Hepatitis B

Disease course and symptoms

The liver

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.

Glossary

ascites

An accumulation of fluid in the abdomen; may be caused by liver damage, especially cirrhosis. 

carcinoma

A malignant tumour that may spread throughout the body.

chronic infection

When somebody has had an infection for at least six months. See also ‘acute infection’.

cirrhosis

Scarring of the liver – the structure of the liver is altered. See also ‘fibrosis’, which is moderate scarring. See also ‘compensated cirrhosis’ and ‘decompensated cirrhosis’.

DNA

Deoxyribonucleic acid, the material in the nucleus of a cell where genetic information is stored. In hepatitis B, DNA (viral load) testing is used to help predict treatment outcome and to monitor response to treatment.

encephalopathy

A disease or infection affecting the brain.

fibrosis

Scarring of the liver – the development of hard, fibrous tissue. See also ‘cirrhosis’, which is more severe scarring.

hepatic

To do with the liver.

histology

Examining a sample of cells under a microscope to determine if they are normal or if there is evidence of infections or tumours.

oesophagus

The tube leading from the throat to the stomach.

stage

The stage of hepatitis infection refers to the amount of liver scarring (fibrosis) detected by biopsy. Usually measured on scales of 0 to 4, or 0 to 6 (higher numbers indicated more severe inflammation). 

varices

Stretched veins which may burst and cause severe bleeding; a complication of cirrhosis.

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.

Viral hepatitis B

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.

Important tests for hepatitis B

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

HBs antigen

Virus component in the virus envelope; a sign of acute or chronic hepatitis B.

HBe antigen

Virus component detected in the blood. Indirect evidence of virus multiplication (replication).

HBc antigen

An element of the virus capsule. May be detected in the liver but not in the blood.

Antibodies (anti-HBs, anti-HBe, anti-HBc)

Produced by the body’s immune system to remove the virus from the body.

HBV DNA

Genetic material from the hepatitis B virus (deoxyribonucleic acid).

Transaminases

Liver enzymes (ALT, AST) indicating increased inflammatory activity in the liver.

Histology

Microscopic examination of tissue (e.g. from the liver).

Symptoms of hepatitis B

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.

Mechanism of disease

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.

Complications of hepatitis B

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 B and co-infections

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 HIV1,2,3,4,5,6 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.

This information is adapted from Hepatitis B: Risks, prevention and treatment by Prof. Stefan Zeuzem, published by the European Liver Patients Association, 2007.

References

  1. Konopnicki D et al. Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in EuroSIDA. AIDS 19: 593-601, 2005
  2. Gilson RJC et al. Interactions between HIV and hepatitis B virus in homosexual men: effects on the natural history of infection. AIDS 11: 597-606, 1997
  3. Hadler SC et al. Outcome of hepatitis B virus infection in homosexual men and its relation to prior human immunodeficiency virus infection. J Infect Dis 163: 454-459, 1991
  4. Sinicco A et al. Coinfection and superinfection of hepatitis B virus in patients infected with human immunodeficiency virus: no evidence of faster progression to AIDS. Scan J Infect Dis 29: 111-115, 1997
  5. Thio CL et al. Liver disease mortality in HIV-HBV co-infected persons. Ninth Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 656, 2002
  6. Nikolopoulos GK et al. Impact of hepatitis B virus infection on the progression of AIDS and mortality in HIV-infected individuals: a cohort study and meta-analysis. Clin Infect Dis 48(12):1763-71, 2009