From the Guidelines
The liver is a vital organ responsible for over 500 functions in the human body, including processing nutrients, removing toxins, producing proteins, and metabolizing medications, as highlighted in recent studies 1.
Liver Function and Physiology
The liver is located in the right upper abdomen and has a unique dual blood supply, with the hepatic portal vein delivering nutrient-rich blood from the digestive organs and the hepatic artery providing oxygen-rich blood. Hepatocytes, the main liver cells, perform most metabolic functions, including:
- Carbohydrate metabolism, storing glucose as glycogen and releasing it when needed
- Protein synthesis
- Fat metabolism
- Detoxification through the cytochrome P450 enzyme system The liver also produces bile, stored in the gallbladder, which aids in fat digestion and absorption, and stores vitamins A, D, E, K, and B12, and minerals like iron and copper.
Liver Health and Maintenance
Maintaining liver health is crucial, and this can be achieved by:
- Limiting alcohol consumption, as excessive alcohol consumption can lead to alcoholic liver disease, as discussed in 2
- Maintaining a healthy weight, as excess visceral adiposity is related to liver fat content, as shown in 3
- Avoiding unnecessary medications
- Getting vaccinated against hepatitis Liver function can be assessed through blood tests measuring enzymes like ALT, AST, and bilirubin levels.
Regenerative Capacity and Transplantation
The liver has remarkable regenerative capacity, able to regrow even after significant damage or surgical removal of portions. This regenerative ability allows for liver transplantation, where only part of a donor liver is needed, as mentioned in 1.
From the FDA Drug Label
After absorption, ursodiol enters the portal vein and undergoes efficient extraction from portal blood by the liver (i.e., there is a large “first-pass” effect) where it is conjugated with either glycine or taurine and is then secreted into the hepatic bile ducts. The sites of the drug’s therapeutic actions are in the liver, bile, and gut lumen. Beyond conjugation, ursodiol is not altered or catabolized appreciably by the liver or intestinal mucosa Reabsorbed free ursodiol is reconjugated by the liver Eighty percent of lithocholic acid formed in the small bowel is excreted in the feces, but the 20% that is absorbed is sulfated at the 3-hydroxyl group in the liver to relatively insoluble lithocholyl conjugates which are excreted into bile and lost in feces. Absorbed 7-keto-lithocholic acid is stereospecifically reduced in the liver to chenodiol Man has the capacity to sulfate lithocholic acid Although liver injury has not been associated with ursodiol therapy, a reduced capacity to sulfate may exist in some individuals, but such a deficiency has not yet been clearly demonstrated. Ursodiol suppresses hepatic synthesis and secretion of cholesterol, and also inhibits intestinal absorption of cholesterol
The liver plays a crucial role in the conjugation, metabolism, and secretion of bile acids. It efficiently extracts ursodiol from portal blood, conjugates it with glycine or taurine, and secretes it into the hepatic bile ducts. The liver also reconjugates reabsorbed free ursodiol, sulfates lithocholic acid, and reduces 7-keto-lithocholic acid to chenodiol. Additionally, the liver is involved in the suppression of hepatic synthesis and secretion of cholesterol. These processes highlight the liver's importance in the enthohepatic circulation of bile acids and the regulation of cholesterol levels 4.
- Key functions of the liver: + Conjugation of bile acids + Metabolism of bile acids + Secretion of bile acids into the hepatic bile ducts + Reconjugation of reabsorbed free ursodiol + Sulfation of lithocholic acid + Reduction of 7-keto-lithocholic acid to chenodiol + Suppression of hepatic synthesis and secretion of cholesterol
From the Research
Liver Functions
The liver is a vital organ that performs many essential biological functions, including:
- Detoxification of xenobiotics (drugs) and blood before access to the brain 5, 6
- Macronutrient metabolism, such as glycogen storage and decomposition of red blood cells 7, 6
- Plasma protein synthesis, hormone production, and regulation of blood volume 7, 6
- Immune system support, endocrine control of growth signaling pathways, and lipid and cholesterol homeostasis 6
- Breakdown of xenobiotic compounds, including many current drugs 5, 6
Liver Cell Biology
The liver is composed of various cell types, with hepatocytes being the predominant liver cells, comprising more than 70% of the total liver mass in human adults 8. Hepatocytes are the basic metabolic cells and possess a remarkably well-developed and complex membrane trafficking machinery 9. Mitochondria are intracellular organelles that play a major role in oxidative metabolism and sustaining liver cell energy needs 8.
Liver Physiology
The liver's capacities to store glucose in the form of glycogen, with feeding, and assemble glucose via the gluconeogenic pathway, in response to fasting, are critical 6. The liver also oxidizes lipids, but can also package excess lipid for secretion to and storage in other tissues, such as adipose 6. Additionally, the liver is a major handler of protein and amino acid metabolism, responsible for the majority of proteins secreted in the blood and the processing of amino acids for energy 6.
Liver Diseases
Any disruption in normal liver function can lead to the development of more severe liver disorders, such as steatosis, non-alcoholic fatty liver disease (NAFLD), and alcohol-associated liver disease (ALD) 8. Liver failure from any number of sources (e.g., viral infection, overnutrition, or oncologic burden) is a global health problem 6.