Just a brief programming note.  I spent this morning doing a radio interview tour around the country talking about liver disease.  I was working with Ann Moore, a nurse practitioner specializing in liver disease.  We did interviews with 17 internet only  and live radio stations in an effort to educate the public broadly about liver disease, the need for early detection, and the role of the foundation.

Most of the interviews were live to tape so I don't know when they will air, but if you listen to any of these stations perhaps you will get a chance to hear them.

Last year I wrote about an experience I had while out jogging.  I persist in believing that the doctors know what they are talking about regarding exercise and liver disease so it is a subject that comes up from time to time. For anyone who is interested in the challenge of self image versus father time, here is a link to that earlier item which you might relate to.

I was out on the greenbelt yesterday and there is a nice spot near the river where people like to stop and rest or reflect. I had stopped there and a young woman came running along and also decided to take a break.  Surprisingly, she recognized me as the old guy that she had passed last year and we had a few chuckles about the event.

First I apologize if this gets too technical.  I usually try to provide information in some hopefully entertaining way but sometimes I have to dig into the details because they are important.

An article in the current New England Journal of Medicine has this article.

Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts

This demands a bit of background since we are a liver disease group and the report is measuring cardiovascular disease.  There are studies of olive oil and liver disease but generally they are not as long or big as this one and many studies lack the rigor. You should also remember that liver disease is the master of co-morbidity.  It is generally not understood that cardiovascular disease is the number one cause of death related to cirrhosis.

I talk a lot about the problems sugar causes for the body. If you had to pick one reason for why your kid's generation will die younger than yours and be sicker in old age than they should have been you could do worse than pick a soda.  We have a very curious relationship with sugary drinks.  We will happily drink a 16 ounce soda and easily serve it to our kids.  No parent or other apparently rational person will sit down and eat 10 teaspoons of sugar and yet that is a common amount in our soda.

This is a small diversion, but

did you ever wonder how to kill a rat with food?

Remember from prior blogs, that fibrosis forms first as long strings that associate over time and are eventually arranged into a very stable triple helix that is zipped together by vitamin C.  There are many kinds of collagen in your body and they have different characteristics depending on their specific chemistry.  The progress of cirrhosis is determined by how that collagen forms and matures.

As a way to think of it, collagen is a cousin to the plastics that are everywhere in your everyday life.  They are polymers which are large groups of similar molecules that link together.  Like many collagens in the body, those in the liver are flexible and stretchy, think skin as an example, when they are formed.  It is the nature of many polymers to take some time to "cook", that is to form the structure and then to cross connect to other molecules nearby.  They attach to each other in dense mats which leads to the kind of tissue you see in a scar in your skin. It is basically a "mat" of fibers.  As those mats get thicker and stronger they begin to destroy function in your liver and we call that cirrhosis.

So many of us take supplements, pills, potions, elixirs, lotions, bromides, miracle secrets from the ancients, super foods, substances of all kinds, as well as what our doctors prescribe, and with all of them we are told they are good for us.  We are mostly immune to the cautions about side affects and don't even consider how much we don't know as we swallow that bit of magic that will help us be well.

I'm an engineer, not a doctor so I can ask you a what if question, which you, as a smart person can consider.  What if one of the pills that everyone thinks is good for you can kill you by destroying your liver slowly?  Would that be something you would think about?  If you will stay with me here for just a bit I'll tell you a story about how some well intentioned advice may kill you.

In my last note I talked about how collagen forms to become a deadly enemy for your liver.  To be clear collagen is a very good thing.  Much of your body is made of it.  You couldn't exist without a robust collagen process. But like so many things, too much in the wrong place or time and the engine of life starts to fail.

Remember this process where the initial fibers of a blood clot wind themselves into a very tough triple helix which eventually destroys your liver as tough scar tissue?

Sometimes what everyone knows is just wrong.  Can cirrhosis improve? Care to join me for a walk down cirrhosis lane?

First what is cirrhosis? In simple terms, it is the formation of scars everywhere in the liver which causes it to fail.

OK, what then are scars?  We all know them, we can see scars on our body where we have been wounded.

When liver cells are injured the same process occurs as when you cut yourself.  Scar forming processes move in and try to repair the wound. This happens at the cell level so scar tissue forms everywhere within the liver and when it gets bad enough to disrupt the normal function of the liver we call it cirrhosis. That leads to ESLD, end stage liver disease, and death.

So what is a scar really? In the liver, inflammation is a typical culprit.  Something, lets say too much fat or alcohol for example, damage liver cells and some of them die. That degeneration of cells causes clotting processes to start and platelets and the other wound healing chemicals move into the area.  This process is crucial to your health but it is a balancing act.  If the debris removal systems are able to clear out the dead cells all is well and that brief episode of cell death and inflammation is gone and all is well.  Liver cells die by the millions every day and this is the normal process.

An ironic curse with the clear implication that 'uninteresting times', of peace and tranquillity, are more life-enhancing than interesting ones.  Another cautionary message is 'be careful what  you wish for', and yet another 'fools rush in where wise men never go'.

Cliche man is here apparently, but the old warnings aren't necessarily wrong.  I want to let you know that the foundation has entered an 'interesting time'

We have been greatly honored with support and now it is time for us to stop talking and start dancing.  Intercept Pharmaceuticals has agreed to provide the first funding for our screening program and we plan to open our first pilot facility in Houston in the summer.  For those who have joined us recently, we advocate building 400 screening centers across the US and to screen 1 million people a year who are at risk for liver disease from the large co-morbid (people with multiple diseases) population.

When I think about screening for liver disease I often find that tune from My Fair Lady, "Why Can't A Woman Be More Like A Man" running through my mind.

It is an odd mental tick I suppose. One of my favorite musicals connecting to a potentially terminal illness, but the challenge we face as liver patients would largely vanish if only a liver was more like a breast.

OK, I stretch the analogy a bit here but consider how cancer is managed.  We search diligently for cancer and while there are significant differences between cirrhosis and breast cancer the statistics are interesting. There are around 40,000 deaths annually from each disease, but we search out the tiniest incidence of breast cancer that we can find and manage it aggressively but we ignore liver disease until it presents serious symptoms.  Think about that for just a moment.  Why would we test breasts regularly but intentionally ignore early liver disease?

If you think about the co-morbidity illustrated in this image, it is clear that there are at least 40 million Americans who are at some level of risk for developing advanced disease. The question, "WHAT TO DO" hangs there in the face of vast suffering to come.

Studies are coming in as research focuses on liver disease and the challenges that we face.  A whole body view instead of organ by organ is becoming more common which recognizes that the liver is so foundational to health that a very wide range of diseases are co-morbid with liver disease. That is a fancy word that means the problems are related.

The Foundation is patient focused on fatty liver and NASH leading to cirrhosis which is just one of many liver diseases.  The American Liver Foundation covers all liver disease so we are logical collaborators but with a different focus.  I recently joined with the ALF to visit with a number of congressmen about issues of law that we feel are critical to our community.

We are particularly alarmed by recent changes in the rules governing insurance companies so we wanted to take your voice to Washington.  Simply put, government agencies are once again proving that they are inherently a fools paradise and insurance companies are demonstrating that they are unconcerned if you die or are forced into poverty.  As usual, Congress is the gang that can't shoot straight, but the patients are reliably suffering and dying. 

A key goal of ours is education for both patients and physicians. We recently have been working with Intercept Pharmaceuticals to develop materials to help both physicians and patients understand the challenges of liver disease.  The material is being distributed by Healio, as part of its in-depth specialty clinical information for physicians.

I wanted to let you know that the Healio Education Lab,

“Understanding the NASH Knowledge Gaps,” is now live.

TRIAL: A test to determine whether the species will create new organ designs to accommodate chronic over feeding or fail and result in mortality and long term decline.  The alternate endpoint, increased intelligence in feeding strategies.

OVERVIEW;

The test subjects all like sugar but dietary advice mostly says give it up.  The question, what really happens when they eat excess sugar over time?

OK, but sugar is glucose and it is known that glucose is a fundamental fuel so what is wrong with that? Let's take a walk down bio-chemistry lane.  Just a peak so easy peasy. This is really important if one has concerns about livers so don't run away yet.

NASH is the silent stalker.  The hidden instrument of the pain and suffering that is our modern plaque of caloric poisoning. History might one day choose to call this time "The White Death" to balance tales of "The Black Death" of Medieval Europe.  When the mortality statistics correctly include the comorbidities of NASH and cirrhosis, this time will be reckoned as the greatest mass death in human history.  It will be viewed as a strange period when much of the society willingly chose to adopt behaviors that would lead to their early and painful deaths.

Well enough prophecy. It is well established that diet is producing the majority of the liver disease epidemic.  We grow fatter each year and even when we try to change that the cacophony of advice is overwhelming.  Groups are passionate about the extremes of food and you can find advocates for eating all combinations of diets with "expert" advice about high and low fats, carbs, and proteins.  The vegans vs the paleo for example are both confident that they are correct and experts are available to support each group.  There is a great middle, of course, who have no real doctrine and just eat what is convenient and appeals to them, but like a great herd of wildebeest they move always toward the river where the crocodiles lie in wait.

OK, too cute by half I suppose.  However, now that you are here, if liver health is of interest to you let me splain you a little bit about why you need to care about fatty acids and carbon chains.  (eyes glazing over)  Stick with me for just a bit and I'll try to keep you alive.

If you will set aside your concepts of beauty for a moment, understand that you are really an oddly shaped container for a vast army of carbon chain molecules that are connected in various ways and which react chemically in a very flexible manner.  Most of it, while very entertaining, is beyond our ability to perceive or modify but the one thing that we can do is choose what carbon chains we deliver to the odd container that is our body.

The four horsemen of the apocalypse.  The vision of death and destruction for humanity from the new testament is a chorus of the woes that can befall society.  It evokes hazard from all directions bringing misery and the pale horse called death.

When you come to grips with the health aspects of liver disease it is a surprise to learn that our understanding of our bodies as an integrated system is so poorly appreciated.  The mix of chemical processes that are done routinely by the liver cannot be duplicated by our chemists.  It is estimated that over 500 functions are performed by the cells of the liver and they affect every other kind of tissue in the body. Imagine that, all of that activity in a cell about one fifth the width of a human hair.

You may imagine that your brain is the most amazing part of you.  It is entertaining to wonder about how you can wonder about yourself and the mysteries of consciousness and self awareness are worthy of awe but the miracle of your body is really your liver.  I grew up in the computer industry and since I'm not as young as you thought, I remember a time when a single person could actually understand everything going on in a computer.  Today computer systems are so complex that no one can understand it all.  The liver is like that.  Hundreds of interacting chemicals churning through  chains of reactions with a vast number of interlocking functions.  If you examine biochemistry in any detail you have to wonder how it is even possible for you to be alive.

This link below expresses that vision of impossible elegance and beauty to me.  Not my usual story but I invite you to enjoy before you read about the boring stuff to follow.

I've had the opportunity to look closely at some of the research that is going on with liver disease treatments and I really have to admire the teams that are tackling this problem.  The liver cell is rather like a bunch of finely tuned clocks within clocks and if you touch any part of any clock it may stop some other clock from keeping the proper time. The people on the front lines of this research face real challenge, but the good news is that we can now see that there will be successes and cirrhosis may not be the toboggan ride to hell that it is now for too much longer.

Gilead and Intercept are two of the companies who are working hard to develop treatments for liver disease. 

Intercept has been working in the area of PBC, primary biliary cholangitis, which is a disease that attacks the main outlet system of the liver.  One of the key functions of the liver is to make the bile that is responsible for your ability to digest fats.  Their front line product is obetocholic acid which has been granted accelerated approval by the FDA and is now under study for NASH and other liver problems.  Intercept is a leader in the race for some kind of treatment for this category of disease.

Gilead made its bones with Harvoni which cures hepatitis C.  This is an immensely important event because millions of people were doomed to suffer liver disease since hep C was incurable.  Now Gilead is mounting a very important effort to make a similar contribution to NASH and cirrhosis.  Gilead's approach is a bit different from that of most of the industry as they are assuming a multi-drug combination will be the solution. Most companies believe that but are focused on specific single step strategies that likely lead to a cocktail but Gilead's research seeks to build the cocktail from the beginning.

These are just glimpses into the industry and we could look at the 400 or so molecules under study and all are interesting views of how one might attack the problem of liver disease but remember, none of these can be done without clinical trials.  If you have any interest in participating in a trial take a look at our trial tool and see if anything is a match for you.  Here is a link to that system.

Clinical Trial Finder