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Hepatitis D only occurs together with hepatitis B. An infection with hepatitis B and D is usually more fulminant.

Definition: Hepatitis D is an inflammation of the liver caused by the hepatitis D virus (HDV). The virus belongs to the naked RNA viruses and was formerly also called delta virus. The infection only occurs in conjunction with a hepatitis B infection.

Epidemiology

More than 10 million people worldwide are infected with HDV. In southern Italy, central Africa and the Middle East, HDV occurs much more frequently. There, the HDV infection rate among HBsAg carriers is up to 90% (people who have had or are going through an HBV infection are mostly HBsAg carriers).

Causes

Viral hepatitis D is caused by the hepatitis D virus, which belongs to the hepadnavirus family (Hepadnaviridae). Three different genotypes of the virus are known:

  • Type I is primarily found in the western world, Taiwan and Lebanon
  • Type II is found in East Asia and type III in South America. An infection with hepatitis D is always preceded either by an infection with hepatitis B virus (HBV) or by a simultaneous infection, as HDV can only multiply if liver cells are also infected with HBV.

Pathogenesis

similar to HBV, HDV can be transmitted via three different routes of infection:

  • sexually
  • parenterally
  • perinatally.

It is often transmitted sexually. however, it can also be transmitted parenterally via the bloodstream through contaminated syringes, blood and blood products. Like HBV, there is also a risk of transmitting HDV from the mother to the newborn during birth, perinatally.

The incubation period of HDV-HBV co-infections is between three and seven weeks, but can also last up to six months.

After infection, the HB viruses penetrate the liver cells, the hepatocytes. There, their RNA is transported into the cell nucleus. In order to replicate, the HD virus needs the HBV. The exact mechanism behind replication and infection with HDV is not yet known. In contrast to HBV, however, HDV is itself cytotoxic and only causes damage to the liver cells themselves. A superinfection of HBV and HDV therefore causes severe lesions in the liver.

A distinction is made between a superinfection with HBV and HDV and a simultaneous infection or co-infection of an HBsAg carrier with HDV. HBV+HDV superinfection is the more common form.

The superinfection usually occurs when the HBV infection changes from a replicative to a non-replicative form, the HBe-Ag is lost and anti-HBe occurs. The simultaneous infection of HBV and HDV is rarer. It is usually characterized by a two-stage increase in transaminases: first due to the HBV infection and then a second time due to the HDV infection.

Symptoms:

The symptoms are initially unspecific with a feeling of illness, loss of appetite and pressure in the right upper abdomen. In the course of the disease, jaundice (icterus) develops. Dark urine and pale stools are also among the symptoms that occur. In general, the same symptoms can occur as with a simple HBV infection. However, superinfections usually cause more severe acute symptoms and have a significantly higher risk of a fulminant course of five to 20%.

Diagnostics

The diagnosis begins with a medical history. As with other viral hepatitis, the entire possible incubation period of several months should be queried retrospectively. In addition, the patient's travel history and risk profile should be obtained.

Laboratory

If an HDV infection is suspected, HBV laboratory diagnostics are carried out first. If HBsAg, HBV DNA or both titres in the serum are positive, the HDV RNA and anti-HDV IgM should be determined using ELISA. If an HBsAg carrier is superinfected with HDV, anti-HDV-IgM and HDV-RNA are positive, anti-Hbc-IgM is negative and HBsAg is persistently positive. In the case of simultaneous infection with HBV and HDV, anti-HDV IgM and HDV RNA are also positive. In contrast to superinfection, however, anti-Hbc-IgM is also positive and HBsAg is initially positive. In addition, liver enzymes such as GOT and GPT as well as cholestasis parameters with AP and gamma-GT are determined in order to evaluate the condition of the liver.

Apparative diagnostics

If a superinfection has been confirmed by the laboratory, a liver biopsy can be performed to detect HBV and HDV immunohistochemically in the tissue and to get an impression of the current condition of the liver. However, a biopsy is not absolutely necessary. A non-invasive method for assessing the tissue structure of the liver is liver elastography (fibroscan), which is carried out sonographically at Vivomed.

Therapy

The treatment of a co-infection of hepatitis B (HBV) and hepatitis D (HDV) requires a comprehensive approach, as the two viruses interact closely. The therapeutic goals are aimed at suppressing viral replication, reducing liver inflammation and preventing the progression of liver disease. Here are some aspects of treatment:

  • Antiviral therapy for hepatitis B (HBV):
  • In the case of co-infection, treatment of hepatitis B is the main focus, as the HDV requires the HBV to replicate. Antiviral drugs such as entecavir, tenofovir or peginterferon can be used against HBV.

Interferon treatment:

  • Peginterferon alfa-2a or alfa-2b can be used to treat both hepatitis B and hepatitis D in some cases. It has an antiviral and immunomodulatory effect.

Hepatitis D-specific therapy:

  • Unfortunately, to date there are no specific antiviral drugs that directly target hepatitis D. Some experimental approaches and clinical trials are underway, but there is no standardized therapy yet.

Combination treatment:

  • In some cases, a combination of antiviral drugs and interferon may be considered. However, this may vary from case to case and the benefits should be carefully weighed against possible side effects.

Regular monitoring:

  • Regular monitoring of viral load, liver function tests and other relevant parameters is crucial to assess the course of the infection and adjust therapy accordingly.

Liver transplantation:

  • In advanced cases, especially those with severe cirrhosis or liver failure, liver transplantation may be considered.

It is important to note that the treatment of co-infection of hepatitis B and D is complex and depends on many factors, including the stage of liver disease, viral load and individual patient characteristics. The decision on the best therapy should be made by an experienced hepatologist or infectious disease specialist.

Prognosis

70 to 90% of HDV cases have a severe chronic course. The risk of liver cirrhosis is significantly higher than with hepatitis B, as is the mortality rate.

As with hepatitis B, there is also an increased risk of hepatocellular carcinomas such as hepatocellular carcinoma (HCC), follow-up checks are necessary at regular intervals. Depending on the stage of the disease, these can be carried out every six months to once a year.

Prophylaxis

The hepatitis D virus can only multiply in the liver if there is a concurrent HBV infection or the patient is an HBsAg carrier. There is no vaccination against HDV. However, an HBV vaccination helps to reduce the risk of HDV infection, as this removes the basis for HDV infection.

In addition to vaccination, people at risk such as HBsAg carriers and HBV-infected persons should take precautions and general hygiene measures. Contact with potentially contaminated body fluids should be avoided. A condom should also be used during sexual intercourse to minimize the risk of sexual infection.