Liver: Function, failure & disease

The liver is an abdominal glandular organ in the digestive system. It is located in the right upper quadrant of the abdomen, under the diaphragm and on top of the stomach. The liver is a vital organ that supports nearly every other organ to some capacity.

The liver is the body’s second-largest organ (skin is the largest organ), according to the American Liver Foundation (ALF), weighing about 3 lbs. (1.4 kilograms). At any given moment, the liver holds about 1 pint (half a liter) of blood — about 13 percent of the body’s blood supply, according to Johns Hopkins Medicine. 

The liver is shaped like a football, or a cone, and consists of two main lobes. Each lobe has eight segments that consist of 1,000 small lobes, or lobules, according to Johns Hopkins. The lobules are connected to ducts that transport bile to the gallbladder and small intestine.

Function

“The liver has a complex role in the function of the body,” said Jordan Knowlton, an advanced registered nurse practitioner at the University of Florida Health Shands Hospital. “Detoxification, metabolism (including regulation of glycogen storage), hormone regulation, protein synthesis, digestion, and decomposition of red blood cells, to name a few.” 

In fact, more than 500 vital functions have been identified with the liver, according to Johns Hopkins, including:

• Production of bile, which helps carry away waste 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 fats through the body
• Conversion of excess glucose into glycogen for storage (glycogen can later be converted back to glucose for energy) and to balance and make glucose as needed 
• Regulation of blood levels of amino acids, which form the building blocks of proteins
• Processing of hemoglobin for use of its iron content (the liver stores iron)
• 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
• Regulating blood clotting
• Resisting infections by making immune factors and removing bacteria from the bloodstream
• Clearance of bilirubin, also from red blood cells. If there is an accumulation of bilirubin, the skin and eyes turn yellow.  

Detoxification

One of the best-known roles of the liver is as a detoxification system. It removes toxic substances from blood, such as alcohol and drugs, according to the Canadian Liver Foundation. It also breaks down hemoglobin, insulin and excessive hormones to keep hormone levels in balance. Additionally, it destroys old blood cells. 

The liver is vital for healthy metabolic function. It metabolizes carbohydrates, lipids and proteins into useful substances, such as glucose, cholesterol, phospholipids and lipoproteins that are used in various cells throughout the body, according to Colorado State University’s Department of Biomedical Sciences. The liver breaks down the unusable parts of proteins and converts them into ammonia, and eventually urea.

Liver disease

According to the Canadian Liver Foundation, there are more than 100 types of liver disease, and they are caused by a variety of factors, such as viruses, toxins, genetics, alcohol and unknown causes. The following are among the most common types of liver disease: 

• Alagille syndrome
• Alpha 1 anti-trypsin deficiency
• Autoimmune hepatitis
• Biliary atresia
• Cirrhosis
• Cystic disease of the liver
• Fatty liver disease
• Galactosemia
• Gallstones
• Gilbert’s syndrome
• Hemochromatosis
• Liver cancer
• Liver disease in pregnancy
• Neonatal hepatitis
• Primary biliary cirrhosis
• Primary sclerosing cholangitis
• Porphyria
• Reye’s syndrome
• Sarcoidosis
• Toxic hepatitis
• Type 1 glycogen storage disease
• Tyrosinemia
• Viral hepatitis A, B, C
• Wilson disease

According to the National Institutes of Health (NIH), one symptom of liver disease is jaundice — yellowish skin and eyes. Other symptoms include abdominal pain and swelling, persistent itchy skin, dark urine, pale stools, bloody or black stools, exhaustion, bruising easily, nausea and loss of appetite.

Fatty liver

There are two types of fatty liver, according to the Cleveland Clinic: that caused by excessive alcohol consumption (fatty liver) and that which is not (non-alcoholic fatty liver or non-alcoholic steatohepatitis). 

Speaking of both conditions, Knowlton said, “Some fat on the liver is normal, but when it starts to accumulate to greater than 5-10 percent, it can lead to permanent liver damage and cirrhosis.” It also increases the chance of liver failure or liver cancer. Fatty liver “can be caused by genetics, obesity, diet, hepatitis, or alcohol abuse,” said Knowlton. Other risk factors include rapid weight loss, diabetes, high cholesterol, or high trigycerides, according to the ALF. 

Some people may get fatty liver even if they don’t have any risk factors. 25-30 percent of the U.S. population suffers from fatty liver disease, according to the University of Michigan Health System. There are no medical treatments for fatty liver disease, though avoiding alcohol, eating a healthy diet, and exercising can help prevent or reverse fatty liver disease in its early stages.

Enlarged liver

According to the Mayo Clinic, an enlarged liver (or hepatomegaly) isn’t a disease itself, but a sign of an underlying serious problem, such as liver disease, cancer or congestive heart failure. 

There may be no symptoms of an enlarged liver, though if they are they are the same as the symptoms for liver disease. Normally, the liver cannot be felt unless you take a deep breath, but if it is enlarged, your doctor may be able to feel it, according to the NIH. The doctor may then do scans, MRIs, or ultrasounds of the abdomen to determine if you have an enlarged liver. Treatment will involve addressing the underlying problem.

Liver pain

Liver pain is felt in the upper right area of the abdomen, just below the ribs. Usually, it is a dull, vague pain though it can sometimes be quite severe and may cause a backache, according to the Cleveland Clinic. Sometimes people perceive it as pain in the right shoulder. It is often confused with general abdominal pain, back pain or kidney pain, according to New Health Guide. It can be hard to pinpoint the exact location or cause of such pains, so it is important to see a doctor. Doctors may do blood tests, ultrasounds or biopsies to determine the cause of pain.

Liver pain can be the result of a variety of causes. Some common causes are: ascites (fluid in the abdomen), cirrhosis, hepatitis, liver failure, enlarged liver, liver abscess, and liver tumors. 

Liver failure

Liver failure is an urgent, life-threatening medical condition. It means that the liver has lost or is losing all of its function. “Livers typically fail gradually,” said Knowlton, “but sometimes [it] can be rapid.” Early symptoms of liver failure are general, making it difficult to know that the liver is failing. Knowlton said, “Symptoms of liver failure may include nausea, appetite changes, fatigue, diarrhea, jaundice, easy bleeding.” As the condition worsens, she said symptoms might include “mental confusion and coma.”

“Typical causes of liver failure include Tylenol overdose, viruses, hepatitis B & C, cirrhosis, alcoholism, and some medications,” said Knowlton. Georgia’s Emory Healthcare stated that there are two types of liver failure: chronic and acute. Chronic liver failure is the most common type of liver failure. It is the result of malnutrition, disease and cirrhosis, and it can develop slowly over years. Acute liver failure is rarer, and it can come on suddenly. Acute liver failure is usually the result of poisoning or a drug overdose, according to the Journal of Clinical Gastroenterology.

Liver failure treatments depend on the case. Knowlton said, “Treatment options are mostly supportive (hospitalization and treatment until the liver recovers), but ultimately may require liver transplantation.”

Liver transplant

Donated livers can come from cadavers or living donors. In the case of living donors, the donor donates part of his or her liver to another person, according to the American College of Gastroenterology. The liver can regrow itself, so both people should end up with healthy, functional livers. According to the National Institute of Diabetes and Digestive and Kidney Diseases the most common reason adults get liver transplants is cirrhosis, though transplants can also be done for patients with various liver diseases or early stage liver cancer.

A liver transplant is a very serious surgery that may take up to 12 hours. According to the Mayo Clinic, there are several risks involved with liver transplants, including:

• Bile duct complications, including leaks or shrinking
• Bleeding
• Blood clots
• Failure of donated liver
• Infection
• Memory and thinking problems
• Rejection of donated liver

According to the NHS, if you have a liver transplant, you can expect to stay in the hospital for up to two weeks after the surgery, to get regular checkups for at least three months, and to take anti-rejection and other medications for the rest of your life. It will take six months to a year to feel fully healed from the surgery.

Liver transplant success depends on the individual case. Transplants from cadavers have a 72 percent success rate, meaning that 72 percent of liver transplant recipients lived for at least five years after the surgery. Transplants from living donors had a slightly higher success rate, at 78 percent, according to the Mayo Clinic.

Things that can harm the liver

While some liver diseases are genetic, others are caused by viruses or toxins, such as drugs and poisons. Some risk factors, according to the Mayo Clinic, include drug or heavy alcohol consumption, having a blood transfusion before 1992, high levels of triglycerides in the blood, diabetes, obesity and being exposed to other people’s blood and bodily fluids. This can happen from shared drug needles, unsanitary tattoo or body piercing needles, and unprotected sex.

Alcohol is big player in liver damage. It is believed that alcohol could possibly change the type of fungi living in the liver, leading to disease, according to a small study published in the Journal of Clinical Investigation. If this is true, it could lead to new treatment options. The findings suggest that “we might be able to slow the progression of alcoholic liver disease by manipulating the balance of fungal species living in a patient’s intestine,” study co-author Dr. Bernd Schnabl, an associate professor of gastroenterology at the University of California, San Diego School of Medicine, said in a statement. 

Additional resources

Read five further facts about the liver at the British Liver Trust website. Additionally, you can learn more about liver and bile duct cancer at the National Cancer Institute website. 

Bibliography

“Metabolic Functions of the Liver”. Colorado State University’s Department of Biomedical Sciences. http://www.vivo.colostate.edu/hbooks/pathphys/digestion/liver/metabolic.html

“Liver Disease”. National Library of Medicine (2021). https://medlineplus.gov/liverdiseases.html#cat5

“Acute Liver Failure”. Journal of Clinical Gastroenterology (2001). https://journals.lww.com/jcge/Abstract/2001/09000/Acute_Liver_Failure.5.aspx

“Liver Transplantation”. American College of Gastroenterology (2013).  http://patients.gi.org/topics/liver-transplantation/

“Liver  Transplanation”. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (2010). https://www.niddk.nih.gov/-/media/Files/Liver-Disease/livertransplant_508.pdf

“Intestinal fungi contribute to development of alcoholic liver disease”. Journal of Clinical Investigation (2017). https://www.jci.org/articles/view/90562