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.

Saturday, October 30, 2010

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.

Thursday, October 21, 2010

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.

Thursday, October 14, 2010

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…

Saturday, October 9, 2010

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.

Sunday, October 3, 2010

The latest Viral Load Results – Sort of

When I checked the mailbox Saturday, I saw the envelope with my latest test results. Two weeks ago when my last test numbers came in the mail, I did some serious magical thinking. I implored nature to be on my side, I beseeched luck and karma and I chanted to myself all the way into the house. This time, the site of the envelope made me queasy. I was so close to undetectable last time and want so much to finally be undetectable with this test, that fear was the main emotion I felt. I want good news. I want the prize and I don’t know how I will react if the numbers don’t back up what I want to happen.

I take the envelope into the house, tear it open and scan down the page past the white and red blood cell results to the RNA quantitative numbers. There I see this statement: “test cancelled, coding error, resubmitted to LIS.” I have been either in the RO5024048 study or in Standard of Care chemotherapy for 10 months. During that time I have had over 40 separate blood draws with hundreds of tests done on the blood. Never during all that has a test failed, been cancelled or had faulty results. But this week, when I may see the result I have been waiting for since I got bounced out of the study by the viral breakthrough, something was wrong with either the blood or the test. To say it is torture would be an insult to those who have actually undergone torture, but mental agony, yes indeed.

I will call my nurse on Monday to check if the test was redone and there are any updated results, but I have the sickening feeling that I won’t see any updated viral load numbers until the results of the test scheduled for this coming Wednesday come back in a couple of weeks.

When you are in chemotherapy your focus tends to narrow. Test results become the mileposts by which you judge your progress. They are regular points of data that you use to chart the fight against your disease. You have cycles of drug taking, cycles of side effects and cycles of results that mark your life. Missing test results have a serious psychological effect on your treatment in the same way that missing drug doses have a serious physical effect. This was the week I was going to celebrate (or weep with fear that the chemotherapy wasn’t going to be effective). Instead I am left hanging for another two weeks until I find out whether it’s hope or fear.

On the bright side, the Giants won the Western Division today and are going to the post-season. So life really is good after all…

Friday, October 1, 2010

The End Of The Season – Baseball, That Is.

Fantasy Team Disappoints, Actual Baseball Exhilarates


The Vincent Black Shadows, a fantasy baseball franchise operated by your correspondent for the past 25 years in five different fantasy leagues in three different cities in two different time zones, are limping to a sixth place finish in the Tri-Tip League of Santa Barbara. It was a year that saw the team crippled by injuries, players traded out of the National League and players underachieving due to sloth, pigheadedness and the insistence of playing while injured.

The Shadows pitching staff was particularly disappointing. Young pitchers failed to develop (Paul Maholm, Chris Volstad). Veterans regressed (Aaron Harang, David Bush). Speculative signings failed to pan out (Sean Gallagher, Sammy Gervacio).

The position player side of the roster entered the season weak in power hitting. My plan to leverage my excellent farm system (Starlin Castro, Jose Tabata, Devaris Gordon) as trade bait to acquire sluggers from other teams was scotched by the unexpected early promotions of Castro and Tabata to the big leagues. Adding to my loss of trade leverage were injuries to two key players (John Baker, Mark DeRosa) and the trade to the American League of another (Conor Jackson) leaving my team with holes I could not fill.

Even with this bad luck, I was still in the hunt until late July. I was unable to negotiate the needed trades however, and even my prescient signing of new Milwaukee closer John Axford and the late season additions of Kevin Corriea and Joe Blanton could not generate the necessary momentum for a run at the money. The foundation for next year’s team is very solid, but it is cold comfort indeed here at the tail end of my third year in a row finishing out of the money.

I like to think that the brain fog produced by Hep C and interferon contributed to the Shadow’s disappointing season by impairing the decisions made by the team’s “baseball people.” In fact, now that I think of it, I went symptomatic right about the time that the Shadow’s began their decline…

Major League baseball, on the other hand, has been a delight. My old home team, the Twins are in the playoffs, the Texas Rangers managed by one of my favorite people in baseball, Ron Washington are in the playoffs and Your San Francisco Giants, with a win tonight against the Padres, will win the National League Western Division Championship. The postseason is almost upon us and I have several rooting interests and a friend who has scrambled around and secured tickets.

I am optimistically awaiting my latest viral load results, and the Giant’s game is starting up on the TV and life is good enough for now…