Hepatitis B: Information & hepatitis B doctors

Leading Medicine Guide Editors
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Leading Medicine Guide Editors
Hepatitis B infection is the infection of the liver with the hepatitis B virus (HBV). Around 0.5% of the German population are carriers of this virus. The hepatitis B virus is usually transmitted via infected blood, sexually or during birth. In most patients (over 90 %), the disease heals itself after an acute course. Here you will find further information as well as selected doctors and centers for hepatitis B.
ICD codes for this diseases: B16

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Article overview

Hepatitis is an inflammation of the liver.

In Germany alone, an estimated two million people suffer from chronic liver disease. Liver cirrhosis (scarring changes to the liver) is one of the four most common causes of death in adults between the ages of 30 and 50. In addition to alcohol, viral hepatitis B and C are the main causes of chronic liver disease.

In Germany, 30 to 40 % of viral hepatitis is caused by the hepatitis B virus. Around 0.5 % of the German population are carriers of the hepatitis B virus, i.e. they are infectious. Several thousand new hepatitis B infections occur in Germany every year.

According to WHO estimates, 300 to 420 million people worldwide are infected with chronic hepatitis B. Approximately one million people die each year as a result of this disease.

The liver

Weighing around 1,500 g, the liver is the largest internal organ in the human body. It is located in the right upper abdomen and is surrounded by a connective tissue capsule.

The liver is the body's central metabolic organ. One of its tasks is to break down toxins before they enter the large bloodstream. Toxins enter the body via the intestines. Food components that enter the liver via the intestine are also processed here.

Die Lage der Leber im menschlichen Körper
The liver has a number of vital functions in the human body © nerthuz | AdobeStock

In addition, the liver produces important proteins that are necessary for blood clotting and defense against infections, for example. Another important function is the production of bile, which is channelled into the duodenum via a special duct system. The bile is used to dispose of breakdown substances from red blood cells and enables the digestion of fat. Various toxins are also excreted from the body with the bile.

The liver itself has no nerve fibers that can transmit pain. However, if the liver swells or scars due to inflammatory processes, pain can be caused by tension in the connective tissue capsule.

Definition: What is viral hepatitis B?

Hepatitis B infection is the infection of the liver with the hepatitis B virus (HBV). In most patients (over 90 %), the body can cure the disease itself after an acute course. It is not uncommon for patients to not even notice that they are infected with the virus.

In less than 10 % of infected patients, however, the body's own defense system is unable to successfully fight the virus. If the disease lasts longer than six months, it is referred to as chronic hepatitis B.

The clinical course of chronic hepatitis B depends on

  • the amount of virus in the body and
  • the strength of the patient's immune defenses.

There are forms of chronic hepatitis B in which only a few viruses are produced in the body

  • only a few viruses are produced (low-replicative form of chronic hepatitis B) and
  • others in which a large number of viruses are produced (highly replicative form).

In the case of low-replicative chronic hepatitis B, there is usually no rapid progression of the disease. In most cases, patients have normal liver values. The HBs antigen can be detected in these patients, but the HBe antigen is usually not detectable in the blood.

In the case of highly-replicative chronic hepatitis B, more than 100,000 virus copies per ml of blood can be detected (this corresponds to approx. 20,000 IU/ml). In addition to the HBs antigen, the HBe antigen can also be detected. However, in many patients (approx. 50 %) with a highly replicative form of chronic hepatitis B, the HBe antigen is not detectable.

Blood tests can be used to differentiate which form of chronic hepatitis B is present in a particular patient. A doctor can differentiate between

  • the antigens and antibodies present in the blood,
  • the amount of virus in the blood (viral load),
  • the transaminases and
  • the histological examination of the liver tissue

an accurate picture of the patient's infection.

Disease mechanism in hepatitis B

In a chronic infection, new liver cells are constantly infected by the hepatitis viruses. The infected liver cells die and are replaced by new liver cells.

As a sign of inflammation, white blood cells migrate into the liver tissue. They ensure that infected and dead liver cells are destroyed and cleared away. As a rule, they are unable to eliminate the virus itself. The dead liver cells can later be replaced by connective tissue (= scar tissue).

If the liver is altered by connective tissue, this is referred to as liver fibrosis in the early stages and later as liver cirrhosis. Connective tissue can be at least partially broken down again if chronic hepatitis B is successfully treated.

Darstellung von Leberzirrhose
In liver cirrhosis, the liver slowly scars and loses its function © SciePro | AdobeStock

Infection with the hepatitis B virus

The hepatitis B virus is usually transmitted via infected blood, sexually or during childbirth. The hepatitis B virus is much more contagious than, for example, the AIDS virus (HIV) or the hepatitis C virus.

The hepatitis B virus is only transmitted from person to person.

Sexual transmission

Unlike the hepatitis C virus, sexual transmission of the hepatitis B virus is common. Patients in whom viruses can be detected in the blood should use condoms to protect their partner.

However, transmission may also occur through saliva and other bodily fluids. It is therefore important to vaccinate your sexual partner.

Transmission through blood

The hepatitis B virus can be transmitted through blood or blood products. The modern tests used today to check blood are very sensitive. The risk is therefore now very low.

However, the virus can also be transmitted via contaminated syringes or needles. Risk factors for infection with the hepatitis B virus are therefore the use of

  • drugs,
  • tattoos or
  • body piercing.

The hepatitis B virus can also be transmitted via

  • open wounds,
  • razor blades or
  • toothbrushes

is also possible.

Infection of newborns

The risk of a newborn being infected by an infected mother is greatest during or shortly after birth. The risk of virus transmission during delivery is between

  • 10 % (low-replicative chronic hepatitis B) and
  • almost 100 % (highly replicative chronic hepatitis B).

Therefore, the newborn must always receive active and passive immunoprophylaxis immediately after birth. The newborn is therefore vaccinated and given immunoglobulin at the same time.

Whether a hepatitis B infection can be transmitted through breastfeeding is still controversial. There appears to be a correlation between the probability of transmission of the virus during breastfeeding and the mother's viral load.

Consequences of hepatitis B

Cirrhosis of the liver

Patients with chronic hepatitis B have a significantly increased risk of developing liver cirrhosis in the following decades. The risk of developing liver cirrhosis depends, among other things, on the activity and duration of the disease.

Factors that can further accelerate the development of liver cirrhosis are additional chronic liver diseases, e.g.

  • with other hepatitis viruses (e.g. an additional infection with the hepatitis C virus) or
  • substances that damage the liver. This primarily includes alcohol.

Cirrhosis of the liver occurs when a large part of the liver tissue has been replaced by connective tissue. This destroys the normal structure of the liver tissue.

Blood circulation

This leads to changes in the blood circulation, which can result in high blood pressure in the portal vein. The portal vein is the vein between the intestine and the liver. A backlog of blood can lead to the formation of dilated veins (varices) in the oesophagus and stomach.

If these vessels burst, this can lead to severe gastrointestinal bleeding. The risk of bleeding is increased by the fact that the coagulation capacity of the blood is restricted by the disease. The reason for this is the reduced protein synthesis in the liver and a reduction in the number of blood platelets (thrombocytes).

The high blood pressure in the liver can also lead to the retention of body fluid in the abdominal cavity(ascites).

Toxins and metabolism

As liver cirrhosis progresses, the liver no longer functions properly. It can no longer break down some of the toxins that enter the blood from the gastrointestinal tract. As a result, they enter the body's circulation. Here they can lead to increased tiredness and poor concentration. This symptom is also known as hepatic encephalopathy, encephalon = brain.

Due to the reduced protein production, there is also a lack of production of substances that are needed for the body's defenses. The result is an increased susceptibility to infections.

Further consequential damage

Due to the backlog of bile, severe liver disease often results in yellowing of the eyes and skin (jaundice). This is often associated with itching. At the same time, the urine may become darker in color.

Gelbe Augen bei Gelbsucht
Yellow discoloration of the eyes is a symptom of a backlog of bile as a result of hepatitis B © blackday | AdobeStock

After a long course, chronic hepatitis B also increases the risk of developing liver cancer (hepatocellular carcinoma). Patients with a high viral load (HBV DNA) have a particularly high risk. In most patients, hepatocellular carcinoma develops on the basis of liver cirrhosis.

Patients with a low-replicative form of chronic hepatitis B also have an increased risk of developing hepatocellular carcinoma. Regular ultrasound and blood tests are therefore also necessary for these patients.

In some cases, chronic hepatitis B takes such a severe course that a liver transplant may be necessary.

Hepatitis D

Hepatitis D is another viral disease of the liver. It is caused by the hepatitis D virus. Only patients who also have hepatitis B are at risk of hepatitis D. This is because the hepatitis D virus requires certain proteins from the hepatitis B virus in order to multiply. Without these structures, the virus cannot multiply.

The hepatitis D virus can cause more severe liver inflammation than a chronic infection with the hepatitis B virus alone.

The hepatitis D virus is mainly found in southern countries (Mediterranean countries, South America, Africa). If you have chronic hepatitis B, you should ask your doctor how you can protect yourself against the hepatitis D virus. As a general rule, you should avoid traveling to areas with a high incidence of hepatitis D virus infections.

Symptoms of hepatitis B

The incubation period, i.e. the time between infection and the appearance of the first symptoms, is between six weeks and four months. Some patients now experience

  • flu-like symptoms,
  • joint pain and
  • fatigue.

Only some patients develop the "typical" symptoms of severe liver disease, such as

  • jaundice (icterus) with discolored stools and brown urine and upper abdominal discomfort.
  • upper abdominal discomfort.

Around two thirds of patients with acute hepatitis B experience few or no symptoms.

The symptoms of chronic hepatitis B are usually even less pronounced. Some patients experience increased tiredness or right-sided upper abdominal pain. Many patients do not notice the disease.

Diagnosis of hepatitis B

Blood tests as part of hepatitis B diagnostics

The basis for the diagnosis of hepatitis B is the examination of various antigens and antibodies. Most important is the detection of anti-HBc antibodies and the HBs antigen.

If the HBs-Ag is positive, further tests should follow to provide information about the activity of the hepatitis. These are on the one hand the HBe-Ag and anti-HBe and on the other hand the direct determination of the amount of viral DNA in the blood (viral load).

The liver values (GPT, GOT) provide limited information about the inflammatory activity of hepatitis. The activity of the disease and the connective tissue reaction in the liver can only be reliably assessed by means of a liver tissue sample.

Non-invasive procedures such as elastography allow an indirect assessment of the stage of fibrosis.

Patients with chronic hepatitis B have a higher risk of developing liver cancer. Therefore, the alpha-fetoprotein (AFP) should be determined at six-monthly intervals as a tumor marker of hepatocellular carcinoma and the liver should be examined using ultrasound.

Liver biopsy (liver puncture) and hepatitis B

A liver puncture is necessary in order to obtain important information about the degree of the disease prior to treatment. This includes, for example, the proportion of connective tissue fibers and the inflammatory activity in the liver.

During a liver puncture, a small piece of tissue is removed under local anesthesia. This sample is examined histologically under a microscope. In order to assess the success of the therapy, a further liver biopsy may be useful after treatment has been completed.

Non-invasive procedures (laboratory parameters, elastography) can predict the presence of liver cirrhosis quite reliably even without a liver biopsy.

Laboruntersuchung einer Gewebeprobe
By examining a tissue sample, doctors can gain important insights into liver function © chokniti | AdobeStock

Treatment of chronic hepatitis B

Therapy with antivirals

In recent years, numerous substances have been tested that can directly inhibit virus replication (antivirals). Treatment of chronic hepatitis B does not usually lead to complete elimination of the virus from the body. In some patients, a highly-replicative form can be permanently converted into a low-replicative form.

However, the majority of patients require long-term, sometimes permanent treatment in order to prevent the disease from progressing. It is therefore particularly important to carefully discuss the need for treatment and the treatment goals with the doctor once the diagnosis has been made.

As a rule, treatment is always necessary

  • severe liver inflammation and high liver values,
  • significant connective tissue reactions in the liver and
  • a high HBV DNA concentration (viral load) in the blood.

Viral replication and the activity of chronic hepatitis B can be inhibited with the following agents:

  • Lamivudine,
  • telbivudine,
  • entecavir,
  • adefovir and tenofovir.

These substances are grouped together as nucleoside or nucleotide analogs.

When is treatment with nucleos(t)id analogs carried out?

In principle, all patients with chronic hepatitis B can be treated with these substances. Patients who do not have sufficient long-term chances of success with interferon therapy also respond.

Patients can also be

  • for whom therapy with interferon alfa has not been successful, or
  • who cannot receive interferon alfa due to another existing underlying disease (e.g. immunodeficiency, after transplantation, HIV infection, etc.)

be treated with nucleos(t)id analogs.

Lamivudine, telbivudine, entecavir, adefovir and tenofovir are taken as tablets. The dose is:

  • Lamivudine: 100 mg per day,
  • Adefovir: 10 mg per day,
  • Entecavir: 0.5-1.0 mg per day,
  • Telbivudine: 600 mg per day,
  • Tenofovir: 245 mg per day.

Side effects of nucleos(t)id analogs

In contrast to interferon therapy, side effects are very rare with nucleos(t)id analogs.

Possible side effects are

  • Headaches,
  • fever,
  • skin rash,
  • a general feeling of illness,
  • gastrointestinal complaints,
  • insomnia,
  • cough and
  • pancreatitis in some cases.
Grippe und Müdigkeit
A general feeling of illness is one of the side effects of treatment with nucleos(t)id analogs © Justlight | AdobeStock

    Kidney function should be monitored regularly during treatment with adefovir and tenofovir.

    Compared to other preparations, resistance to the substances develops more frequently and more quickly during treatment with lamivudine.

    Fortunately

    • Lamivudine- and telbivudine-resistant hepatitis B viruses respond to adefovir or tenofovir and vice versa
    • Adefovir-resistant viruses respond to lamivudine, telbivudine and entecavir.

    Tenofovir-resistant viruses have not yet been observed clinically.

    If resistance occurs, two suitable (non-cross-resistant) drugs should always be taken together (combination therapy).

    Patients who do not respond sufficiently to the drug can be given a suitable second drug at an early stage. This avoids the occurrence of resistance.

    Therapy with (pegylated) interferon alfa

    Interferon alpha is an endogenous protein that is produced by the white blood cells, among other things. This happens in particular when the body has to defend itself against infectious agents.

    The interferon alfa used to treat chronic hepatitis is produced biotechnologically. Interferon alfa must be injected into the subcutaneous fatty tissue. Newer interferons have a longer duration of action and only need to be injected once a week (so-called pegylated interferons).

    How is therapy administered?

    Currently, the long-acting pegylated interferons are administered in a dosage of

    • 180 µg/week (peg-interferon alfa-2a) or
    • 50-100 µg/week (peg-interferon alfa-2b)

    are used. In Germany, peg-interferon alfa-2a is approved for the treatment of chronic hepatitis B.

    Treatment with peg-interferon should last 48 weeks. The response rate to peg-interferon therapy for chronic hepatitis B is 30-35% of patients. These figures apply to patients in whom the HBe antigen could be detected.

    In other patients, e.g. patients infected with a variant of the hepatitis B virus (so-called HBeAg minus mutant), the sustained response rate to peg-interferon therapy is 20%.

    The aim of the therapy is to inhibit viral replication. Highly-replicative chronic hepatitis B is thus converted into low-replicative chronic hepatitis B.

    In the ideal case (rare), the HBs antigen can no longer be detected after treatment with peg-interferon, which is equivalent to a cure.

    Side effects of pegylated interferon alfa

    The side effects of interferon alfa are common at the start of therapy and generally decrease significantly over the course of treatment.

    The most common side effects are flu-like symptoms

    • such as fever, headache, joint and muscle pain,
    • tiredness,
    • loss of appetite and weight loss.

    Occasionally, thyroid dysfunction also occurs. Some patients suffer from temporary hair loss during treatment. Mood changes and even depression can also occur.

    Blood count changes are also important, which mainly affect the white blood cells. Pegylated interferons have the same spectrum of side effects as standard interferons.

    Müdigkeit
    Fatigue is a side effect of drug treatment for hepatitis B © kite_rin | AdobeStock

    Combination therapies

    Initial studies on the combination therapy of pegylated interferons plus nucleos(t)id analogs (e.g. lamivudine) were disappointing. The long-term virological success rates could not be improved.

    The combination of two antivirals (e.g. lamivudine plus adefovir) does not have a better antiviral effect than one alone. However, it can be useful to prevent the development of resistance in patients at risk (e.g. before and after liver transplantation).

    Once resistance has developed, combination therapy is indispensable.

    Nutrition for hepatitis B

    As long as liver function is not impaired, the patient does not need to follow a special diet. If liver function is impaired, the patient should consume less protein (meat and dairy products) and salt. Your doctor should discuss this with you, possibly together with a nutrition specialist. It is important that you avoid alcohol.

    Vaccination against hepatitis B

    Vaccination against hepatitis B is possible. For some years now, it has been one of the vaccinations recommended by the Standing Committee on Vaccination (STIKO) for

    • infants,
    • small children and
    • adolescents between the ages of 11 and 15.

    The costs for these age groups are covered by the health insurance companies.

    Other groups of people who should be vaccinated against hepatitis B are

    • People with a particular risk of infection in their profession (medical and dental professions, police officers, first responders),
    • dialysis patients,
    • all patients with other chronic liver diseases (e.g. chronic hepatitis C),
    • people with close contact to patients with chronic hepatitis B and
    • Newborns of infected mothers.

    Three vaccinations are required for adequate protection. After this, over 90% of vaccinated people are reliably protected against infection.

    Further information on hepatitis B can be found on the website of Deutsche Leberhilfe e.V.

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