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

Research results can seem like an endless stream of shiny baubles that mean little to you as someone trying to find meaning.  It is an avalanche of data that confuses more than it informs.  But sometimes a vision materializes which carries the piece of the puzzle which brings clarity and useful knowledge.  This study is one of those and you need to understand it if your health matters to you. I'll discuss it below but here is a link.



OK, my wife thinks I can be a drama queen and she points out that I've had this information on our website for almost a year.  We advocate for the use of monounsaturated fat as the main dietary fat and olive oil specifically.  I'm like a reformed smoker who regales everyone about smoking, but I learned late that life and death can hinge on the molecules that you choose to be made out of.

Overly dramatic perhaps, but if you value having less illness pay attention. If not don't bother with understanding this.  Remarkably, this study is about actually producing images of the effect that different kinds of fats have on a critical structure of our cells called the endoplasmic reticulum, or ER for short. 

This is why you care. You live or die based upon whether your cells are able to process the chemicals you require to live.  Obvious but it is that simple. Well, how do they do that? If you imagine a cell as a factory filled with makers you can imagine that some of those sit on the factory floor and don't just float around.  The ER is rather like a factory floor. It is a complex surface inside a cell which gives the systems that make things like proteins and lipids a place to be.  It is the scaffolding upon which the chemical factory that is a cell depends.

OK, so why does it matter what kind of fat you eat?  It turns out that the ER is largely made from the raw material in fats and saturated fats are stiffer than unsaturated fats. While they can be used to build the ER those made of saturated fats are less fluid and the saturated molecules tend to clump together so that there are islands of stiffness in the ER.  To put it simply, that is a less efficient arrangement and your health is affected.

It is common advice to limit your saturated fat intake but it is often not really taken seriously and some diets are flagrant abusers of that advice. As you consider how you want to live consider now and then your ER, the factory floor upon which your very life depends.

Interesting news from a clinical trial about NASH.  There is a lot of research going on for a way to treat or prevent cirrhosis.  Millions of us are headed to a bad end from liver disease but treatments have been elusive despite massive efforts.  It is still early but we may be seeing that hoped for light signaling success.

Galectin Therapeutics just released the result of a phase 2 clinical trial of a drug aimed at cirrhosis which reports positive effects.  It is the first trial result directly targeting cirrhosis that is likely to proceed to phase 3 trials and could be the first treatment to come out of the pipeline in the next few years.  They have a lot of work to do yet but the results today are encouraging.  They have demonstrated the ability to reduce the development of esophageal varices resulting from the increasing portal vein pressure resulting from advancing fibrosis.

WOW, too confusing. A little background perhaps. As damage becomes worse in the liver the pressure in the veins sending blood into the liver increases.  The veins of the esophagus, the throat, are connected and they are weaker so more pressure means those veins bulge like a balloon and are called varices.  Varices are a clear indication of serious liver disease so they indirectly measure overall liver blood flow.  If you do something which results in fewer varices you know that you have affected the liver even if you don't know exactly what you did.

OK, but anti galectin 3 seems kind of weird.  Well let me splain you.  In our body we have a family of 14 related proteins which are called galectins.  The chemistry of proteins is really complicated but they are everywhere in your body and are involved in a vast number of functions.  It turns out that galectin number 3 is associated with several not great things like cancer, inflammation, fibrosis, heart disease and stroke.  So a drug that blocks galectin 3 would be called an "anti galectin 3" and that is the kind of molecule used in this study.  Easy peasy if you say it quick.

This result is important because, even if the exact cellular activity is still under study, we have a molecule that has so far been shown to be safe and that has at least slowed the development of fibrosis in a year long very professional clinical trial.  There are a couple of other drugs advancing through trials at a similar pace but this is the first that works in this way and shows real promise as a drug that might be useful to stop fibrosis before it reaches serious levels.

This isn't a therapy, but it is a good step forward and we can hope that phase 3 trials leading to a useful treatment begin soon.  Also, remember that this is just one of hundreds of molecules being evaluated.  One of the biggest roadblocks may turn out to be a shortage of people willing to participate in clinical trials.  We are partnering with Antidote to provide a clinical trial finder on our website that you can use if you are interested in being involved.  We urge you to consider being a trial  participant as that is the only way that new treatments can come to clinical use.

fattyliverfoundation.org/clinical-trial-finder

A small bit of history, but I tried to get into this trial last year but I didn't pass the qualification tests so they didn't take me.  People tend to be afraid to participate in a trial but actually having really close medical monitoring is a good thing and trial participants generally have fewer problems than those who stay on the sidelines.  Just sayin.

When your liver isn't healthy a lot of bad things happen to other organs.  Just one example is that your digestive system doesn't work well and as the liver loses function ammonia can cause mental problems. When you get hepatic encephalopathy, HE, the treatment is lactulose which is an indigestible sugar.  Its main purpose is to provide a source of food for bacteria in the colon.  If you can grow a good crop they will make the colon acidic which traps the ammonia in an insoluble form so it is taken out of your bloodstream. Few people like lactulose and the side effect of lots of diarrhea doesn't make many fans so is there any way to help that isn't hard to take?

Maybe a bit of chemistry might help.  If you cook a starch like rice or potato in water then cool it and let it sit overnight part of it turns to what is called resistant starch because it isn't digestible by the enzymes in the small bowel.  The starch molecule combines with the water to form a type of crystal that is tougher than the original starch.  The good news is that it is usable by the colon bacteria as food in much the same way that lactulose is. It doesn't mean you can just eat rice and give up lactulose but it may allow you to use a lower dose and if you don't yet have HE a little rice may help you keep it that way.

So why Uncle Ben's.  Hardly anyone knows it but Uncle Ben's converted rice is preprocessed to be a resistant starch and is healthier than the ordinary rice you see.  You can read about it here if you wish wikipedia.org/wiki/Parboiled_rice.

So Uncle Ben is your friend if you have or fear HE.

That's the good news.  Now some disturbing info from the recent Liver Meeting of the AASLD.  A study was done taking 200 generally available supplements from a health food store and testing them to see if they actually had what the label said.  It turned out that 69% couldn't be shown to have the ingredients, or the amounts, claimed on the label and some of the material was toxic to the liver.  You aren't going to get specific names or brands because that just sets off a storm of lawsuits but the work was done by real researchers in real labs.  Make of it what you will, but understand that there are makers of dietary supplements who don't care at all if you die so long as you buy their stuff.  I don't intend to suggest that they are all dishonest parasites but don't think for a minute that just because it has an impressive label you are getting what it claims.

Your best defense against liver disease is a good diet.  If you want to know more about that you might start with this link.
Compare Diets and other helpful information.

I recently attended the meeting of the AASLD, the American Association for the Study of Liver Disease, which is a group of world leaders in research into liver disease.  I was very encouraged by what I heard there and I've been wondering how to explain that to the community dealing with disease.

Fatty liver has mostly been dismissed as a medical problem because it was often benign and even if it wasn't there was no treatment anyway so dealing with it was a matter of waiting until some organ showed symptoms and  try to deal with those until you die.  Many doctors today leave their patients with that feeling of hopelessness with the phrase, I'm sorry but we have no treatment.

There are two very important points that I want to make.  First, it isn't correct to say there is no treatment.  Diet and lifestyle have been well proven to be treatments and there is a lot of information on our website about diets.  If you want to review, here is a link

http://www.fattyliverfoundation.org/diet_compare

More importantly, we live in a very fortunate time because medical knowledge is advancing at a torrid pace.  I've struggled to put that into perspective and decided to relate a discussion I had with Dr Peter Traber, the CEO of Galectin Therapeutics, one of the companies researching liver disease treatment.

Dr Traber is also the author of the blog, LiverLine, which I suggest you read.  It is excellent.  He was relating the changes in health care over his career.  His example was Hepatitis C.  When he began his career the virus was unknown.  Over the course of several decades it was discovered and even though it was very difficult a cure was developed and now we can defeat that disease.  His observation of the state of liver disease research is that we are now on the brink of developing real treatments for liver disease.  Even a veteran researchers like him is impressed by the speed and quality of the work being done on  liver disease today.

There are over 400 drugs being actively evaluated and only a few will turn out to be of value but the research community is confident that they now know enough to be sure that we will get useful therapies in the next several years.  The message for current patients is that for now diet and exercise are your only friends but help is on the way so a hopeful attitude is also part of the therapy.

The discussion below came from an article in our newsletter about brain fog due to hepatic encephalopathy, or HE, which is a challenge for anyone with cirrhosis.  An issue for a patient or a caregiver is that it can come and go and patients can find themselves away from home and in trouble as the ammonia disrupts your cognitive functions.  You can seem demented or on drugs to others.  That can be a life threatening situation so we advise patients with advancing liver disease to get a bracelet or some kind of wearable sign that can inform others what the problem may be.  There are a number of alternatives, but the one we like is MyID.  Here is a link to their site.

https://shop.getmyid.com/pages/learn-about-myid

The reason we like it is because it provides more than just a message.  It also provides a way for the police, EMT's or docs to get your medical information online.  You can store your medical data for free and make it accessible for your care team.  This is a big benefit to just having a warning label.

The rest of this is from our newsletter as a little background about the problem.

I recently returned from the annual meeting of the AASLD.  This is the association of the real liver disease experts and the very top of the profession attend and speak about the current research.  If music is your thing, often, the little side notes are as interesting as the majesty of the main orchestra.

An unappreciated aspect of advancing liver disease is that the liver, as the real guardian and engine of the body, takes its job seriously.  Did you ever wonder what extremes the liver will go to in order to maintain your life?  Can you imagine that it will actually eat your muscles if necessary?

An example that is easy to visualize is what happens to prisoners of war who are not fed.  We have all seen pictures of skeletal people reduced to a shadow of themselves by starvation.  Imagine that process as an aspect of liver disease.  We are all familiar with the frailty that tends to come to the very old.  Frailty is actually a medical condition that is involved with a number of processes.  But what if you are not extremely old, how might that affect you?

If your liver is not operating properly one of the organ systems that can be affected is your digestion.  There is an intimate dance that takes place between the bowels and the liver.  When food is digested and nutrition moves into the cells of the bowel it very soon must pass through the liver where the biochemical magic takes place.  A lot of chemicals are involved and some important ones are amino acids.  These are the building blocks for a host of critical functions of the body.  So imagine what happens if your diet is deficient or your digestive system is compromised so that the liver is unable to get the amino acids it requires.

What to do?  Well, the liver, being resourceful sends hunters out to get what it needs.  Fortunately the muscles have useful materials so the liver takes what it needs and the muscles are reduced.  The liver effectively eats the muscles if necessary to maintain life.  Clearly that eventually leads to the same kind of frailty of extreme old age even in younger people.

So, can that apply to you if your liver isn't tip top?  Indeed it can.  Here is an example that might give you a mental image.  For someone with a compromised digestive system that is not operating at a normal speed, overnight is metabolically the same as a 3 day fast.  So every night your liver may go looking for some nutrients and harvest them from your muscles.  The medical term is sarcopenia, but it is essentially muscle wasting and fatigue is part of the process.

As a patient, what can you do?  As a practical matter diet is the main tool.  Taking some nourishment later in the evening, like a can of Ensure at 10 o'clock to break the fast cycle and soothe the liver's need for nutrients will help.  It will also help to add branched chain amino acids to your supplements.  This is what body builders use to grow big muscles but 4 grams a day is sufficient.  It doesn't take a lot.  They are called BCAA and are available online or at any store that sells supplements.  These are important because they are basically predigested and easily used by the liver.  I don't generally suggest supplementation but the mortality risk associated with frailty is serious and something that liver patients need to be aware of.

If I was inclined to become a preacher needing only a miracle to fill my heart with wonder the liver cell would become my guiding light. Behold the single most important cell in your body, the key to life as you know it.

How can that be you ask.  Surely the heart or brain is of far more value.  No one cares about the liver.  Who ever heard of a march for liver, and  that brown is a crappy color for a tee shirt.  No one signs up for a fun run for fatty liver.  Liver lover just sounds peculiar.  You say "that's not promising as the guiding light for a preacher man".  You are inclined to offer kindly,  "don't give up your day job".

Sadly, it is true that the liver sucks as a symbol for a popular movement but real truth and glamour are not often riders on the same train.

There are so many things about the way we deal with health in general and liver disease specifically that get my goat that the poor thing has the blind staggers from all of the abuse.

Our society has become a case study in death by excess.  We have too much food, too much leisure, too much convenience, too much marketing, too much image manipulation, too much feckless government, too much misinformation, too much profiteering.  I should stop as I've probably already said too much.

Our focus here may seem too limited to justify sweeping comments like this.  It paints me as a wild eyed crazy man for some. In my defense, my perspective comes from the very un-glamorous view from the liver.  Since there have been no treatments for the most common cause of liver failure and death, the glamor diseases like diabetes, heart failure, cancer, various genetic problems, and so on get the attention.  The problem, in its simplest form is that the liver is like an abused but uncomplaining spouse who lives under constant threat but perseveres in silence.  Our body is bio-chemically very complex and could not exist without the quiet workhorse that is the liver going about its 500 or more jobs.

Think of that.  A liver cell that is about one fifth as wide as a human hair is constantly involved directly or indirectly in 500 different functions and you will suffer some health consequence if any of them are not done.  This also explains why we have no treatments.  It is so complex that we simply have not had the ability to act against a problem without doing harm somewhere else. I'll expand on this in a future article but for now just keep it in mind as you think about liver disease.

I'm optimistic that a new goat will have a better chance.  There is a tremendous pressure for more and better patient advocacy and it is happening when medicine is simply exploding with innovation and discovery.  We have a vast array of current problems to deal with but I am convinced that we are on the brink of a golden age for medicine and patients.  Our biggest challenge will be taking what we know and delivering it in a useful way to the population as a whole.  A key to that will be patients who are engaged in their own care and who actively participate as their own advocates.  It will not always be pretty but the future is bright in spite of the great confusion within the government right how. 

Much of our effort in the foundation so far has been focused on the details of the disease process and ways to combat it.  This is similar to so much that is published today as it avoids the emotional/psychological barriers that make it so difficult  to manage weight in our society and the burden it imposes on the obese.  Our culture is schizophrenic in its pursuit of excess and its glorification of physical perfection.  We are witness to the epidemic of obesity and we tsk tsk over the problem which is abundantly clear in the statistics.

Ignored in these statistics is the pain that burdens those who embrace the excess but fail the image test.  Consider the challenge for fat young people.  Consider the social pain of the young boy too fat to compete or who becomes an object of jokes, even if not deliberately cruel, as he struggles with young angst.  Or the young girl who ashamedly seeks clothing to hide rather than enhance her image lest she be shamed by her companions.  The scars that are produced by young rejection and alienation are lifelong burdens that those who don't fall into that group are unaware of and mostly uncaring about.

However, for many the deck is stacked against them.  It is clear that the one to five pounds a year that we gain as adults imposes a price that our two oldest generations are starting to pay as the obesity driven diseases inexorably engulf us.  But consider the fact that a fat child was uncommon forty years ago but today we have a significant number of people in their 20's already with fatty liver disease. They are bombarded with the images of fitness and health and thinness that are perfection and out of reach for most.  When they try to lose weight they frequently fail or regain what they lose in a soul crushing cycle of failure.

Paradoxically we are surrounded by the supersize culture of food everywhere, serving size calories beyond any rational level.  The dietary practice of our society has become a theater of the absurd.  Absent a desire to harm another what rational person would promote drinking a gallon of soda a day?  What merchant would offer a single serving with enough calories for two days?  What government would promote a diet used to give lab animals terminal disease?  And yet that is the culture our children live in.  Those who are taken by the calorie beast will pay a price in health and happiness for their entire lives.

This is a dialog that we certainly don't have an answer for but it is one that a rational society would engage in and work toward some wiser course.  We know the outcome of our current course, but will we find the collective will to be serious about finding a better way?  Sadly, you rarely lose by betting on the foolishness of the culture.

It will be a busy fall so I thought a review might benefit the newer members and hopefully our veterans won't mind.

Earlier in the year the Stanford MedicineX conference offered us a chance to make a poster presentation at this year's conference.  At the time my mother was dying of lung cancer so I couldn't consider the offer.  For any who would like to revisit the story of a spunky old lady who helped inspire the foundation, here is a link to a vignette of her story as she became a skydiver following a cancer diagnosis at 91.

www.fattyliverfoundation.org/skydive_1/

But, that is a digression.  The MedicineX conference is the subject here.  I was quite surprised when Stanford offered me a free pass to the conference, so unexpectedly I'll be attending.  MedicineX is an ideal platform for us as it seeks to bridge the divide between patients and the profession. Here is a link if you are interested.

medicinex.stanford.edu/about/

To put that in perspective recall our mission is this:

To identify unsymptomatic, undiagnosed Americans with liver fibrosis or early cirrhosis caused by fatty liver disease, and to educate them on the lifestyle changes needed to halt or minimize disease progression.

Our foundation is one of a very few national advocacy groups dedicated to NAFLD.  That focus brought us to the attention of Intercept Pharmaceuticals.

interceptpharma.com/about/

Intercept has given us a grant to attend the AASLD, American Association for the Study of Liver Disease, in October which is the key professional group managing liver disease.  We will be joining Intercept in their efforts to connect to those in the patient community who are facing fatty liver disease.  There are more events this fall and I'll update you as we go along but this threatens to become overlong so I'll close for now.

Hope you are as well as you can be.

Does this surprise you?  A study in Gastroenterology showed that in 2013 NAFLD became the second leading liver disease among adults waiting for a liver transplant. “From 2004 to 2013, NAFLD as an etiology of liver disease for new transplant waitlist recipients increased by 170%

https://www.healio.com/gastroenterology/liver-biliary-disorders/news/print/healio-gastroenterology/%7Ba9c2ec3b-6c46-4c61-a584-f4600e22b305%7D/cirrhosis-now-linked-to-nafld-presents-management-challenges?utm_source=selligent&utm_medium=email&utm_campaign=gastroenterology%20news&m_bt=1156535706095

Chalasani said cirrhosis itself is not difficult to diagnosis in most people, as diagnosis is based on blood work, a physical work-up and cross-sectional imaging such as liver ultrasound or CT scan. Occasionally, though, a liver biopsy may be warranted.

FibroScan (Echosens) is a new technique that helps manage patients with chronic liver disease and cirrhosis. “This is point-of-care testing that can be done in the clinic by non-physician technicians,” Chalasani said. The scan provides both a liver stiffness score (a marker of liver fibrosis) and a controlled attenuation parameter (AP) score (an estimate of liver fat quantity). “The higher the scores (eg, greater than 14-15 kPa), the more likely an individual has cirrhosis,” he said.

Janardhan said that by removing the source of the inflammation that leads to scar tissue formation in the liver, some of the scar tissue might get better. “However, there is a point of no return,” he said. “When a patient develops decompensated cirrhosis, it is very difficult for that liver to improve to the point where the liver can completely repair itself.”

Janardhan said the 10-year survival for a patient with compensated cirrhosis, and who remains in a compensated state, can be up to 75%. “This pales in comparison to a person with decompensated cirrhosis, for which the survival rate is less than 25%,” he said.

This is a fairly long article but worth your time if you are interested in liver disease as I've written here in multiple posts.

Historically fatty liver was viewed as being mostly benign.  The theory was that while liver fat might make the organ vulnerable to other problems it was, after all just normal fat.  This view naturally led to medicine focusing on other problems where symptoms existed.  I thought that view made little sense if only because fat people died younger but the science wasn't there so that remained the story.

Research is now coming out which shows that a fatty liver is an active cause of disease in other organs.  Did you ever wonder why people frequently get fat then get type 2 diabetes? Consider all the effort devoted to diabetes in the management of the symptoms and the long term medical needs.  German research has now shown that a fatty liver begins to produce different secretions, such as one called fetuin-A, into the blood stream.  Those substances enter other organs and trigger reactions there.

This image from IDM shows pancreatic islet cells surrounded by fat cells.  The study was reported in Science Daily at this link but I'll summarize it below.

https://www.sciencedaily.com/releases/2017/08/170818102308.htm