribe any opiate-based painkillers. I would have to talk to my primary care doctor in order to get anything prescribed. This sets me up for a great meeting with Dr. K to engage in some classic drug-seeking behavior. I need that stress like I need another hemorrhoid.

I also told them I wanted to change from Trazadone to something else for sleep. They were both resistant to that suggestion. Apparently Trazadone is prescribed along with Celexa and other antidepressants fairly commonly and without problems. I explained that my nervous system is sensitive to drugs and perhaps we should cut back to only one serotonin reuptake inhibitor. They told me that we should eliminate one at a time. Not a bad idea, but then they don’t feel as jumpy as I do.

That was five days ago and it has been a nasty five days indeed. I decided to stop the trazadone as well as the tramadol to try to get my serotonin levels done more quickly. The first 3 days were especially rough at night. My legs were so twitchy that I had to keep getting out of bed to walk around and tire them out. When I got back to be, I had a ten minute window to fall asleep before the twitching would start again and I would have to start pacing, It was a great deal like the symptoms described in this post, but they lasted longer and were more intense. I managed to get about four hours of sleep a night.

The past few days have been better. I have less general jumpiness, irritability and nervousness during the day. The nights are still difficult, but I have been able to get five to six hours of sleep. I am going to try some over-the-counter sleep stuff of some kind if this goes on much longer.

I think I made the right choice to get off the tramadol and the trazadone, but I certainly wish I had a better idea of how long it’s going to take for my body to settle down a bit. I have dealt with restless leg syndrome all my life, but if this goes on much longer I’ll need stronger drugs than celexa to keep me sane…

Minding Your Drug Interactions

Among the disadvantages of being in a drug research study is the tendency for discontinuity in your medical care. The RO5024048 Roche study that I participated in was run by Dr. Natalie Bzowej. It was administered by the Hepatology Center at California Pacific Medical Centers (CPMC). CPMC is a first rate institution and they do cutting edge Hepatitis C research. The doctors are excellent, but as is true with specialists everywhere, they are busy people with many patients. When I screened for the study, I was examined by Dr. Frederick. For early symptoms of rash, sweats etc, I was examined by Dr. Merriman. When I had difficulty with pain issues I was examined by Dr. Bonacini and prescribed Tramadol. Later, when I was having trouble with sleep, I was examined by Dr. Frederick and prescribed Trazadone. When depression issues cropped up, I was examined by Dr. Bzowej and prescribed Paxil. and added Ativan for use as needed. After I reported difficulties with the Paxil, I was seen by Dr. Frederick again and he changed the antidepressant to Celexa Finally, my thyroid function was affected by the research meds and I was put on Levothyroxine by my primary care doctor.

Over time, this can add up to a significant number of medications creating their own set of interactions with each other that have to be carefully attended to. This is something that you should not be leaving solely to the doctors treating you. All the doctors in the hepatology center work on the same team. They are all involved in doing research and, to the limits imposed by patient and study confidentiality restrictions, they communicate with each other and share patient information. However, each doctor has preferred medications they are familiar with and prescribe regularly. This creates a situation in which each doctor is thoroughly familiar with certain meds and they may not be conversant in the effects and interactions of meds preferred and prescribed by the other doctors. You have to do your own research on the drugs you are taking and the potential interactions between them all. I found the drug interaction database at drugs.com to be particularly helpful. If you find something, contact your doctor and get their response. If you feel you need to change drugs, tell them. Keep at it until you get answers that satisfy you.

In my case, I was prescribed tramadol, trazadone and celexa. All have the effect of inhibiting serotonin reuptake in the brain. While this is a good thing for combating depression, if it results in an overabundance of serotonin in the brain, it can cause serious problems: irritability, confusion, tremor, stronger reflex reactions, sweats and potentially even seizures. I do not think these would have been prescribed together if all my symptoms had manifested at the same time. But as each was prescribed for a symptom that was occurring at separate times in the study, I ended up taking them all. There are days when I have to take all three and it is on those days that I have been noticing an increase in my some of my symptoms.

I have increased irritability, a general increase in physical tension and in activities like rubbing my hands, pacing, grinding my teeth, etc. This is all symptomatic of serotonin syndrome which I thought I experienced a few months ago. I am seeing both my primary care doctor and my hepatologist this week and will bring this all up with them both. I would like to see another painkiller substituted for the tramadol and perhaps another sleep aid substituted for the trazadone. I am not sure which way the doctors will want to go but I am tired of feeling this way and need a change.