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

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. 

HEPATITIS C: THE HAPPY-EVER-AFTER ENDING

Happy Ever After, Mostly

Happy Ever After, Mostly

I witnessed a marker for Hepatitis C yesterday that three years ago was impossible. On CBS, Gilead was advertising treatment/cure for Hepatitis C. Consider that three years ago admission of having Hep C was admission of a dark past, even when none existed. Consider that only 20% Hep C positive people even knew their status. Consider that three years ago treatment success was 40-50% even with forty-eight weeks, multiple drugs that were disabling and exacerbated long-term crippling depression. The latest treatment recommendations for hepatitis C virus (HCV) infection are now available on www.HCVguidelines.org, the result of a collaboration between the American Association for the Study of Liver Diseases (AASLD), the Infectious Diseases Society of America (IDSA), and the International Antiviral Society-USA. These are the few that know what is happening. http://hcvguidelines.org/sites/default/files/AASLD-IDSA_PressRelease.pdf   

Drug development for HCV is progressing rapidly, with new direct-acting antiviral medications capable of essentially curing HCV. Eugene Schiff, MD, director, Schiff Center for Liver Disease at the University of Miami Miller School of Medicine in Florida, commented on the development of the Web site in an interview with Medscape Medical News. “The reason [for the development of the Web site] is that the field is moving so rapidly…the [US Food and Drug Administration] is trying to advance some of these [medications] faster than they have traditionally in the past, which is wonderful for the patients,” Dr. Schiff said. “Because of all this, the average clinician can’t keep up with it, and they’re trying to be more in sync with the advances,” he added. “In just the past 3 months, 2 new medications became available for treating HCV that hold a great deal of promise for patients living with this disease, and more are expected. HCVguidelines.org provides physicians with the latest information and informed guidance on the available treatment options based on a rigorous review of data,” Barbara Murray, MD, president of IDSA, explained in the statement. “[The development of newer drugs is] of historical significance. We are quickly approaching 100% cure rates of this disease with treatment,” Dr. Schiff explained. “The presence of a readily available, frequently updated guidance document is a great service to providers and their patients, who will benefit from modern treatments that result in cure of HCV up to 95% of the time,” Michael Saag, MD, a member of the board of directors of the International Antiviral Society-USA and a cochair of the guidance panel, said in the statement. “The site will be updated regularly to keep pace with improved diagnostic tools and new drug options as they meet [US Food and Drug Administration] approval,” according to the statement. The Web site will include an ongoing summary of recent changes. Guidance for Insurance Carriers.   Also The rapid development of medications has made insurance companies as well as clinicians unsure of the best treatment options

The newer drugs are expensive, and not all insurance carriers are willing to pay for them. The guidelines may help insurance carriers evaluate the appropriateness of these drugs for patients with HCV. As the drugs become more available to patients, the cost may go down, Dr. Schiff said.

Even though the newer drugs are expensive, they may still be cost-effective if they are curing patients, he added.

Guidance for Insurance Carriers Also

The rapid development of medications has made insurance companies as well as clinicians unsure of the best treatment options, the statement explains.

The newer drugs are expensive, and not all insurance carriers are willing to pay for them. The guidelines may help insurance carriers evaluate the appropriateness of these drugs for patients with HCV. As the drugs become more available to patients, the cost may go down, Dr. Schiff said.

Even though the newer drugs are expensive, they may still be cost-effective if they are curing patients, he added.

 

 

Hepatitis C: More Affordable Treatment Possible

http://www.medscape.com/viewarticle/819086

This attached link presents interesting models for lowering treatment drug costs.  Not necessarily doable, but interesting.  Remember I worked for drug companies for decades.

Thank You Gilead for GS 5885 /  Solvaldi.  Saved my liver!

Good Bye everyone, thanks for your support.

Special thanks to Jana Lee RN and Advanced Liver Therapies.  Time for you to tackle something else like Non-Alcoholic Fatty Liver Disease or decrease liver transplants rejections; and do something awesome again.

www.HCVguidelines.org  Give this to your physician

http://hcvguidelines.org/sites/default/files/AASLD-IDSA_PressRelease.pdf

http://www.gilead.com/medicines/product-approval-timeline.

 

 

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?

Prometheus Shows The Liver Grows

Prometheus Bound demonstrates what we have known about liver regeneration since fire was first stolen

Peter Rubens, artist

As punishment for stealing fire, Prometheus was chained to a rock and every day a vulture/eagle came and ate his liver.  The liver grew back and was eaten again and again.  Prometheus was the son of Iapetus who was one of the Titans.  He stole the sacred fire from Zeus and the gods. In punishment, Zeus commanded that Prometheus be chained for eternity in the Caucasus. There, an eagle (or, according to other sources, a vulture) would eat his liver, and each day the liver would be renewed. So the punishment was endless, until Heracles finally killed the bird.   by Jonathan Vadakethu

The left lobe of the human liver grows rapidly.  That is why we can take part of one person’s liver and transplant it into person.  Both grow a liver.  So if that is true, why can’t a liver regenerate on its own after injury from hepatitis or cirrhosis?  Try to picture you skin healing after injury.  Now picture skin growth over the scar.  Scar tissue doesn’t grow because it is, well, scarred.  So injured livers do not regenerate.

If I regenerate my liver, do I regenerate my crazies? Not studied, but these guys from the University of Minnesota say volume of liver regeneration is ideal at 3 months for recipient and donor.  Left lobe may be best. 

I just summarized the below study for you in 2 sentences.  I can’t imagine the difficulty a patient without some medical knowledge has trying to make informed decisions about his/her own life. 

Liver Regeneration After Adult Living Donor and Deceased Donor Split-Liver TransplantsAbhinav Humar,1 Kambiz Kosari,1 Timothy D. Sielaff,1 Brooke Glessing,1Maria Gomes,2 Charles Dietz,2 Galia Rosen,2 John Lake,1 and William D. Payne1

As the number of living donor (LD) and deceased donor (DD) split-liver transplants (SLTs) have increased over the last 5 years, so too has the interest in liver regeneration after such partial-liver transplants. We looked at liver regeneration, as measured by computed tomography (CT) volumetrics, to see if there were significant differences among LDs, right-lobe LD recipients, and SLT recipients. We measured liver volume at 3 months postoperatively by using CT, and we compared the result to the patient’s ideal liver volume (ILV), which was calculated using a standard equation. The study group consisted of 70 adult patients who either had donated their right lobe for LD transplants (n _ 24) or had undergone a partial-liver transplant (right-lobe LD transplants, n _ 24; right-lobe SLTs, n _ 11; left-lobe SLTs, n _ 11). DD (vs. LDs) were younger (P < 0.01), were heavier (P _ 0.06), and had longer ischemic times (P < 0.01). At 3 months postoperatively, LDs had attained 78.6% of their ILV, less than the percentage for right-lobe LD recipients (103.9%; P _0.0002), right-lobe SLT recipients (113.6%; P _ 0.01), and left-lobe SLT recipients (119.7%; P_0.0006). When liver size at the third postoperative month was compared with the liver size immediately postoperatively, LDs had a 1.85-fold increase. This was smaller than the increase seen in right-lobe LD recipients (2.08-fold), right-lobe SLT recipients (2.17-fold), and left-lobe SLT recipients (2.52-fold). In conclusion, liver regeneration, as measured by CT volume, seems to be greatest in SLT recipients. LD recipients seem to have greater liver growth than their donors. The reason for this remains unclear. (LiverTranspl 2004;10:374 –378.And this is just the abstract.

The problem with following the literature and medical education is that you know how not good it is.