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.

Liver Fibrosis Testing Improvements

Image

Don't forget your lipstick

Don’t forget your lipstick

Cirrhosis is a chronic lesion with the accumulation of scar tissue and that alters the structure and function of the liver. Once a patient is cured of Hepatitis C, the danger is not over if the liver is heavily scarred. Currently there is no cure or reversal agent for cirrhosis short of a transplant.

 

 

As cirrhosis progresses, the liver tries to heal itself but the cycle builds scar tissue upon scar tissue and blood cannot flow through the liver. This causes a backup of blood which causes portal hypertension (high blood pressure of the liver). This is incompatible with life. When the liver cannot filter blood, the body compensates by growing vessels around the liver to move blood. And life threatening consequences occur. Frequent results are the pathological creation of blood vessels, ruptured veins in the stomach and esophagus, the inability to stop bleeding, liver cancer, therefore death.

In the past, treatments have targeted blood vessel growth to prevent new weak blood vessels that burst under pressure.

  • Drugs that stop blood vessel growth, do the same thing in the brain and throughout the body so the blocking of VEGF (vascular endothelial growth factor) receptors is damaging to normal blood vessel growth.
  • Most therapies are delivered by blood, but since the liver is scarred, the drugs bypass the liver and sight of inflammation and scar tissue.

Sounds complicated doesn’t it?  Well if you have received treatment for Hepatitis C, you already have a working knowledge of the liver.

Scientists say as the liver attempts to repair itself, the new nodules have high levels of CPEB4 protein and these new nodules form liver cancer cells. CBEP4 has been linked to blood vessel growth in brain and pancreatic cancers. By blocking CBEP4, normal vascular cells grow but the damaged nodules don’t. These experiments have been performed in cells in vitro, animals, and in sample tissue from patients with cirrhosis.

The researchers are working on the role of blocking proteins, and possible treatments for liver carcinomas. Currently liver carcinomas are the main liver cancer and the third deadliest cancer world-wide, with a 5-year survival rate of less than 10%.

In another study a team at The Salk Institute has identified a molecule, JQ1, which has shown promise in the prevention as well as reversal of liver fibrosis in animals. This molecule interferes with the master regulator of liver fibrosis, BRD4. This treatment is at the gene level, and works to block fibrosis formation for patients with cirrhosis from alcoholism and hepatitis. Currently JQ1 is a prototype of a new class of drugs tested in human clinical trials for various cancers.1,2

 https://heplikeme.wordpress.com/wp-admin/media-upload.php?post_id=1099&type=image&TB_iframe=1

view references

  1. Gastroenterology (2015) doi: 10.1053/j.gastro.2015.11.038
  2. Scientists in Barcelona discover a potential treatment for cirrhosis. Institute for Research in Biomedicine Barcelona. Published December 11, 2015.

This article is also published in https://hepatitisc.net/living/fibrosis-and-cirrhosis-news/  Please visit  Hepatitis C News  for more topics

So Called Hepatitis C Science Panel on Bias

I read the transcript of a panel discussion regarding Hepatitis C and bias.  The facilitator was a Ph.D. who did not share her area of expertise. My bias is showing here.  Is she knowledgeable about Hepatitis C or bias,  or is she a facilitator for hire?  The panel was a registered nurse, a social worker and a patient, all with Hepatitis C.  Sounds promising.

But the summary of the discussion was this:

  • We need more money from the government to educate people with Hepatitis C about treatments.
  • We need more money from the government so we can support Hepatitis C patients in the same way HIV patients have been supported, with more teams (I am not clear as to what this statement means).
  • The patient’s affirmation was “Sticks and stones may break my bones but words will never hurt me” and “I learned a lot from a support group made of fellow Hepatitis C patients”.

I am with the patient, the tools are within as opposed to without. If solutions tie to outside money or the government, no progress is  made  and we are stuck. But if a new patient begins his journey with only a support group and he feels like shit (which he will), the danger of isolation is there and almost guaranteed.  I suggest adding a couple of strong friends or family members who can take turns helping you ride this bull, to keep you on for the eight seconds  (treatment duration). Forgive my analogy, I am from Texas where that makes sense. Two wonderful people for me were my husband and  the nurse. But, each patient experience is unique.  Keep trying until you find who and what helps you the most.

The pharmaceutical companies are reaching out to the masses.  They are talking about testing new treatments.  The companies are portraying patients as members of society, people who the general population can relate to. Not just the parrot heads and junkies as portrayed in the past.

parrothead BTW, I overheard my first hepatologist refer to Hep C patients in the waiting room as parrot heads (followers of Jimmy Buffett). That was my introduction to the label. I shared my thoughts with him about that descriptor for patients.

The pharmaceutical company  groundswell will reduce the stigma of having Hepatitis C.  Sure the motive is profit. So who cares?  Not a cured person like me (cured makes me sound like a ham). I worked in the pharmaceutical world for a quarter of a century. Research departments, when not linked to marketing, do great work. That is all I need to know. Let the insurance companies fight out the money issues. Give the insurance companies something to focus on other than patients. Oops, my damn bias is showing. I am curious to see how the “Affordable Care Act” (Obama Care) approaches  Hepatitis C.

As the panel patient points out, it is my efforts that will provide my shield from stereotypes. At least until the drug company marketing departments get the job done.

check out http://www.hepatitiscnews.com where I, and other people with Hepatitis C, share information.

Hepatitis C: The Post Interferon World has Five Scoops of Good News

Hep C:  The Post Interferon World is Five Scoops of Good News

  1.  Increased number of patients screened and identified
  2.  Increased options for those who failed previous therapies
  3.  Improved patient compliance
  4.  Possibilities of patient-guided treatment
  5.  Decreased need for liver transplantation
Donna Reed on Laundry day.  Now her modern day peers can get tested.

Donna Reed on Laundry day. Now her modern day peers can get tested.

  •   I quit writing my blog when I saw the first ad for Hepatitis C treatment on television. The representative people were not parrot heads or crack heads. They were typical ad people like Crestor or Nexium. These ads will bring people in for testing and treatment.  The early treatment decreases transplantation demands. But there is still a lot of Hepatitis C news, so I am back.

A friend of mine started round four of treatment three days ago and she is scared.  Because of Interferon and depression, she could not complete previous treatments. No pledge from me or her physician made a dent in her fear but time will show her. Her new protocol doesn’t call for Interferon, and she is on preventive anti-depression medication. The three drug cocktail for her is one of many not available six months ago, a bygone era.

I recall Fridays during treatment, Interferon injection days. Bathing and grooming started on Wednesdays. I could schedule most work meetings (via telephone) for Thursday and Friday. There is much compliance built around Interferon day. For me, there came the day I could not  work and Friday no longer mattered. Unfortunately leaving work isn’t always an available solution. I lost my career when I returned and I was still sick from drugs. Luckily I retired with benefits.  When I went through treatment # 2, I wasn’t working and could get all the rest required. In the post Interferon world of (mostly) no Interferon and ribavirin this may not be an issue, thus better patient compliance, and cure.

 

And now about patient-guided therapy and no you do not get to select from a menu. For those of you following genotyping using IL2b.  Researchers predict (I love that phrase) which treatments will work best in your body.  That will partially determine the treatment drugs for you, thus ruling out waste-of-time and money treatments.

Be sure to visit my friends at http://www.hepatitiscnews.com  They have great usable info and practical application.  They carry my blog too.

https://us-mg4.mail.yahoo.com/neo/launch?.rand=084ro4ia0h0pr#1

Kentaro Matsuura, Tsunamasa Watanabe, Yasuhito Tanaka

Disclosures

J Gastroenterol Hepatol. 2014;29(2):241-249. 

Hep C Treatment: Do We Or Don’t We? And Who the Hell Does Egypt Know That We Don’t?

I’m going to  ask you to hang with me on this one.  It is a lesson in pharmaceutical pricing and what your insurance will/can pay. Medicaid can’t! 

I worked in Big Pharma Research and Medical Affairs for a quarter century.  So? I see pricing strategies for Hepatitis C treatment compounds and they will affect you.  Let’s look at:

  1. Pricing Strategies for Big Pharma, and they DO have one for who, how much, and how long
  2. How some get to bypass this pricing strategy entirely
  3. Why patients will unnecessarily suffer with this curable Hep C

These days you can’t swing a cat without uncovering a new treatment on the horizon!  Good! Right?  Mostly.  Big Pharma competitors have a short time on top and intend to make  as much profit for stakeholders (stock holders)as possible.  It is the job.

Remember when Vertex launched Incivek (telaprevir) fourteen months ago?  First new drug in forever.  All new patients were given Incivek along with the standard cocktail of Interferon/Ribavirin.  Vertex was the new darling in hepatology, for a year. Sales went from $76.1 Million Q 1 2013 to $44.3 Million Q 4 2013. Now they have dropped out of Hep C research because there is a new rock star launch; Gilead Sciences with Sovaldi (sofusbuvir).

“Record sales of a new hepatitis C drug, Sovaldi, pushed the first-quarter earnings of Gilead Sciences far beyond expectations, the company reported on Tuesday, Sovaldi (sofusbuvir), the company’s $1,000-a-pill medicine to treat hepatitis C, had sales of $2.27 billion in the first quarter, the company said in a statement. That beat an average of analyst estimates by more than $1 billion. The Foster City, California-based company also reported profit excluding certain items of $1.48 a share, beating by 56 cents the analysts’ average estimate (GILD:US). (Yes that is Billion not Million.) The hepatitis C sales are “above even the high end of buy-side expectations,” Mark Schoenebaum, an analyst with ISI Group LLC in New York, said in a note to clients. He called it the best drug introduction in history. Gilead, the world’s biggest makers of HIV drugs, yesterday reported total first-quarter revenue of $5 billion.

Gilead is awaiting U.S. regulatory approval of a two-drug combination with Sovaldi that does away with shots that boost the immune system, yet produce side effects. Company executives said they are aware of the price criticism and the sustainability of spending on the drug. “There are natural limits on what I think is appropriate for next generation products,” Chief Operating Officer John Milligan said yesterday on a conference call.”

 

“If cost were not a factor, we would want to treat the entire population,” said Dr. Rena Fox, a professor of medicine at the University of California, San Francisco. She said it was frustrating that “we finally get this great treatment and then we withhold it.” 

Ah,  my point exactly.

And then there is Egypt. Yes that Egypt.

On March 12 the Egyptians declared  that negotiations between the ministry and the American company were successful and Egypt will obtain the drug for only 1 percent of its price internationally, according to Al-Masry Al-Youm. Adawy, Minister.  The price of a one-month prescription in Egypt will cost $300 while in the U.S. it costs $28,000 a month. (Yes that is Hundred, not Thousand).  The full course will cost $13,000 instead of the $168,000 it costs in the U.S.. They agreed to support making hepatitis c a top priority and to intensify efforts to provide the required medicine at “affordable prices”. According to Reuters, Gilead said on March 22 that it was “pleased to have finalized an agreement” to provide the cure to Egypt, one of the countries with the highest rate of hepatitis C patients.

 

 

May 6, 2014:  Janssen Submits Supplemental New Drug Application to U.S. FDA for OLYSIO™ (Simeprevir) for Once-Daily Use in Combination with Sofosbuvir for 12 Weeks for the Treatment of Adult Patients with Genotype 1 Chronic Hepatitis C. AbbVie, Merck, Bristol-Meyers-Squibb and Johnson & Johnson have potential treatments on the horizon. This is why Gilead is gouging now.  Big Pharma calls it recouping research money. Some is profit too.   It’s all perspective.  Which a Hep C patient is sorely missing.

I shit you not. Thanks for hanging with me on Big Pharma Pricing.  Now you can teach MBA students.  I am feeling powerless though.  Maybe you know someone in Egypt.

One last thought:  I am clear of Hep C Virus after two years and I wish this for you.

Go see my friends at http://www.hepatitiscnews.com  They have great helpful news all the time!

hcvnewdrugs@gmail.com

 

http://www.businessweek.com/news/2014-04-22/gilead-beats-hepatitis-c-sales-estimates-by-1-billion

 

http://www.fiercepharma.com/story/vertex-profits-one-time-gain-despite-plummeting-incivek-sales/2014-01-29

 

 

 

 

 

 

 

 

The Depression Road Goes On Forever and The Party Never Ends *

Hepatitis C and Depression: I should be weary of this subject, but I’m only weary of depression. Thirteen months ago I completed a clinical trial for Hepatitis C. I was cured, c-u-r-e-d.

 GS-US-256-0124-A Phase 2B, Trial Evaluating Using Combinations of Oral Antivirals (GS-5885, GS-9451), PegInterferon Α and Ribavirin In Treatment Experienced Subjects  With Chronic Genotype 1 Hepatitis C Virus Infection

Last month I went in for my one-year follow-up visit where it was confirmed “No Virus After One Year!”.  Okay, maybe it’s true.  Maybe. I answered questions about my mental well-being.  I felt great and said so.  Later I remembered that I felt great because I was on two anti-depressant drugs, Lexapro (escitalopram)  and Wellbutrin (bupropion XL) with a splash of trazodone at bedtime.

BTW, I think everyone should speak about their antidepressants. I know there’s a bunch of us out there.  Just look at the sales $$$.     I worked for Lilly when they launched Prozac.  Rather than get it for free, I paid at the retail pharmacy because I didn’t want anyone to know.  That’s Bull Corn.  Bull Corn?  Where did that come from?

Where was I?  So two weeks ago, my psychiatrist,  (who treats Hep C patients) began to decrease the Lexapro with the goal of decreasing my antidepressant load.  My scaffolding crumbled under me and I spiraled into an anxiety-ridden, weeping insomniac in just a few days and nights.

I've come undone
I’ve come undone

.So,  I am miserable and looking at increasing drugs.  My first thought was that I am FUBAR (Fucked Up Beyond All Reason/Recognition/Repair  military slang) and that’s that.  My second thought was to work closely with Dr _ who assures me that this is a minor setback. Minor to someone else maybe. How quickly I become self-absorbed.

Now, after 400 words, the reason for this blog.  Today I received this article from  Medscape.

 Psychiatric Treatment Considerations With Direct Acting Antivirals in Hepatitis C   Sanjeev Sockalingam, Alice Tseng, Pierre Giguere, David Wong
BMC Gastroenterol. 2013;13(86)

(Newly published articles in my areas of interest for August 9, 2013: Medscape)

Can’t resist the title can you?  I know I can’t.

Being a Doctor of Pharmacy and a scientist, I love articles like this. It takes my entire nineteen years of schooling to follow the data dump. Gastroenterologists and Psychiatrists won’t read this article. It falls into a discrete category that gets filtered out during literature searches. DAAs means previrs ( boceprevir / telaprevir).

Abstract

Background Despite recent advances in hepatitis C (HCV) treatment, specifically the addition of direct acting antivirals (DAAs), pegylated interferon-alpha remains the backbone of HCV therapy. Therefore, the impact of DAAs on the management of co-morbid psychiatric illness and neuropsychiatric sequelae remains an ongoing concern during HCV therapy. This paper provides a review of the neuropsychiatric adverse effects of DAAs and drug-drug interactions (DDIs) between DAAs and psychiatric medications.

Methods We conducted a PubMed search using relevant search terms and hand searched reference lists of related review articles. In addition, we searched abstracts for major hepatology conferences and contacted respective pharmaceutical companies for additional studies.

Results Limited data is available on the neuropsychiatric adverse effects of DAAs; however, data from major clinical trials suggest that DAAs have minimal neuropsychiatric risk. DAAs can potentially interact with a variety of psychotropic agents via cytochrome P450 and p-glycoprotein interactions. Triazolam, oral midazolam, St. John’s Wort, carbamazepine and pimozide, are contraindicated with DAAs. DDIs between DAAs and antidepressants, anxiolytics, hypnotics, mood stabilizers, antipsychotics and treatments for opioid dependence are summarized.

Conclusions Although DAAs do not add significant neuropsychiatric risk, the potential for DDIs is high. Consideration of DDIs is paramount to improving medication adherence and mitigating adverse effects during HCV therapy.

So the abstract  (I saved you from the entire article)  kinda says: We don’t know enough to draw any conclusions so we caution you when using any drugs metabolized by the liver, including antidepressants. Terms: pharmacokinetics (where the drug goes in your body and how your body changes it to water-soluble (pee), or fat-soluble (poop) to get rid of the drug:  pharmacodynamics , what the drug does to your body to heal you and how it does it. This is for one drug. Think about a bunch of drugs where the liver and maybe kidneys do not work well.  There is a traffic jam and a couple of fights at the entry to your liver and the drugs build up in your blood.   Crash.

This is a year of my life

CPY 450 System, took me years

And so I say to you what any good or bad pharmacist would say:  “Caveat Emptor”.  Actually,  the pharmacist will put warning stickers all over the bottle and give you a packet of small print information.  Then she will make you sign that you have been counseled.

Beware the Jabberwok

Caveat Emptor

* A nod to the awesome Robert Earl Keen Jr. http://www.metrolyrics.com/the-road-goes-on-forever-lyrics-robert-earl-keen.html

http://www.hcvadvocate.org/hepatitis/factsheets_pdf/HCV_Neg.pdf  This is awesome for those like me.

http://www.medscape.com/viewarticle/807927?src=wnl_edit_tpal&uac=190805DY

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