Hepatitis C Treatment: The Big Sleep In The Rabbit Hole

Going through treatment of Hepatitis C, I suspended reality. 

My world became a rabbit hole.  More like a depressed Bugs Bunny than Alice.

The first on-screen appearance of Bugs Bunny, ...
The first on-screen appearance of Bugs Bunny, from an unrestored version of the cartoon. (Photo credit: Wikipedia)

Only my husband Spanky, the psychiatrist and the research nurse could check on me.  But frequently I pulled the hole in on myself and stayed there.  It was kinda weird.   I felt safe from others but not my crazy mind.  I couldn’t close the rabbit hole fast enough to keep out my mind.   Sometimes I felt like I was watching the world through a window but  I couldn’t remember what happened that day.

Memories of coming out of a bar when the sun is still bright, eewww.

Twice stolen from Edvard Munch

Twice stolen from Edvard Munch

malavula.blogspot.com

I used to wonder if other study patients felt the same as me.  I would watch in the waiting room.  But they weren’t giving up their secrets.  Each traveling with his own rabbit hole.

Rabbit Hole Urban Dictionary
Alice in…Metaphor for the conceptual path which is thought to lead to the true nature of reality. Infinitesimally deep and complex, venturing too far down is probably not that great of an idea.
An allusion to Lewis Carroll’s Alice in Wonderland. To go “down the rabbithole” is to enter a period of chaos or confusion.
Or to take acid, Deb
…….
Then the study ended.  As drugs began to leach out of my body, I felt like I took a year-long nap.  Only I wasn’t asleep.  I was waking from a little tiny world.  Like a newly released guest of the penal system or someone from the space station, I heard about stuff while in my pseudo-sleep but hadn’t really grasped it.  Politics, friends, life skills, I had to catch up on it all. This is more difficult than you think, trying to get past all the celebrity crap. Who “gets” celebrity crap?  I don’t but somebody must or it wouldn’t be ubiquitous.
Sometimes I want to crawl back down the rabbit hole.  During those times, I hang out in our guest room, my home during treatment.  It’s comforting in a psychiatric kind of way.  It took months to feel free of that need,  about four half-lives*  When I can’t sleep I still go in there.  It is normal to lie awake all night in the rabbit hole.
 I’m thinking of painting the rabbit hole room lavender (I don’t like lavender) or getting a new bed (I like the existing bed).  Dismantle the tangible rabbit hole.
*A half-life, t1/2, is the time it takes to remove 1/2 of a drug from your system.  To approach 100% drug removal takes about six half-lives.

A biological half-life or elimination half-life is the time it takes for a substance (drug, radioactive nuclide, or other) to lose one-half of its pharmacologic, physiologic, or radiological activity. In a medical context, the half-life may also describe the time that it takes for the concentration in blood plasma of a substance to reach one-half of its steady-state value (the “plasma half-life”)

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The Hepatitis C Screen Door Swings Two Ways

My father-in-law wanted Viagra.  He wouldn’t shut up about it.  My mother-in-law finally said “Then what?  You’re not getting on me”  eewww, the visual for me….

So we screen for Hepatitis C, then what?

Attention Baby Boomers: The Centers For Disease Control (CDC), the group that tracks bird and swine flu, is thinking about screening you for Hepatitis C.

Hepatitis C is particularly dangerous because it is a silent killer. It can live for decades in a person’s body, slowly destroying the liver, while causing few symptoms,” said Dr. John Ward, director of the CDC’s division of viral hepatitis.

The new guidelines are expected to identify more than 800,000 infections, prevent 100,000 cases of cirrhosis, prevent more than 50,000 cases of liver cancer, and save more than 120,000 lives. Hepatitis C is the leading cause of liver transplants in the United States.

The relatively inexpensive blood test is “a small investment now for a big benefit later,” Ward said.

The CDC believes routine blood tests will address the largely preventable consequences of the disease, especially in light of newly available therapies that can cure around 75 percent of infections.

The field has attracted broad interest with two new hepatitis C drugs, Incivek from Vertex Pharmaceuticals Inc and Merck & Co’s Victrelis, reaching the U.S. market in the past year.

Sorry about the blur, link at bottom if you are interested

Should we screen for Hepatitis C in patients over 50?  There is no vaccine, the standard treatment of Interferon/Ribavirin is about  $60,000 and the eradication rate about 40-50% in the most common genotype (1).  Adding  Boceprevir (Victrelis) is $1,000 a week (x 24 weeks = $24,000). Telaprevir (Incivik) is $4,100 per week (x 24 weeks = $98,000).  So treatment =  $80,000 to $158,000.  They must be really proud of Telaprevir.  At that price they may have to keep it.  All of this assumes 24 week treatment but it is common practice for those on Interferon/Ribavirin to go 48 weeks ($120,000 for dual therapy)

 

These are all rounded numbers and this does not include anything but the drug.  Side effects are horrible.  A few are nausea/vomiting/diarrhea/depression/suicidal and homicidal thoughts/hair loss/anemia/insomnia . The new drugs add full body rash, rectal itching and/or rectal bleeding.  (This reminds me of the old treatments for syphilis: mercury and arsenic).   Many patients cannot hang and drop out. Jobs are lost, families strained and the patients overwhelmed. And then there is that pesky liver transplant for those beyond pharmacologic help (drugs).

But there are currently over 4 million people infected in the US and the largest group are over 50 with long-term damage.  And there are new tests and treatments.  For instance, researchers recently identified a specific DNA sequence in the gene that codes an immune response regulator, called IL28b. Different IL28b sequences predict whether treatment will successfully clear the virus.

With that in mind Goldhaber-Fiebert and Liu of Stanford created a computer model looking for the line at where it makes sense to go through treatment.  Remember that these people think in terms of how many patients out of 1,00 people, not what YOU should do.

After intense statistical and simulation analysis, the model showed that the new triple therapies were indeed cost-effective for chronic hepatitis C patients with advanced liver disease. Despite the large price tag and side effects, the new treatments help these patients avoid costly cancers and liver transplants — as well as allowing them to live longer, higher-quality lives.

For those patients with mild disease, the model indicated that determining their IL-28B genotype is the best next step, before prescribing a treatment.  The closer the threat of severe disease, the more justified treatment costs and risks become, said Goldhaber-Fiebert. “That would be the bottom line.”

Though these new drugs may offer relatively desirable options now, both Goldhaber-Fiebert and Liu noted that additional, and perhaps more effective, drugs are already in clinical trials.”

So in the “State-The-Obvious” department  they conclude: “As more and better treatments become available, the decision will continue to evolve, requiring further analysis, patients and health systems could also benefit from price competition with multiple treatment options available. But ultimately, treatment decisions will remain a private conversation between a doctor and a patient. “

A bit chicken shit but common in the academic world.  All studies end in “Further research is needed”.  Which is academic speak for “See you at the next medical conference where I will have more data”.  Note the reference to “health systems”.  This includes the insurance company.

Now, as a taxpayer, I wonder where the money is coming from. You can see one reason a clinical trial is an attractive option.  I didn’t pay a nickel.  In fact they paid my gas and parking.  BTW my results from 12 week post treatment just came back “No detectable virus”.  So why do I have a trace of cynicism about drug companies pushing for testing?

My mom used to yell, “close the screen door, you are letting the flies out”.  I always thought that was funny. Regarding screening and insurance that may be true but not so funny.

http://www.nlm.nih.gov/medlineplus/news/fullstory_125350.html

http://health.yahoo.net/news/s/nm/all-baby-boomers-should-get-tested-for-hepatitis-c-cdc

http://med.stanford.edu/ism/2012/february/hepatitis.html

Ungrateful Bastard that I am…Hepatitis C

You Bastard, you killed Kenny

Hepatitis C treatment ended five weeks ago.  All is going well (~ nothing is wrong).  Went to Costa Rica with grand kids, hiked (slowly) up mountain sides.  Thank you Symbicort and red blood cells.  Now home.  I want to lay in guest bedroom (my sick room), watch recorded TV shows and eat sugar.  What’s up with that?  Fighting some mental and physical depression.  Back up.  Not necessarily so…anytime things are caddy wampass I frighten myself with the depression (DEBression) stick.  Kinda like a boogie man under the bed.

Ungrateful bastard that I am, I want to just “be okay”.  WTF does that mean?  Everyone who is “okay” raise your something.  Last time I re-uped for life post-treatment, I slowly weeded the front garden to demonstrate focus and progress to myself.  It took a week.  Currently it is 108 F heat index…so the hell with that.  I go to bed and get up the same time everyday.  Learning how to fall asleep naturally.  Not true…trying to learn how to fall asleep.  I’ve always had some distressing insomnia.  Maybe that contributed to my drinking a quarter century ago.  Maybe not. Currently I’m on two non sedating antidepressants and one sedating, slowly weaning off.  I can hear AA people judging.  Ta hell with ’em. Note to self:   What other people think of me is of no consequence.

You’d think I’d be more sensitive to the term bastard.  I’m not.  One thing I’m clear about, being born out-of-wedlock is not my burden.  Not sure I knew that 30-40 years ago.  And views change.

“Now more than half of all births to American women under 30 are born out of wedlock, and the trend in marriage-less birth is becoming an accepted reality of American life.” Don’t you love marriage-less over out of wedlock?  I wonder which group with an axe to grind is funding this.

“According to an analysis of government data, conducted by the research group Child Trends and reported by The New York Times, the last 20 years have seen illegitimacy among white women in their 20s with some college — but not a full four-year degree — rise more quickly than in other groups.”  …gotta love the internet.

Ah, yet another chapter in “Me-Me-Me”  My favorite subject, I am afraid.  Better keep dancing with the psychiatrist a bit longer. 

http://www.mysymbicort.com/

“You bastard, you killed Kenny”http://www.youtube.com/watch?feature=player_detailpage&v=1A6f3jHTC-Y

http://articles.businessinsider.com/2012-02-21/home/31081751_1_illegitimacy-black-children-unmarried-women

Adverse Events in Treatment: If it’s you, it’s minor. If it’s me, it’s major

Adverse Events and Reactions

There are conflicting definitions here because there are conflicting definitions in science and medicine.

A Side Effect (SE) is when a drug does something besides what you are treating. Rogaine was initially a drug for hypertension that had a side effect (SE) causing hair to grow on your head.  It was predictable.  Talk about a marketing turn-around. That  pharmaceutical guy is probably still hailed as a hero. What? Me judge? 

Minoxidil is an antihypertensive vasodilator medication which also slows or stops hair loss and promotes hair regrowth.

Ooh ah, chemistry structure. 

Why is it that I can understand how this crosses the epidermis but I cannot understand how house plans will look as a house?

An Adverse Drug Event (ADE) is something that is dose independent and causes harm.  Wow, the definitions are wide open.

I went to the Veterans Administration (VA) website:   No clear definition  from their panel of experts

I went to the NIH:  The National Institutes of Health (NIH) Blah Blah Blah ”  WTF? I stopped there.  These people had no intention of helping me get  a clear definition. 

 Wikipedia, that bastion of scientific rigor says:

http://en.wikipedia.org/wiki/Adverse_drug_reactions

An adverse drug reaction (abbreviated ADR) is an expression that describes harm associated with the use of given medications at a normal dosage during normal use. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs. The meaning of this expression differs from the meaning of “side effect“, as this last expression might also imply that the effects can be beneficial.[1] The study of ADRs is the concern of the field known as pharmacovigilanceNo shit.  Just what we need, splitting more ill-defined hairs.

An adverse drug event (abbreviated ADE) refers to any injury caused by the drug (at normal dosage and/or due to overdose) and any harm associated with the use of drug (e.g. discontinuation of drug therapy).[2] ADRs are a special type of ADEs.

  • Type A: Augmented pharmacologic effects – dose dependent and predictable
    • Intolerance: Severe decrease in red blood cells (RBCs) with ribavirin.  Decrease dose of ribavirin.
    • Side Effects. Immobilizing depression .  Anti-depression agents can help.

     My question to you and your doctor is “Why not start antidepressants in advance of hepatitis C therapy?”  I did the 2nd time around and I wasn’t on another planet every day.  Only sometimes.

  • Type B: Bizarre effects (or idiosyncratic) – dose independent and unpredictable.

Congratulations!  You are 1 in 100,000 whose teeth fall out.  It is a rare occurrence, 1 in 100,000.  But if you are the one, it is 1 in 1 (100%).  I apologize, I do not remember where I got this mask rendering.  Please don’t sue me.

  • Type C: Chronic effects: You keep taking that boy ,and you will go blind.
  • Type D: Delayed effects:  We didn’t realize that three weeks into treatment your butt hole would fail to shut.  Awkward!
  • Type E: End-of-treatment effects: Seriously, , Ribavirin stays in red blood cells (RBCs) for 6 months after treatment causing teratogenic effects (birth defects)  in non mammals.  Even if only the sire is taking the drug.
  • Type F: Failure of therapy The operation was a success but the patient died.
  • Type G: Genetic reactions OOPs,  you went deaf because you don’t have the enzyme to pee out that drug. Are your parents from Lapland?

My two favorite terms are Bizarre and Idiosyncratic. Bizarre we recognize. Sort of. Idiosyncratic means we have no effing clue. Idiosyncratic is more palatable than ” no effing clue”. 

The Food and Drug Administration (FDA to their friends) says An ADR should not be labeled as ‘certain’ unless the ADR abates with a challenge-dechallenge-rechallenge protocol (stopping and starting the drug). Now, I don’t know about you, but I am probably not going to volunteer to restart a drug that I had to stop because of  a bad experience.  At least not any more.

Both Interferon and Ribavirin warn about severe depression, suicide, homicide, and  crazy thinking.  I got the D and CT.  These are predictable SEs

  From the Interferon (Pegasys) package Insert

http://www.accessdata.fda.gov/drugsatfda_docs/label/2002/pegihof101602LB.htm#cont

BOXED WARNING 

 Alpha interferons, including PEGASYS, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Patients with persistently severe or worsening signs or symptoms of these conditions should be withdrawn from therapy. In many, but not all cases, these disorders resolve after stopping PEGASYS therapy (see WARNINGS and ADVERSE REACTIONS).

Neuropsychiatric

Life-threatening neuropsychiatric reactions may manifest in patients receiving therapy with PEGASYS. Depression, suicidal ideation, and suicidal attempt may occur in patients with and without previous psychiatric illness.

PEGASYS should be used with extreme caution in patients who report a history of depression. Neuropsychiatric adverse events observed with alpha interferon treatment include relapse of drug addiction, drug overdose, aggressive behavior, psychoses, hallucinations, bipolar disorders and mania.   Almost all patients with hepatitis c have a history of depression.  It goes with the territory. 

ADVERSE REACTIONS

Nearly all patients in clinical trials experienced one or more adverse events. The most commonly reported adverse reactions were psychiatric reactions, including depression, irritability, anxiety, and flu-like symptoms such as fatigue, pyrexia, myalgia, headache and rigors. The most common reason for dose modification or withdrawal from studies was hematologic abnormalities.

Ribavirin  http://en.wikipedia.org/wiki/Ribavirin  It is more difficult to get a straight package insert regarding Ribavirin as there are multiple manufacturers.  Of note, Ribavirin has shown teratogenicity in non mammals.  You will have to sign many forms to document that you grasp this.

 I am not the suicide type.  As a kid, I stumbled on my mom trying to kill herself.  Pills, cut wrists, head in gaseous oven.  I would call an ambulance then my Aunt Sudie.   Aunt Sudie kept  my brother and me during hospital stays.  I packed our school stuff in a  cardboard box and waited for her.  We stayed there till Mom promised the psych doctors that she’s better and wouldn’t try suicide again.  Back then you would whisper “She’s had a nervous breakdown”.  You don’t hear that anymore.

It was weird at Aunt Sudie’s house.  It was quiet , clean and ran on a schedule.  They had ice cream all the time  and a freezer that kept it frozen.   My cousins  Gary and Randy would have to room together so my brother  and I could have a bed.  I put every effort into making sure Tim and I were no trouble. Little Orphan Annie has come to our house to stay.  To wash the cups and saucers up and brush the crumbs away…  J W Riley.  This thinking came from me.  Aunt Sudie didn’t expect me to work for my keep.

 When my period  started, Randy’s dog , Lady, shredded my Kotex all over the dining room floor and they saw it.   I died quietly.  At home no one shredded my Kotex stuff.   No matter how bad it is at home, there are some plusses.

Back then there was no Valium or Prozac.  Only Thorazine.  Which Mom used to for suicide attempts. See a pattern?    Mom later found an alternative.  She began drinking with my dad.  I became grown up on duty (GOD) when I was about eleven.

Liver and Onions

My favorite joke:Two cannibals are eating a clown.  One pauses and says “Does this taste funny to you?”     I think this is hilarious!

You know when your liver is being treated, it seems almost cannibalistic to cook  and eat someone else’s liver.  Fellow livers and all.

When I was in treatment for Hep C, My Red Blood Cells (RBCs) and hemoglobin  (HgB) were low.  My friend Trish came from the bay area armed with her Cooking for Cancer Patients cookbook.   She wanted me to eat  chicken liver.  She promised that it wouldn’t taste like liver.   She covered it in curry and stuff.  The flavor wasn’t as horrible as regular liver, but the look and texture felt like a soap dried loofah in my mouth.   Deb, don’t gag.  Eat one and push the others around your plate.  Tried and true techniques.  I did eat three.   I think she left the recipe. The curry rice was good.

When I was a kid, we only had one ghost story.  The whole story was built around “I’m on the first step, I want your liver.  I’m on the second step, I want your liver.  I’m on the third step”…Then you grab kids and scare the shit out of them.  It worked on me every time.  This Halloween classic went along with the dark spook house where you always touched beef liver and screamed.  Those days of course I went home to a big skillet of cows liver, onions and gravy and ate it up.  Or on Sunday, Mom fried a chicken.  The liver and gizzard finished before the rest of the chicken.    I hung around like a little bird.  Mom blew on them and popped them in my mouth.  That was before I had anatomy and physiology.  I still don’t want to think about a gizzard’s function.

Anyway, as soon as I stopped taking Ribavirin, my blood cells began reproducing.  I feel more energy  every day and it is awesome. I will pass on the liver.

Partial Responders with Hepatitis C

All Hepatitis C studies are not created equal. Duh

I used to see myself as smarter than the average bear.  Not so much now.

Being me, I was not passive when searching for a Hep C study.  But I was mistaken.   I assumed. Don’t make an assumption.  I knew better.   My mom taught me this.  Every time some of us kids got in trouble, she pulled me aside and said, “You know better”.  It was years before it dawned on me that other kids knew better too.  My mom was once a kid.  In fact she was still a kid when she had me.  In 1951 it was not cool to have a baby out-of-wedlock.  My biological father passed on marriage and she had to go back home to Harlan County, Ky.   This is where I was born.  Papaw told me to say I was from “Bloody Harlan” because of the bloody mine strikes.   So that is what I told my teacher.  Papaw and all Moms’ brothers were coal miners.  We didn’t make moonshine (the other career path)

I learned that the TV show Justified   is about Harlan County.  I don’t watch it myself.  Makes me jumpy.

fig 1.Me, Mom in the white car coat, dad that raised me, Mamaw, Papaw, and aunts. Harlan County, KY. My mom has the big nose like Papaw.  She waited to get a nose job after Papaw died

Coal tipple loads rail road cars 1

When I was a curly headed baby
My daddy sat me down upon his knee
He said, “Boy, you go to school and learn your letters
Don’t you be a dirty miner like me”

I used to think my daddy was a black man
With script enough to buy the company store
Now he goes downtown with empty pockets
And his face is white as a February snow

I was born and raised in the mouth of the Hazard Hollow
Coal cars rambled past my door
Now they’re standin’ in a rusty row all empty
And the L & N
Don’t stop here anymore

http://www.sing365.com/music/lyric.nsf/The-L-amp-N-Don’t-Stop-Here-Anymore-lyrics-Johnny-Cash/6B378501111ECA5D48256DEA000A5308

I love this song but never heard it until I moved to Texas

Where was I?    Okay brain get back on track.  Let me recommend that you do not have your driver’s license photo taken while on treatment. Very scary.

I chose to participate in a Multi Centered, Randomized, Placebo Controlled, Double Blinded study, evaluating Standard of Care (SOC) Interferon and Ribavirin (which had been my only choice all these years) vs. SOC and telaprevir for round one.  In fact I sought out this study. There were three arms, two with study drug.  I had a 66.7% chance of receiving study drug.  As I learned later, I was not randomized to study drug (telaprevir).  I assumed SOC included addressing anemia and other life threatening events.  In this case, SOC did not include blood transfusions or red blood cell (RBC) stimulant injections such as Procrit.  Standards of care have not caught up to current practices. Step one was to reduce the Ribavirin dose.  .  My hemoglobin (HgB) was 8.9 and the guideline minimum for taking Ribavirin is 10.0. Normal HgB range for females is 11.5-15.8 mg/dL.   My Ribavirin dose was decreased. Hemoglobin got slightly better but I paid for it later by not clearing the virus. In order to treat the anemia I would have to walk away from the study.  Dang it!   I quickly lost the ability to walk down a hallway, climb stairs or lift baggage without major shortness of breath (SOB) and the ability to complete a thought, all necessary for my job (oops, career). More about that later.

After treatment completion, an individual is assessed for response to measure viral load. If there is virus remaining but a reduction of disease by 30% or more  – it is called a partial response.   Partial response (PR) implies further treatment  required.  www.about.com   I moved from treatment naïve to partial responder.  Here I had saved myself for newer treatments but still got the same treatment that was available years ago.  Plus no treatment for the anemia.  How did a smart girl like me get in a dumb box like this?  I hung in there and finished the (long) 48 week trial.  Not only did I not have red blood cells (RBCs) or white blood cells (WBCs), but then the virus that was left was a stronger warrior.   Not good.  Here is the part where my education went out the window.  I was so depressed that I couldn’t function.  Every little thing was monumental.  I should have quit the study when my blood chemistry went to hell.  But I couldn’t think clearly enough to look at the situation logically.  All my decisions were made by a scared little girl.  See fig 1

You know I wanted to blame insurance companies.  It is so easy to blame insurance companies.  I wanted to blame pharmaceutical companies and the FDA.  They are easy targets too.  In reality, I, more than most, understand the study requirements and commitments. Sort of. I have been a research pharmacist for a couple of decades.  The data must be unsullied from outside forces like blood transfusions that will make it impossible to evaluate the toxicity.  That is the point of the study, not patient care.  Don’t misunderstand me.  Patients are well cared for. A patient can get treated without a study but a study cannot evaluate a treatment without patients

FYI, HgB is the molecule in the blood that carries oxygen, (O2) from your lungs to your blood and carbon dioxide (CO2) to your lungs so you can exhale this gas.  Speaking of HgB, it is a bucket brigade that carries water to a fire.  Even if you have plenty of water, if you don’t have enough buckets, the barn burns down.  Wait, that wasn’t a great example.  It wasn’t completely accurate either.  Never mind.  It’s just that I spent all these years learning this stuff; I want to get my money’s worth.  Kurt Vonnegut said only hermaphrodites use a semi colon; .Sort of.  While metaphorically I don’t relate to that, he did say it.   I didn’t pay Kurt Vonnegut, God rest your soul Mr. Rosewater.  Anyway my WORD grammar check said uses it.  I think I paid for that.  Yes of course I did.

Telaprevir (Incivek) and boceprevir (Victrelis) are now available to add to Standard of Care (SOC).  In fact by now they may be a part of SOC.  Glad I contributed to the body of knowledge that is clinical research.  Really I am.  But I wouldn’t repeat round one for nothing, not no way, not no how. It was two years before I was well enough to go for round two of treatment.  My career never recovered.