“Christmas is coming and a New Year is fast approaching. I feel it’s important to begin the coming year with great resolve and hope in our hearts. As I sit here reflecting on the past year, I realize there is much good news to share. Strides are being made in liver disease treatments and the cures are moving at a rapid pace. It’s as exciting as it is rare when a breakthrough occurs in medicine. This past year has seen great advances in Hepatology that are impacting the doctors’ abilities to diagnose and treat liver disease. I’ve hit a few of the highlights below:”

• Hepatitis C -    Worldwide, an estimated 150-180 million people have the Hepatitis C virus (HCV).  Also referred to as chronic hepatitis C (CHC), the virus has usually gone undetected for many years in people until major damage has occurred to the liver. Sometimes called the ‘silent killer,’ those with the virus become candidates for liver transplantation and liver cancer.  Not identified as “C” until 1989, the virus was referred to as non-A and non-B. The only treatment found for HCV was interferon shots and ribavirin pills, these were difficult on the patient physically and mentally, with a low rate of success of elimination of the virus. However, the light is now visible at the end of the tunnel. As written by Yale doctors Kim and Sarkar and published in Hepatology in early 2014:  “Few disease areas have experienced the rapid, paradigm-shifting change in screening, diagnosis, and treatment over the past three years than chronic hepatitis C virus (CHC) infection, and the pace of drug development is unlikely to slow for the next several years.”  2014 has seen that reality with the approval of drugs and a pipeline of additional drugs set for approval which give those with HCV a 90% plus chance of SVR, or sustained viral response.  

• NAFLD: Nonalcoholic Fatty Liver Disease - The pathology, or physiology, of non-alcohol fatty liver disease (NAFLD) is understood so much better, setting the foundation for the development of effective therapy. For example, new research has found that in patients with NAFLD, adiponectin (a protein involved in regulating glucose levels as well as fatty acid breakdown) is a better predictor of subclinical atherosclerosis than are liver function tests. This is because the new evidence suggests cardiovascular disease dictates the outcome in patients with NAFLD more frequently and to a greater extent than does the progression of liver disease.

• NASH: Nonalcoholic Steatohepatitis-  (the progressive form of NAFLD.  Steato means fat and hepatitis means inflammation of the liver). Clinical Gastroenterology and Hepatology published a report that researchers administered Galmed’s aramchol in a 3 month study.  It was found to potentially be a disease modifying treatment for non-alcoholic steatohepatitis.  Aramchol affects liver fat metabolism and has been shown, in a Phase II study, to significantly reduce liver fat content as well as improve metabolic parameters associated with fatty liver disease.  It has also been shown to be safe with no severe adverse effects.  A Phase III clinical trial is planned for 2015.

“But Morgan, what does that mean for you & your friends?” 

“Well Plucky, it means that new research has shown that measuring your cardiovascular health is a better predictor of NASH than measuring your liver health.” 

"Wow Morgan! How is that possible?"

“New technologies are allowing medical professionals, in all fields, to make advances that were not even possible in the past. Can you believe that people with liver disease can be treated with stem cells taken from their own skin or blood?! I even saw a 3D image of me. Plucky, if you will please let me finish I will tell you lots more.”

• CIRRHOSIS-(Damage to your liver as a result of several liver conditions. It cannot be reversed but it can be managed).  New approaches have been developed to manage the complication of cirrhosis. For example, in a study from Amsterdam, The Netherlands last year it was found that non-selective beta-blocker (NSBB) significantly reduce HVPG (hepatic venous pressure gradient), improves gastrointestinal permeability and decreases bacterial translocation levels.  In patients with cirrhosis, increasing blood pressure in the abdominal circulatory system (portal hypertension) leads to potentially lethal complications which might be prevented with simple medical treatment.  Patients with cirrhosis and portal hypertension have increased gastrointestinal permeability which allows the movement of bacteria through the lining of the gut into the blood stream in a process known as bacterial translocation.  Bacterial components can be involved in the onset of complications of cirrhosis.

• HCC- Hepatocellular carcinoma-  In liver cancer research, Arlin Rogers, a pathologist, has found that prolactin, a hormone that helps nursing mothers produce milk, may help prevent liver cancer.  This finding holds promise because drugs that can artificially amp up levels of prolactin have already been approved by the FDA. .

                      

• Tumor Targeting Drugs- New drugs are being developed that work differently from standard chemotherapy drugs.  These drugs target specific parts of cancer cells or their surrounding environment.  Tumor blood vessels are the target of several newer drugs.  Liver tumors need new blood vessels to grow beyond a certain size. The drug sorafenib (Nexavar), which is already being used for some liver cancers that can’t be removed surgically, works in part by hindering new blood vessel growth.  This drug is now being studied for use earlier in the course of the disease, such as after surgery or trans-arterial chemoembolization (TACE).  TACE is an image-guided procedure that is used to treat malignant lesions in the liver. Researchers are also studying whether combining it with chemotherapy may make it more effective.

• BA: Biliary Atresia- In this area of medical research so much more needs to be done. With all the new technologies I am hopeful this will happen soon.  Approximately 80-90% of currently affected infants will survive to adolescence following Kasai portoenterostom- a procedure to allow for bile drainage.  

• Medical Food??-  A study published by the American Gastroenterological Association found that the probiotic VSL#3 significantly improved liver function and reduced the risk of hospitalization. It also reduced the development of hepatic encephalopathy (the worsening of brain function that occurs when the liver is no longer able to remove toxins from the blood). VSL#3 caused no adverse effects. It should be noted that VSL#3 is not a drug but a “medical food” and has not been approved by the FDA. 

• Protecting Your Liver-  In January, the FDA released a highly anticipated statement regarding acetaminophen toxicity and prescription pain relievers.  According to the FDA no pain reliever should be prescribed that contains more than 325 mg per tablet or dosage of acetaminophen.

"These are just some of the highlights of what’s going on with hepatology research.  Liver disease causes tremendous suffering and we are by no means done but there is reason to be hopeful.  In the overall picture of liver disease, I believe the future lies in areas such as molecular biology, stem cell therapy and, 3D imaging.  For years I have heard things like “there is a cure right around the corner” and “tomorrow could bring a new treatment”.  I never really believed that until now.  There really can be a cure and, there really may be an effective treatment!  The quality of life, productivity and potential of millions of people can be much improved through science, research and innovation.  There are so many brilliant and dedicated people working tirelessly to make this happen.  As we head into 2015, there is so much to look forward to.  Let’s all take care of each other and think about our New Year’s resolutions!!"

“Liver, liver, liver.  No matter how many times I say it, it doesn’t sound exciting or sexy.  As I’ve said before, it is the most ignored and one of the most important organs.  It is the only organ in your body that receives blood from the heart and another organ-your intestines.  When I talk about the liver, do people think I said kidney?  I wonder this a lot.  It is probably because it is so complex and involved in so many bodily functions that most people get lost in the minutia.”

Albu what??!!??
 

MORE ABOUT PROTEINS

 In the previous blog, we were talking about proteins that the liver produces.  It got so complicated that I decided to break it down a bit more.  So, today I’ll be talking to you about the most important and the most abundant of the proteins:

ALBUMIN

Albumin is the major protein in plasma.  Plasma is the liquid component of blood, where the red blood cells, white blood cells, and platelets are suspended.  Plasma constitutes more than half of the blood’s volume and consists mostly of water that contains dissolved salts (electrolytes) and proteins.  Albumin performs many function including helping to keep the fluid portion of your blood within the blood vessels, and helping to transport drugs and other substances by way of the bloodstream. Albumin plays an indispensable role in maintaining the delicate chemical balance of the nourishing interstitial fluids that surround and support the trillions of cells in your body. Interstitial fluid is a thin layer of fluid that surrounds your body’s cells.

  It acts as a kind of fueling station in terms of nutrients for our cells.  Interstitial fluid contains glucose, salt, fatty acids and minerals such as magnesium and potassium.  This fluid can also hold waste products that result from metabolism.  If these fluids are healthy, your cells will flourish. But if the fluids become polluted, or depleted of certain substances, your cells cannot help but fall ill, and disease will sweep through the body 

Albumin has been described as a "portable liver" because your liver is your body's chief mechanism for disarming toxins and other dangerous substances. Albumin, which is made in your liver, does the same throughout the body. It's as if your liver has sent millions of tiny pieces of itself to every single little cell, to round up and destroy harmful substances and organisms.  Albumin is like a filter that removes toxins from water, like the net that scoops debris out of a swimming pool, or the dispenser that squirts vitamin D into milk.   It ensures that bodily fluids are clean, filled with nutrients, and properly balanced. And when you're filled with health-giving fluid, you cannot help but be healthy.

THE BODY INVADERS

The battle against what Morgan refers to as “body invaders” is protein based.  The immune system utilizes many protein-based substances to fight off the invasion by rapidly producing more protein-based substances to defend the body.  But, there can only be a certain concentration of all proteins in the body.  When the concentration of immune system proteins goes up, the concentration of other proteins must fall. 

One of the proteins that decreases when the immune system is engaged in battle is albumin, and that’s where the trouble lies.  Temporary drops in albumin levels are necessary and not a problem.  The problem comes when you are continually battling invaders and your albumin runs low for months on end.  When the level of albumin in your blood is low, it is a good indication that your liver is not working properly.  The normal level of albumin is between 3.5-5 grams per deciliter (g/dl).

Albumin levels drop when the immune system engages in a battle with invading bacteria, viruses, fungi, inhaled toxins, dangerous substances you eat or drink or, that get in through your skin, respiratory system, and “other” ports of entry.   But, there are some things that can artificially, or temporarily, lower your albumin level such as the level of hydration in your body, dehydration will cause fluctuation in albumin.   Also, malnutrition-not getting enough protein in your diet.

Albumin’s many important duties:

·         Protecting easily damaged tissues from the free radicals (we’ll go into these a bit more at a later time) that can destroy your cells and cause cancer by altering your cellular DNA

·         Guarding against heart disease by transporting the antioxidant vitamins that help keep your coronary arteries clean, binding up fatty acids that tend to clog your arteries, and stabilizing  the ratio  between HDL (good cholesterol) and LDL (bad cholesterol).  

·         Binds up waste products, toxins, and dangerous drugs that would otherwise damage your body and encourage disease.  It also detoxifies the interstitial fluid surrounding cells.

·         Protects your biological terrain by buffering your blood against pH changes (pH is a measure of acidity).

·         It helps keep your blood flowing smoothly by preventing red blood cells and other substances from clumping together.

·         It is essential for transporting vitamins, magnesium, copper, zinc, bilirubin, uric acid, sex hormones, thyroid hormones, other hormones, and fatty acids throughout your body.

·         It regulates the movement of nutrients between your blood and your body’s cells.

·         Stabilizes your red blood cells and growth hormones.

·         Plays a major role in controlling the precise amount of water in various bodily tissues.

·         Plays an important role in transporting and circulating reservoirs of thyroid hormones.

·         Purifies the cerebrospinal fluid, nourishes brain cells, and maintains your blood-brain barrier.

·         Helps to ensure that there are adequate amounts of certain key minerals in your bones.

·         Binds and transports the “stress hormone” cortisol, reducing stress-induced damage to the thymus gland, brain, and connective tissues.

“The reason I’ve gone into this crazy discussion about albumin is because of how important it is to your body and mostly, because when your doctor orders blood work, one of the many things you will see is ALB-albumin.  I want you to know how to interpret it.  Be aware, that just because your albumin level is in the normal range doesn’t necessarily mean that your liver is healthy and happy.  In some instances, your albumin can remain in the normal range until your liver is severely damaged-perhaps beyond repair.  So, as I always say LOVE YOUR LIVER!”

Morgan

Morgan here! 

“I’ve been doing a lot of reading about the proteins I produce and what they do.  This stuff can be so complicated that you almost need a medical degree to understand it.  Macrophages phagocytize what?!!?  I’m a liver, not a brain!  But, this is what I’ve come up with: 

I produce many proteins-

• Each protein does a different task;
• Each task is very specialized, but
•  All tasks are very similar.

Class Again???

Kind of sounds like a riddle but I’m going to break it down for you the best I can.” Here I go:

Proteins are molecules made from tiny building blocks called amino acids and are a vital part of all living things.  Protein builds, maintains, and replaces the tissue in your body.  Your muscles, your organs and your immune system are made up mostly of proteins.  They are essential for life.  After water, protein is the most plentiful substance in your body.

Proteins Produced By Your Liver

Albumin – The most common protein found in your blood.  It provides your body with the protein needed to both maintain growth and repair tissues.  Inflammation and infection will cause an albumin level to drop. Albumin helps retain calcium in the blood stream and regulates the movement of water from your bloodstream into your tissues.

Globin- One of the two components that form hemoglobin (hemoglobin is the oxygen-carrying substance in red blood cells).

Globulins – A group of proteins that includes antibodies.  These are the proteins that make up the complement system (a part of the immune system) that combines with antibodies to fight invading microorganisms.

Alkaline phosphatase (ALP) – A protein found in all body tissues.  Tissues with higher amounts of ALP include the liver, bile ducts, and bone.  Blood levels may be increased in any liver disease, but more markedly with cholestasis (a stoppage or slowing of the flow of bile).

Alpha 1 (AAT) – Plasma protein that inhibits the activity of trypsin and other proteolytic enzymes (these enzymes facilitate the breakdown of rouge proteins in your bloodstream and in the soft tissue of your body.)  The main function is to protect the lungs from inflammation caused by infection and inhaled irritants.  Inherited deficiency of Alpha 1 leads to emphysema and sometimes cirrhosis.

Antibodies – proteins produced in response to a foreign and potentially harmful invader. They have a special shape, and combine chemically with these substances to flush them out of your body.

Ceruloplasmin – Copper transporter protein.  It also plays a role in iron metabolism.  This protein transports 95% of  the copper in your blood plasma.  Copper plays an important role in the body by aiding important bodily processes, such as producing energy, forming connective tissue, and helping the central nervous system function.

Aminotransferase- A hepatocyte enzyme that modifies proteins (hepatocyte is a cell of the main tissue of the liver).  Blood levels increase in the setting of hepatocyte death.  The two aminotransferases important in liver disease are AST (aspartate aminotransferase) and ALT (alanine aminotransferase). AST is normally found in a variety of tissues including liver, heart, muscle, kidney and brain.  It is released when any one of these tissues is damaged.  For example, AST level in your bloodstream is elevated in heart attacks or muscle injury.  It is therefore, not a highly specific indication of liver injury as its elevation can occur as a result of other injured tissues.  ALT is, by contrast, normally found largely in the liver.  This is not to say that it is exclusively located in the liver, but that is where it is most concentrated.  It is released into the bloodstream as a result of liver injury.  Thus, it serves as a fairly specific indicator of liver status. (Plucky reminded me that I need to reference MedicineNet.com, November 8, 2014 here)

Prothrombin – A protein that helps to clot blood.  A prothrombin time test measures how much time it takes for a person’s blood to clot.  The normal time needed is between 10-15 seconds.  A longer prothrombin time can be caused by a number of things including serious liver disease, a lack of Vitamin K, blood-thinning medication or certain bleeding disorders.

 

“WOW! That was a lot to learn! I’m tired from just reading about all that goes on inside of me. And, I’ve just been told that by no means is this a complete list of all the proteins I produce.  Did you know what happens to my production  of one of these proteins if you don’t drink enough fluids? (no, beer doesn’t count as a fluid). OK, I’ll let you think about that one cause enough for today. I’ll  cover each in more detail in my future blogs.”

Mogan

Morgan here with my second lesson.  It's all about digestion and how essential I am to this process  As I said before, I am your inspection station.  If I'm not healthy or being over worked, I can't perform my job properly.  I've included an illustration of the human digestive system.  That's me up top-the darker purple organ.  Your stomach is to my left and below me.  Your esophagus is the little tube connected to your stomach.  The small, lighter colored organ is your gallbladder-it sort of looks like a pea attached to me. Right under your stomach is your pancreas-it looks like it's being strangled by your small intestine.

 

PART TWO – THE THREE MAIN FUNCTIONS OF YOUR LIVER

1.        It digests stuff

2.        It produces proteins

3.        It gets rid of stuff

Digestion Process

First of all, digestion is the process of breaking down foods and beverages into tiny particles your body can use for energy and to build and nourish your cells.  There are 6 primary processes of your digestive system.

1.        Ingestion of food/beverage

2.        Secretion of fluids and digestive enzymes

3.        Mixing and movement of food and wastes through the body

4.        Digestion of food into smaller pieces

5.        Absorption of nutrients

6.        Excretion of wastes

The Liver’s Job

The digestive process happens in the mouth, esophagus, stomach, intestines then the liver, gallbladder and pancreas.  The main function of the liver in the digestive process is the production of bile and it’s secretion into the small intestine.   The liver is where everything gets inspected and classified as either helpful or harmful.  The nutrients are then transformed into a different biochemical form either targeted for absorption or waste.

Liver cells convert cholesterol into bile acids.  These then mix with more cholesterol, other lipids, electrolytes, water and the waste produced from the breakdown of old red blood cells (bilirubin).  The liver secretes the bile through the bile ducts to your gallbladder.  The gallbladder is sort of a holding tank keeping the excess bile until the partially digested food from your next meals enters your small intestine.

Bile acids are unique because they can mix with fats and mix with water‐this makes them a lipid.  As the bile enters the small intestine, it mixes with the fat particles in the partially digested food.  It breaks apart the large fat globules into tiny fat droplets that float in the watery intestine contents. The way bile acts on fat is very similar to how detergent breaks apart grease.  Enzymes produced in the pancreas and small intestines can then digest the tiny fat droplets into fatty acids your body can use.  So, once the food has been reduced to its building blocks and the good stuff has been separated from the harmful stuff, it is ready for the body to absorb.

What Does That All Mean to Morgan?

If you go out and celebrate or, just stay home and drink all night, I will be working continuous overtime trying to get rid of all that alcohol.  I’m the only organ in charge of processing alcohol and detoxifying the blood.  Breaking down your alcohol is only one of more than 500 vital functions I perform.  I don’t really have a lot of time to do this.  This means that I can only handle so much alcohol at once – I’M BUSY!!!!  If you overload me, the excess alcohol will end up circulating in your bloodstream affecting your brain, heart and other tissue.  The consequences of this is the destruction of my cells, build-up of fat deposits which clogs the flow of blood (remember I’m mostly airy space).  This could all result in fatty liver or, even more serious, inflammation (alcoholic hepatitis) and permanent scarring (cirrhosis) and God forbid, liver cancer!  All I’m trying to say here is to drink responsibly and love your liver (me). 

Love Your Liver

Morgan da Organ here.  In my recent travels, I was surprised to learn that the majority of the people I talked with really didn't know that much about me. I am going to tell you all about myself.  Where I'm located, what I do, how to keep me healthy and what happens when I'm not healthy.

THE LIVER - YOUR VERY OWN BORDER PATROL


The liver is considered as vital on organ as the heart and the brain.  It supports near
ly every organ in the body in some form yet we don't give it much thought at all.  It is a large reddish-brown glandular vertebrate organ that is located in the upper right portion of your abdominal cavity immediately under your diaphragm.  Some say it is shaped like a football, some say it is shaped like a boomerang.  It is one of the largest organs in your body, second only to your skin.  It weighs approximately 3.2 lbs. and plays an integral part in keeping your body free from dangerous aliens.  It literally serves as your body's very own border inspection station.  Virtually every nutrient we consume, whether it has a valid passport or not, must pass through the liver so it can be transformed into a different biochemical form.  That transformation is what allows the nutrients to be used, transported to a different location or stored as an extra inch of fat on your thighs.

Blood flows into the liver through 2 large blood vessels.  The hepatic artery brings blood, rich in oxygen, from the heart and the portal vein, rich in absorbed food material, from your gut.  All the blood that has come from your small intestines flows through your portal vein in your liver, so almost all of the nutrients you eat have to pass through the gauntlet of the liver before heading to the heart for generalized distribution.  Your liver decides what gets kept out, what gets patted down and inspected, and what's allowed to be distributed throughout your body.

Within your liver there is a network of bile ducts (bile is a greenish liquid that helps break down fat).  Your liver uses bile to clear bilirubin from your blood (bilirubin is a substance that comes from the break up of hemoglobin in dead red blood cells).  An increased level of bilirubin leads to jaundice-a yellowing of your skin and eyes.  Your eyes are where it's detected earliest-a sign of most liver diseases.

This was a brief overview of what I am and what I do.  I'll go into more detail in the next segment about the 3 main things I do.

Morgan da Organ

www.facebook.com/orangeisthenewliver