The liver is the largest solid organ in the human body and is essential for life. As blood circulates through the liver, it performs a number of functions that are critical to sustaining life. These include metabolizing nutrients transported from the intestines, removing waste products from our body, filtering toxic substances and drugs from our blood, helping to maintain levels of blood sugar, fat, and hormones in our circulatory system, as well as participating in our immune defence against infection.

About 60 per cent of the liver is made up of liver cells called hepatocytes, which metabolize nutrients and detoxify the blood by removing harmful substances. Liver is constantly renewing itself under normal conditions, much like our blood and our bones do. Other cells within the liver include bile duct cells that transport bile necessary for absorption of fat and minerals as well as toxic products that are eliminated in the intestine. The third major cell population is macrophages and endothelial cells (reticuloendothelial cells) that contribute to the host immune system.

The liver is a very hardy organ that can withstand a great deal of abuse. Liver failure means that there is irreversible damage to the structure and function of the liver such that its effectiveness in maintaining so many of the body's essential functions is diminished beyond repair. 

Liver failure is increasing dramatically and some estimate it will triple in the next 20 years. Currently, the most common cause of liver failure is viral hepatitis - estimates are that the incidence of hepatitis C virus infection (HCV) will continue to rise over the next 10-20 years. However, a "lifestyle of excess" that is characterized by obesity and high triglycerides stresses the liver, such that the condition known as fatty liver is now emerging as a common cause of liver failure. Furthermore, deaths from alcoholic liver disease have doubled in the last 10 years , related to the eight-fold increase in young people diagnosed with alcoholic liver disease due to binge drinking.

Symptoms, causes and treatment

Liver is designed to regenerate itself as a response to regular wear-and-tear and injury. Liver failure occurs when this process is inhibited or overwhelmed and shuts down. This can be the result of both an acute trauma to the liver or the evolution of chronic liver failure over time.

There are many different kinds of liver disease - what they have in common is that they affect the structure and function of the liver. Liver disease can be caused by viruses, drugs including alcohol, genetic defects and exposure to toxic chemicals. Some common symptoms and signs associated with liver disease include nausea, vomiting, reduced appetite, jaundice, low-grade fever, abdominal pain and fatigue.

Liver disease is often diagnosed by investigating liver enzymes a marker of heaptocyte death, levels of bilirubin or disturbances in blood clotting. Liver failure can be a complication of other diseases including diabetes mellitus, heart failure and kidney failure and alcoholism. End-stage liver disease (ESLD) indicates that it is only a matter of time before the liver fails.

Some common causes of Liver Disease 

Alcohol abuse is the leading cause of liver disease in the world. Over a period of time alcohol abuse can induce permanent changes in the liver, sometimes leading to cirrhosis of the liver, which is characterized by scar tissue or fibrosis and inflammation in a significant portion of the liver. While this damage is permanent, the liver is a large organ, and other portions may remain unaffected. However, as the disease progresses, more and more of the liver becomes scarred, the capacity for regeneration in the healthy portion diminishes, and liver failure results.

Hepatitisis inflammation of the liver, most commonly caused viral infection or ingestion of toxic drugs. Hepatitis A is a virus found in contaminated food or water that infects the liver. The liver usually recovers but occasionally hepatitis A virus infection is fatal. Hepatitis B is a virus transmitted through blood and bodily fluids from mother to baby, by sexual contact and drug use. Today the incidence of new cases of HBV disease is falling due to successful vaccination programs worldwide.

Hepatitis C is a serious and incurable liver disease that is becoming more common. Caused by the HCV virus that is most often transmitted by blood, HCV infection leads to chronic inflammation of the liver and cirrhosis. It is transmitted to others, often through blood or drug use (needle-sharing). It can develop without symptoms and progress to a chronic stage before someone even knows they are a carrier.

Heavy metals, such as lead or copper, and chemicals found in pollution, fabrics, home insulation, pesticides, to name just a few sources, may also affect the liver and lead to liver failure over time.

While the liver can tolerate and recover from a certain amount of abuse, there are often no warning signs that it is failing until it is too late. Once the line is crossed from chronic liver disease to end-stage liver disease or liver failure, the options become stark. There is no "liver dialysis" that can rehabilitate liver function in the way that kidney failure is treated.

Role of Stem Cells in Liver Failure

Bone marrow is one of the sources of mesenchymal stem cells (MSCs), which are also found in bone, muscle, cartilage and fibrous tissue. They have the potential to become a variety of different cells, depending on what is needed.  Other sources for MSCs include cord blood, placental tissue and fatal liver tissue, which contain stem cells that are multi-potent and proliferate easily. In addition, stem cells are more pliable than we first believed if they are removed from their niche and put to work in other organs. In the case of liver disease, this means an MSC might be coaxed to generate hepatocytes.  It appears that MSCs may play a role in inhibiting this destructive process.

Researchers are on their way to developing an artificial liver that can replace the need for solid organ transplantation. As a first step, they have been able to speed up the proliferation of umbilical cord stem cells using a bioreactor, which produces adequate quantities for therapeutic application. Then, by adding various hormones and chemicals, these stem cells differentiate into liver cells. An important result of this research is that this tissue, which researchers call "mini-livers," can be used to test the safety and effectiveness of new drugs. Mini-livers can also cut down on the number of animal experiments. Eventually, they might be able to be transplanted. It is most likely that this technology will be used for bridge therapy, i.e. to temporarily alleviate liver distress.