The liver weighs approximately 1500g and is the largest internal organ in the human body. It is located in the upper-right abdomen and is encapsulated in connective tissue.

The liver is the body's central metabolic organ. Its tasks include breaking down toxins that have entered the body through the intestines before they can reach the bloodstream. Nutrients entering the liver via the intestines are processed here. The liver produces key proteins needed for tasks such as blood clotting and warding off infection.

Another important function is the production of bile, which travels to the duodenum through a specialised system of ducts. The bile removes waste matter from the red blood cells and facilitates the digestion of fats. Various toxins are also excreted from the body via the bile.

The liver itself has no nerve fibres to transmit pain. However, pain may be caused by tension in the connective tissue enclosing the liver when the liver swells or develops scarring as a result of inflammatory processes.

Hepatitis B infection is infection of the liver with the hepatitis B virus (HBV). In most cases (>90%) the body self-heals after acute hepatitis B infection. Many people recover from infection with the virus without noticing it. However, in fewer than 10% of cases, the body's immune system is unable to deal with the virus. People whose illness persists for longer than six months are said to have chronic hepatitis B.

The clinical manifestations and outcome of chronic hepatitis B depend on the amount of the virus in the body and on the strength of the immune system. The degree of hepatitis activity can be gauged on the basis of certain viral components in the blood, the antibodies produced by the human body in response to these virus components, and other laboratory markers.

Some forms of chronic hepatitis B produce only small amounts of the virus in the body (low-replicative chronic hepatitis B). Other forms of the disease produce the virus in very large amounts (high-replicative chronic hepatitis B). Low-replicative chronic hepatitis B is not usually associated with rapid disease progression. Most people have normal results in liver function tests. HBs antigen can be identified in their blood, but HBe antigen is not usually detected.

People with high-replicative chronic hepatitis B have more than 100,000 virus copies per ml of blood (corresponding to approximately 20,000 international units [IU]/ml). HBe antigen may be detected as well as HBs antigen. However, HBe antigen is not detected in many people (approximately 50%) with high-replicative chronic hepatitis B.

The type of chronic hepatitis B in a particular patient can be identified on the basis of blood tests. The antigens and antibodies in the blood, the amount of virus in the blood (viral load), liver function tests (enzyme levels), and histology tests on liver tissue tell the doctor more about the level of hepatitis activity.

Antigens (Ag) are substances which the body identifies as foreign (e.g. virus components) and which lead to the production of antibodies (Ab).

Between six weeks and four months after infection with hepatitis B virus (the incubation period), some people experience flu-like symptoms, joint aches and fatigue. Not all patients develop the ‘typical’ symptoms of severe liver disease such as jaundice with discoloured stools and brown urine, and upper abdominal pain. Around two-thirds of people with acute hepatitis B experience few symptoms, if any.

The symptoms of chronic hepatitis B are usually even less apparent. Some people feel very tired or experience pain in the upper-right side of the abdomen, and many do not notice symptoms at all.

In people with chronic infection, the hepatitis virus keeps infecting more and more liver cells. The infected liver cells degenerate and are replaced by new liver cells. White blood cells migrate into the liver tissue as a sign of inflammation. The white blood cells ensure that infected and dead liver cells are destroyed and cleared away, but are usually powerless to remove the virus itself. The dead liver cells may later be replaced by connective tissue (scar tissue). When connective tissue starts forming in the liver, the early stage in the process is called hepatic fibrosis and the late stage is called cirrhosis. Connective tissue can be broken down, at least in part, if chronic hepatitis B is successfully treated.

People with chronic hepatitis B have a significantly higher risk of developing cirrhosis in subsequent decades. The risk of developing cirrhosis depends, among other things, on disease activity and disease duration. Factors which may accelerate the development of cirrhosis include the presence of other chronic liver disease, such as infection with other hepatitis viruses (such as co-infection with hepatitis C virus) and exposure to substances that damage the liver. Alcohol is the key cause of this additional damage.

Cirrhosis is defined as a state in which a large part of the liver tissue has been replaced by connective (scar) tissue. This destroys the normal liver tissue structure and affects the blood supply, causing high blood pressure in the portal vein (the vein between the intestine and liver). Backflow of blood may cause dilated veins (varices) to develop in the oesophagus (food tube) and stomach. If these veins burst, severe gastrointestinal bleeding may occur. The risk of bleeding is increased because the blood's ability to clot is impaired by the reduced synthesis of protein in the liver and a reduction in the number of blood platelets.

Accumulation of body fluids (ascites) in the abdominal cavity may occur. One reason for this is the high blood pressure to the liver.

If cirrhosis is present, the liver may be unable to break down some of the toxins entering the blood from the gastrointestinal tract, allowing these toxins to enter the main circulation. These toxins may cause increased fatigue and poor concentration (hepatic encephalopathy [encephalon = brain]).

Reduced protein production in the cirrhotic liver impairs blood coagulation and results in an undersupply of substances needed by the immune system. As a result, the patient is more prone to infections.

Retention of bile in people with severe liver disease commonly causes yellowness of the eyes and skin (jaundice). This may be accompanied by itching. Dark urine may be produced. People with a long history of chronic hepatitis B are also at greater risk of developing liver cancer (hepatocellular carcinoma). The risk seems to be greatest for people with a high viral load (HBV DNA). In most cases the hepatocellular carcinoma is secondary to cirrhosis, but there are reports of liver cancer occurring in people with chronic hepatitis B who had no history of cirrhosis. People with low-replicative chronic hepatitis B (HBs antigen carriers) are also at greater risk of developing liver cancer. Therefore, these patients also require regular ultrasound scans and blood tests for monitoring purposes. In some patients, chronic hepatitis B is severe enough to warrant a liver transplant.

Hepatitis D

Hepatitis D is another viral disease of the liver. It is triggered by the hepatitis D virus. Hepatitis D can only occur in people who also have hepatitis B. This is because the hepatitis D virus needs certain hepatitis B viral proteins in order to replicate. The virus cannot reproduce without these structures.

It is possible to become infected with hepatitis D virus and hepatitis B virus simultaneously. Transmission of the virus is also possible in people who already have chronic hepatitis B. Infection with the hepatitis D virus may cause a more severe inflammation of the liver than chronic infection with hepatitis B virus alone.

Hepatitis D occurs in particular in southern countries (Mediterranean countries, South America, Africa). If you have chronic hepatitis B, you should ask your doctor how best to protect yourself against hepatitis D.

HIV

Co-infection with HIV^1,2,3,4,5,6 increases the risk that a person who is exposed to hepatitis B infection will go on to develop a chronic hepatitis B infection. It also accelerates liver disease progression and increases the risk that a co-infected person will develop cirrhosis or hepatocellular carcinoma (liver cancer). There is conflicting evidence about the impact of hepatitis B on the progression of HIV disease.

Around 9% of people with HIV in a very large study in Europe were co-infected with hepatitis B.

Treatment of hepatitis B in people with HIV infection differs from treatment for hepatitis B alone. See Treatment of chronic hepatitis B: Treatment of hepatitis B and HIV co-infection for further information.