FACTS ABOUT
THE LIVER

FACTS ABOUT THE LIVER:





There remains a great deal yet to be discovered, let alone perfecting the understanding of what is known.

Weighing three to five pounds, in adults, the liver is the bodyʼs largest organ and is essential for maintaining homeostasis in all of the 50 trillion cells in your body. In a newborn, the liver constitutes five percent of the body weight compared to two percent in an average adult. It uses twelve to twenty percent of the bodyʼs total energy. This “alchemical wizard” of the body routinely performs over five hundred known functions to regulate cellular metabolism. It transforms toxins into harmless chemicals for excretion, and digestively absorbed nutrients into usable biochemical forms for cellular function. The body depends on the liver to regulate, synthesize, store, and secrete many important proteins and nutrients. It purifies, transforms, and clears toxic or unneeded substances. The liver itself, is probably the organ most assaulted by toxic modern lifestyles that are based on pollution, stress, junk foods, drugs, etc.

There are four general functions that categorize the liverʼs vital role in regulating complex functions essential to sustaining life:

1. Digestion of nutrients and fuel
2. Production and transport of life sustaining substances
3. Catabolism and conjugation of drugs and other chemical compounds
4. Detoxification and excretion of potentially harmful substances

Some of the critical tasks included in the above cited functions are:

• Production of complex life-sustaining proteins
• Storage of carbohydrates and reserves of critical vitamins and minerals such as iron
• Regulation and storage of lipids
• Production and regulation of components of both the coagulation and fibrinolytic systems, plus vitamin K-dependent protein
• Production and conjugation of bile acids
• Detoxification of potential poisonous compounds
• Metabolization of alcohol
• Maintaining hormone balance
• Fetal blood production
• Synthesis of immunogenic factors
• Catabolism of complex nutrients
• Regulation of multiple processes essential for homeostasis
• Production of bile, which helps carry waste away and break down
fats in the small intestine during digestion
• Production of certain proteins for blood plasma
• Production of cholesterol and special proteins to help carry lipids through the body
• Conversion of excess glucose into glycogen for storage (glycogen can later be converted back to glucose for energy)
• Regulation of blood levels of amino acids, which form the building blocks of proteins
• Processing of hemoglobin for reuse of its iron content
• Conversion of poisonous ammonia to urea (urea is an end product of protein metabolism and is excreted in the urine)
• Clearing the blood of drugs and other poisonous substances

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The metabolic pathways of the liver for synthesis are equally complex as they are exquisitely sensitive to even the slightest environmental or genomic variable. These pathways form a myriad of interdependent functions that demand an exact interface with one another, less some potentially morbid imperfection, flaw or deficiency eventuate. Most errors in biosynthetic pathways are highly detrimental to normal existence, if not fatal.

Another crucial role of the liver is catabolism. Once the liver has broken down harmful substances, catabolic by-products are excreted into the bile or blood. Bile by-products enter the intestine and ultimately leave the body as feces. Blood by-products are filtered out by the kidneys, and leave in the form of urine.

A special feature of the liver is the ability to regenerate. The initial capacity can be exceeded by repeated, or extensive damage. If one section of the liver is damaged, another section will perform the functions of the injured area indefinitely, or until the damaged section is repaired. Unfortunately, the liver is subject to many diseases that can overwhelm its regeneration abilities, threatening a personʼs health and life.

With such a multitude of complex and essential functions, the liver is vulnerable to a plethora of prospective opportunities for serious and life threatening diseases and disorders. This is especially true in children who are either born with liver disease or acquire the disease later. The incidence has been estimated to be as high as 1 in every 2,500 live births. There are over 100 identified inborn diseases or disorders found in newborns. These include such diseases as biliary atresia, galactosemia, Wilsonʼs disease, Ryeʼs Syndrome, hemophilia, urea cycle disorders and hereditary tyrosinemia. There are over 40,000 deaths each year in the United, due to liver disease.

Liver disease varies in severity from mild infection to life-threatening liver failure. Some liver diseases, such as amebiasis and schistosomiasis, are caused by parasites. Drug use, including long-term use of some prescription medications, as well as illegal drugs, can also cause liver damage. Poisons can easily damage liver cells, and in severe cases, even cause complete liver failure, especially the poisons found in certain mushrooms. Whenever injury or disease affects the rest of the body, the liver can also be affected. Cancer, for example, can spread from the stomach, or intestines, to the liver. Diabetes, if not treated properly, can also result in damage to the liver.

Hepatitis is one of the most common liver diseases - an inflammation to the liver. Hepatitis may be caused by exposure to certain chemicals, by autoimmune diseases, or by viral or bacterial infections. Chronic hepatitis causes scarring and destruction of liver cells. Over many years, this scarring can progress to cirrhosis, a disease characterized by diminished blood flow through the liver. When this occurs, toxins are not adequately removed from the blood, the blood pressure increases in the hepatic portal vein, and substances produced by the liver, such as blood proteins, are not adequately regulated. Cirrhosis cannot be reversed, but can improve significantly with treatment that may include drug therapy or surgery to redirect the blood flow. For severe liver disease or impending liver failure, organ transplantation may be an option; although, liver transplants are complex procedures with only modest long-term success rates. However, newer techniques and drugs are improving the outcome of liver transplants, with more than half of recent transplant recipients surviving more than five years.

Sheltered by its position in the abdominal cavity, the liver filters blood from both the portal and systemic circulations. Technically, the liver is part of the gastrointestinal system and plays an important role in blood circulation. Because the liver processes all of the gastrointestinal blood through the portal vein, delivering it to the right side of the heart, it is often referred to as the “antechamber of the heart.”


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Asklepion Intervention

Understanding the vital, yet highly variable roles of the liver, presents the question of “does the milieu of integrated diseases form a logical basis for the vision of a company focused on the research, development and marketing of biopharmaceutical products for the unmet, or underserved needs, of patients with liver based diseases?” While the nature of liver based diseases is vast and overwhelming, the number of hepatologists is relatively small, and marketing access to them is very efficient. Many of the more prevalent disorders and the needs of those patients have already been addressed by large pharmaceutical companies. However, there are also conditions with substantial unmet medical needs. An example of this would be Nonalcoholic Steatohepatitis (NASH), which affects over two percent of the American population (>7,000,000), accounting for approximately ten percent of all liver disease. There are a large number of disorders that represent relatively small numbers of patients in each cohort. These groups have been neglected by the large pharmaceutical companies simply due to the high opportunity costs as compared to traditional “big Pharma” markets. Examples of these disorders include autoimmune hepatitis, neonatal jaundice, portal hypertension, and sarcoidosis.

There remains a great deal yet to be discovered, beyond perfecting the understanding of what is already known. This accentuates the presence of multiple intradisciplinary, as well as interdisciplinary, opportunities to alleviate assorted disease burden and disorders. The number and potential targets for up regulation and/or down regulation of multiple receptors, genes, and pathways, is vast. The opportunities for product development are great and commensurate to the ever increasing demands for such products.

In 2006, Asklepion Pharmaceuticals, LLC, was created as a fulfillment to these opportunities for drug research and development, regardless of the potential market size. Since our initial vision, Asklepion has entered into relationships with various universities and hospitals to develop drugs for both very large patient populations as well as for small subsets of patients.



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