Work in progress - intended as replacement for Liver

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The liver is the largest organ in the body, weighing 1 - 1.5 kg. Its shape is determined by the cavity available in the upper right part of the abdomen, between the diaphragm and the rib margin. This gives a tapered appearance, much wider at the right of the body than the left.

The liver makes and breaks down various substances, stores nutrients absorbed from the intestines, and detoxifies the blood. There are many causes of liver disease:

• Alcohol poisoning - the most common cause of liver disease

• Viral hepatitis, notably hepatitis B and C¹ and the glandular fever virus EBV²)

• Autoimmune diseases, in which the immune system attacks the body's own tissues

• Poisons and drugs, including paracetamol, and some antibiotics and arthritis drugs.

• Inherited disorders, such as haemochromoatosis and Wilson's disease, in which an excess of iron or copper, respectively, leads to damage of the liver.

• Blockage of the biliary system³ leads to liver problems and jaundice.

The Liver's Normal Function

The liver receives the blood from the gut after a meal and turns sugar (glucose) into the storage molecule glycogen⁴. This is turned back into glucose when required, allowing the body to keep blood glucose levels stable. The liver also makes:

• Proteins - mostly blood proteins - such as those involved in clotting - and hormones.

• Bile acids - essential for digesting fats and absorbing vitamins from food.

Another role of the liver is in detoxification. Water-soluble toxins and waste products can be eliminated via the kidneys in the urine, but non-water soluble toxins need to be chemically modified by the liver to allow this process to occur. The liver has many enzymes to tackle both waste products of the body and chemicals not produced by the body.

The Diseased Liver

The initial response of the liver to disease is inflammation and fatty change - a process in which the tissues of the liver start to fill with fat⁵. Normally, the liver can regenerate to repair damage. Prolonged or severe inflammation, however, leads to scarring of the liver known as 'cirrhosis', which is permanent.

The most obvious sign of liver disease is jaundice. In the normal liver, haemoglobin from old red blood cells is broken down into coloured molecules that are used to produce bile ('bile pigments'). If the liver is not functioning, this process is disturbed, leading to accumulation of bile pigments and a yellowing of the skin and whites of the eyes (sclera). Other symptoms include itching, nausea and pain in the right upper area of the abdomen.

The complications of cirrhosis include:

• Lack of albumin - the blood protein albumin is made in the liver. Its role is to transport many important substances, such as fatty acids and hormones, around the body. Albumen is also critical in ensuring that the osmotic pressure of blood⁶ remains constant. If the amount of albumin in blood decreases, fluid leaks out of the vessels, leading to swelling, notably in the legs and abdomen.

• Lack of clotting factors, leading to easy bruising and internal bleeding

• Impaired mental state from low blood sugar and toxins normally removed by the liver.

Death is usually from infection from a suppressed immune system, or from vomiting blood from abnormal vessels in the oesophagus (varices). The only treatment currently available for liver failure is transplantation.

Diagnosis

Liver disease is often first detected because of abnormal results after blood tests called liver function tests (LFTs), although they are not actually a measure of liver function. Abnormal albumin and blood clotting tests also demonstrate abnormal liver function. The pattern of the abnormalities of LFTs points to whether the problem is in the liver the liver itself, in the biliary system, or the result of haemolytic anaemia, which can lead to jaundice. Other diagnostic techniques include:

• Viral hepatitis and autoimmune liver diseases can be diagnosed by the presence of particular antibodies in the blood.

• Haemachromatosis - a hereditary condition involving iron overload - can be diagnosed by detecting increased iron levels.

• Increased copper levels may be a sign of Wilson's disease.

• An ultrasound scan can show blockage of the bile duct, fatty liver, cirrhosis and liver tumours

Some of these techniques may involve a small sample (a biopsy) of the liver being removed. A liver biopsy may be necessary to examine the liver under the microscope, stain for iron or copper, or to assess viral loads.

Treatment

The main aim of treatment of liver disease is to prevent cirrhosis. Obviously alcohol consumption must stop. Hepatitides B and C can be treated with antiviral drugs. Where the patient's immune system is attacking the liver powerful suppressants of the immune system are given. N-Acetylcysteine is given to prevent damage from paracetamol overdoses. Iron or copper overload can be treated with chelating agents that help the body to eliminate the excess heavy metals.