Fibrosis Testing; New Options On The Way

There is a lot of jargon in here, hang with me.

Now about Cirrhosis: You have Hepatitis C and your doctor wants to check your liver for damage

The gold standard for diagnosis is a liver biopsy. This procedure takes place in the hospital. While you are under a local anesthetic, a physician uses a needle with grabbers to remove a tiny sample from your liver. Once the biopsy is completed the patient must lay flat for 6-8 hours to confirm a lack of bleeding, then go home and do nothing strenuous for days.

The sample is studied by a pathologist to assess liver scarring (fibrosis). While liver biopsies are invasive and do have inherent dangers (excessive bleeding, infection, hypotension), they also have variable results, depending on who is reading the results. It is better to have two pathologists study the specimen but this isn’t always practical.

There are promising alternative tests. New tests can assess the severity of the fibrosis in individuals at high risk of developing liver cirrhosis (e.g., chronic alcoholism, chronic viral hepatitis). These tests include breath testing, blood tests, and imaging techniques.

  • Ultrasound initially showed 94% accuracy, but that score has been downgraded. But in the US it is cheap and widely available
  • Ultrasound with contrast media is about 79% accurate but contrast media is expensive and not always used in compromised livers
  • Doppler checks the blood flow through the hepatic vein. This shows overlap of staging cirrhosis and therefore not a good choice
  • CT Scans look at the whole abdomen so subtleties can be missed
  • MRI has an accuracy of 80-89% but requires a high level of technique which is not always available clinically and is expensive
  • Biomarkers can establish cirrhosis and non-cirrhosis but not grades of scarring
  • Biomarkers: Indirect
    • Fibrotest is useful in diagnosing and grading fibrosis. This test has established measurements and may be used in place of a liver biopsy for patients with Hepatitis C
    • FIB4 uses a panel of biomarkers and can also be used instead of liver biopsy.
  • Biomarkers: Direct
    • HA (hyaluronic acid) normally occurs outside the circulatory system but can be evaluated by update in scarred vs normal livers. Scarred livers leave more HA behind while normal livers convert more to remove it from the blood.
    • PIIINP and PIINP
    • TIMP-1
    • YKL-40

All the tests listed above have varying degrees of accuracy but liver biopsy is still the standard for staging of scaring (fibrosis).1

Symptoms

The early stages of cirrhosis often produce no symptoms. As scar tissue replaces healthy cells, the liver begins to fail, and symptoms may become evident. The severity of symptoms depends on the extent of liver damage.

Because the liver is crucial for many metabolic activities, cirrhosis impacts a wide range of the body’s functions, including nutrient and hormone metabolism, blood clotting, and processing of ammonia and other toxic wastes. Many of the symptoms of cirrhosis are directly related to disruption of these functions. However, most of these symptoms can also be caused by other conditions, so it is important to consult with your doctor if you experience any of these symptoms, particularly if you have risk factors that increase your likelihood of developing cirrhosis.

Early symptoms of cirrhosis include:

  • Fatigue and weakness (related to anemia and altered nutrient metabolism)
  • Poor appetite
  • Depression
  • Nausea
  • Weight loss
  • In men: A decrease in liver metabolism can contribute to: Impotence; Reduced testicle size; Enlarged, tender breasts; and/or Loss of interest in sex—due to altered liver metabolism of sex hormones
  • Small, red spider-like blood vessels under the skin—caused by increased pressure in the tiny blood vessels due to liver congestion
  • Increased sensitivity to drugs—due to reduced ability of the liver to inactivate them

Symptoms become more pronounced as cirrhosis progresses. Later symptoms, some of which are due to complications, include:

  • Reddened or blotchy palms
  • Sleep disturbances
  • Ulcers
  • Fever and other signs of infection—due to altered immune function
  • Peripheral neuropathy
  • Frequent nosebleeds, skin bruising, or bleeding gums—resulting from decreased liver synthesis of clotting factors
  • Ascites —water retention and swelling abdomen caused by obstructed blood flow through the liver and reduced synthesis of the protein albumin
  • Bacterial peritonitis—infection of ascites causing abdominal pain and fever
  • Itching—caused by deposition of bile products in the skin
  • Jaundice —yellowing of the skin or eyes due to build-up of bile pigments (bilirubin)
  • Vomiting blood—due to swollen veins in the esophagus that burst
  • Encephalopathy and coma—mental changes, including forgetfulness, trouble concentrating, confusion, and agitation, caused by the build-up of ammonia in the blood
  • Decreased urine output and dark urine—caused by kidney dysfunction or failure
  • Liver cancer

This is an extensive list of symptoms but not complete. Each person is different. Remember that by taking care of your liver, some damage is reversible.2,3

  1. World Journal of Gastroenterol. 2014 Dec 7: 20 (45).
  2. American Liver Foundation.
  3. National Library of Medicine.

For You New Guys: Now What?

I wrote this article for www.hepatitiscnews.com.  Visit their site for more information.

You have hepatitis C (HCV) and have only heard scary things. Your best friend is knowledge, not just facts. It is no good to just bring your liver to treatment. You must bring your mind as well.

Quit drinking or taking drugs? If not, come back when you do.

What to learn:

Doctors: Your insurance will pay the same amount for a hepatologist or a gastroenterologist. Go for a hepatologist. All he thinks about is the liver.

Treatment Lingo: Learn it. This language is the only way you have to talk with your treatment team.

  • VR: Viral load – number of viruses per ml of blood is written      in logs
  • Log: simply a way to not write all the zeros in a number. 1,000,000 is 1 million viruses per ml of blood, is 6 logs
  • RVR: Rapid Virologic Response – hep C undetectable at week 4 of  treatment
  • NR: Null Response – no decrease in virus at week 12 of treatment
  • PR: Partial Response – small decline in virus at week 12 but still detectable at week 24
  • SVR: Sustained Virologic Response – undetectable virus 6 months after treatment completed. The goal!
  • Genotype: Most people in the US are Genotype I. Learn yours. Treatment choices are based on genotype

Depression: If you are like me and inclined toward depression, ask your doctor if you can start antidepressants before treatment. It’s easier to get ahead of depression than try to catch up to it. This can make the difference between completing treatment and not.

Available Treatments: Currently the standard of care (SOC) includes Interferon, which is harsh. Soon treatments will be available without Interferon. Can you wait? Talk to your doctor. All treatments include at least 2 drugs to attack the virus at two different sites in the life cycle (think of killing fleas on your pet).

flea life cycle

Another approach: I am a scientist as well as a treatment success. Here is what I did and why: I looked up clinical trials in my city at clinicaltrials.gov. I found a research site and participated in trials there.

The advantage: Newest treatments and a team focused on my health with close monitoring of my whole body, not just my liver. All treatment is free and you can opt out if you don’t feel comfortable.

The disadvantage: You must commit to follow the protocol. My first treatment drugs were SOC and didn’t work so I went through treatment again. But, this was successful and I am cured!

One note of warning: They are researchers and so they don’t know all the answers to treatment outcomes. Phase III means that many patients have experienced this drug and more is known about safety. Phase II means the drug has only been in a few humans, so less is known about safety. I suggest only participating in a Phase III trial if you aren’t comfortable with the unknown.

I wish you the best and suggest taking it one day at a time.

on the farm

on the farm

Things Not To Say to Someone Who Just Completed Hepatitis C Treatment

Now What?

Now What?

  • You were in treatment?  I just thought you were aging badly.
  • Now make sure you don’t get it again (my personal favorite)
  • How do you celebrate without alcohol?
  • How can you be sure you are cured? I’ve heard it comes back.
  • I heard of a guy that went two years then his liver blew up.
  • Some guy finished treatment then killed himself.
  • Can you talk to my husband?  He won’t quit drinking and drugging.
  • I saw a website that says St John’s Wort works better.
  • Want to volunteer at the hospice?
  • Too bad you have to give up your handicap placard.
  • Glad you finished.  Maybe you won’t be such a moody A Hole now.
  • You should have waited for newer treatments.  They are better.
  • Now, shut up about your symptoms.
  • Good, now get off your butt and do something.
  • Now what?

Hepatitis C Treatment Management: What would Mamaw Do? WWMD?

Mamaw and Papaw’s Wedding Day 1916 Livingston KY

The world of Hepatitis C treatment  is more than taking drugs as scheduled and hoping for virus death.  The bigger part is keeping  your body, mind and soul with you.

  • Diarrhea?  Water and Lomotil I guess, that was never my problem
  • Nausea?  Water, saltines and Phenergan
  • Constipation?  Water and stool softener.  Even the name is too gross.  Kinda like mud-butt
  • Mouth Sores?  Water then swish and spit Mylanta.  Happy to spit
  • Food taste like pennies? Water and floss, floss, floss, brush, brush, brush.  Still doesn’t help
  • Flu symptoms for six months?  Water then alternate Tylenol and Advil for six months.  Exercise: yeah, right
  • Rash? Benadryl oral and topical.  Maybe hydrocortisone/vaseline
  • Insomnia?  Ambien if you are lucky.  Benadryl if you are unlucky, it adds to constipation and taste of pennies.  Don’t drink water before bed
  • Depression? Water and SSRIs/SNRIs/antipsychotics/and on-and-on in couplets
  • Too tired to work?   Adderall if  the shaking won’t vibrate your loose screws
  • Can’t go on?  Cry really hard, take Advil, drink water and go on.

My Mamaw had eleven children in Eastern Kentucky  starting in 1917.  There was no doctor, drug store or money.  She lost two baby boys, one to the Spanish Flu.  When she came out of delirium, baby Bentley was already buried.

If an artery spurted, she applied coal soot.  Got a burn?  First well water (cold) then let egg white dry on burn or apply a slice of onion.  Step on a nail?  Clean and soak with turpentine.   Pneumonia?  Inhale kerosene (dosing was tough) through a moist cloth and put a mustard plaster on your chest.  It will kill you or cure you.  I never witnessed this  one.  Croup?  Make a sheet tent over the steam kettle, put in Vick’s and then hold the child under the tent.  If that treatment doesn’t work, sugar with a drop of kerosene. Give a few drops of whiskey if you got it.

a dose of pee

Here’s what applied to us grandkids. Pinworms?  Check rectum at night with a flashlight then give all the kids a stinky medicine that I think had tobacco in it.   Earache?  Warm up pee in a teaspoon a little more than body temp  and pour it in your ear. Stick in a plug of quilting. I would hide in the cedar closet  as long as I could before telling Mamaw.  I made her use my pee.  Here is the thing: it worked. Pee is sterile upon leaving the urinary tract.  Of course I knew nothing of a “clean catch”.  Collection was easier when we got an indoor bathroom.  You figure it out.  When I checked the internet for possible mechanisms of action (MOA) of the pee, there was a claim that urine is an antifungal.  Of course on the internet you can probably find a claim that golf balls extract is good for an earache too.  I made that up.

Mamaw’s rocker and sock monkey

What would Mamaw do about Hepatitis C treatment management?  Probably just rock me and say “Doggone it.  It’ll get better.”    I have her rocker in my house.  It sure is smaller than I remember.  Anyway,  it doesn’t really work without her.

Hepatitis C: Beware the Jabberwok

 Hepatitis C:  Beware the Jabberwok

Through the Looking Glass

‘Twas brillig, and the slithy toves
Did gyre and gimble in the wabe:
All mimsy were the borogoves,
And the mome raths outgrabe.

‘Beware the Jabberwock, my son!
The jaws that bite, the claws that catch!
Beware the Jubjub bird, and shun
The frumious Bandersnatch!’

He took his vorpal sword in hand:
Long time the manxome foe he sought 
So rested he by the Tumtum tree,
And stood a while in thought.

And, as in uffish thought he stood,
The Jabberwock, with eyes of flame,
Came whiffling through the tulgey wood,
And burbled as it came!

One two! One two! And through and through
The vorpal blade went snicker-snack!
He left it dead, and with its head
He went galumphing back.

‘And hast thou slain the Jabberwock?
Come to my arms, my beamish boy!
Oh frabjous day! Callooh! Callay!’
He chortled in his joy.

‘Twas brillig, and the slithy toves
Did gyre and gimble in the wabe:
All mimsy were the borogoves,
And the mome raths outgrabe.    

  

If you listen to a scientific lecture for an hour, you can begin to believe nonsense is science, but don’t.

I believe that the average Hep C patient (whoever that is) has a triple cross to bear.     1. You feel like shit on a stick  2. You have to go to unimaginable places like a liver biopsy suite and 3.You are thrown into a parallel universe where the language is almost understandable, but not really. It’s Jabberwok.

I was listening to a lecture yesterday on Hepatitis A through E. I was reading the slides as Dr. Nice Lady from pharmacy was talking.  And then I heard it:Hepatitis B and C are predominately associated with percutaneous and permucosal transmission”.  Translation:  Hep B and C can be caught through blood and through sexual contact.  Permucosal  is medical lingo for via mucous membranes.  The problem was that fifty pharmacists were about to  leave the lecture and tell their worlds that you can catch Hep C through sex.  I couldn’t let that happen so I said through the chat box “Hep C can be caught through sexual contact?  Is this new information?”  She said no, you are right to point that out, it is not transmitted that way.  So why did she say it?  The slide looked better that way.

In reality, the way one gets Hep C through sex is through rough sex and I mean rough.  Percutaneous means blood transmission.  I will pause here so that you create your own image.

Now I was willing to let it slide when she said that Hepatitis A and E were transmitted through the oral-fecal route.  In reality it is fecal-oral route.  Think about that for a moment.  But my point is that there is a lot of slightly non-true information out there.  What can you do about it?  Ask questions wherever you go.  Even if you have asked the same question before.  Remember how your doctor’s office always has that sign in English and Spanish that says Questions/Pregunta?  They really want you to ask.

Boy, did spellcheck light up Jabberwok!

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

Lewis Carroll Through the Looking Glass

Viral Hepatitis:  Keeping Your Patients Safe www.freece.com

Hepatitis C Now Godzillaprevir and KingKongViracide: Yes but is Interferon Still in the Mix?

GodzillaPrevir

KingkongViracide

No matter how powerful add-on drugs are, if Interferon is still part of the mix, many patients will not be able to finish the treatment.  If I was in early stages of Hepatitis C with minimal liver scarring, I would wait 12-24 months for new treatments sans Interferon.  If my Hepatitis C were more advanced, I would go to www.clinicaltrials.gov and type in my disease and city. (Note disclaimer at end of blog)

Below are “press releases” from companies and are mostly targeted to investors, e.g. The market for treating hepatitis C has burgeoned  (My spellchecker doesn’t recognize this as a word) in the last year.

Always look at the source of medical information, if it is Kiss Your Assets Good-Bye or Liver Heard on the Street, run away. If it is the New England Journal of Medicine, or Gastroenterology proceed with caution and a jaundiced eye.  Oops a hepatitis pun.

Dec 1, 2011 – Novel Hep C Treatment Excludes Peginterferon Alfa By: DENISE NAPOLI, Internal Medicine News Digital Network Therapy with a novel

But then if I didn’t read the business news, I wouldn’t know about this for another couple of days:

Bristol-Myers Drops Hepatitis C Drug After Patient Death

Daniel Acker/Bloomberg

Bristol-Myers Squibb Co. has abandoned an experimental hepatitis C pill it bought for $2.5 billion earlier this year after one patient died and others were hospitalized while taking the drug in a study.

                    

Bristol-Myers will take a charge of $1.8 billion in the third quarter related to research and development of the therapy, the New York-based company said in a regulatory filing today. The drugmaker suspended testing the medicine, known as BMS-986094, on Aug. 1 after a patient developed heart failure.

Bristol-Myers said yesterday it has discontinued development of the drug, part of a class of medicines called nucleotide polymerase inhibitors, and was consulting with U.S. regulators to assess the treatment’s effects. Along with the death, eight patients suffered from heart and kidney toxicity, the company said in a statement.

“Bristol-Myers paid a fortune for a pearl that turns out to be fake,” said Erik Gordon, a University of Michigan businessprofessor who follows the health industry, in an e-mail today, referring to the company’s “string of pearls” name for its acquisition strategy. “The Inhibitex acquisition shows the dangers of paying huge premiums for late-stage drug candidates in hot areas. They still can fail.”

I love it:  The dangers of paying huge premiums…Not the dangers of participating in clinical trials. No disrespect to business people, just a different perspective.  I should know, I worked in Big Pharma for twenty-five years.  First make money for share holders, then do no harm to patients.

dictionary.reference.com/browse/inherent existing in someone or something as a permanent and inseparable element, quality, or attribute:

There is inherent risk for patients in clinical trials.  You can quote me on that.

Hepatitis C Lingo: What is a Log?

Okay, you are going into treatment.  You must understand the language of treatment progress. No one values your health more than you.

Getting information off the Internet is like taking a drink from a fire hydrant.   Mitchell Kapor

 Treatment response is a topic of great importance to me, you, and doctors.  They need  to see if the treatment is working enough to keep poisoning you.

Viral load is how to measure response. It’s done  by looking at the amount of virus in your blood. Viral load is checked before treatment,  at week 4, 12, and either 24 or 48, depending on duration of therapy, then 24 weeks (6 months) after therapy.   The response is measured in log reduction.    In fact log stands for logarithmic.  So what?  Each log corresponds to a factor of 10.  So what?  A 1-log reduction means virus decreases by 10 times; a 2-log = 100, a 3-log = 1,000, a    6-log reduction = 1,000,000 = 1 million.  Log is a way of not writing down all the zeros.  Just count the zeros gone and you get the number of viruses that died per ml of blood and went away.  Sort of.  There, in one paragraph we discussed a concept that took me some time to learn.  And you thought you would never use that math junk.

When I was in middle and high school, I had it in my head that my brain wasn’t “smart enough” for math and chemistry, even though I skipped kindergarten and the 2nd half of my senior year.   So I avoided the hard sciences.  Remember I was still GOD, grown up on duty, at my house. Then in my 20s, I went to college and I decided I didn’t want to fear math and chemistry any more. I took inorganic chemistry with algebra on the side to understand the language of thermodynamics.  This is an example of how my childhood perceptions always played down my abilities even though my family said I was smart (which I loved but didn’t believe) . I graduated from pharmacy school at 30,  then went back for a Dr. of Pharmacy in my 50s (while traveling around the country for work and, unaware that Hep C was dragging me down).

Why am I interjecting these little stories in the middle of scientific drama?  Because there is no scientific drama!

All measures must have units:  pounds of pressure per square inch (PSI), miles per gallon (MPG), ears of corn per stalk (one).  Notice the word per in each. The  Hepatitis C virus (HCV) is number of copies of the virus per ml of blood. The hepatitis C virus, like all viruses, cannot reproduce by itself. It must first infect a living cell, such as the hepatocyte, and take over the cell’s “machinery.” Using the genetic information in your cell, the hepatitis C virus is able to make copies of itself which can go on to make more copies.  The virus is measured in copies per ml of blood.  I know, weird.

Lindenbach B, Rice C (2005). “Unravelling hepatitis C virus replication from genome to function”. Nature 436

BTW, kids in Middle School know this stuff.  Amazing.    We will talk about RNA another time.  I know you can hardly wait.

Source:  Vertex website, Wikipedia

http://www.vrtx.com/assets/pdfs/VRTXHCVTreatmentResponse.pdf

www.wikipedia.com

and my brain: no link