Global Alert and Response (GAR)

Hepatitis D

Hepatitis Delta - an introduction

- What?
- How?
- Who?
- Where?
- When?
- Why?

Hepatitis is a general term meaning inflammation of the liver and can be caused by a variety of different viruses such as hepatitis A, B, C, D and E. Since the development of jaundice is a characteristic feature of liver disease, a correct diagnosis can only be made by testing patients' sera for the presence of specific antigens and anti-viral antibodies.

In 1977, a previously unrecognized nuclear antigen was detected in hepatocytes of patients with chronic hepatitis B. The antigen resembled hepatitis B core antigen (HBcAg) in its subcellular localization. Its presence was always associated with hepatitis B virus (HBV) infection, but it rarely coexisted with HBcAg. It was termed "delta antigen". Patients with delta antigen develop anti-delta antibodies.14, 21, 22

In 1980, the delta antigen was recognized to be the component of a novel virus that was defective and required coinfection with HBV for its replication. The hepatitis delta virus (HDV) was shown to rely on HBV for transmission because it used the hepatitis B surface antigen (HBsAg) as its own virion coat.14, 21, 25

The viruslike delta agent was subsequently shown to be associated with the most severe forms of acute and chronic hepatitis in many HBsAg-positive patients. The disease it caused was designated delta or type D hepatitis.

What causes the disease?
Hepatitis D or delta hepatitis is caused by the hepatitis delta virus (HDV), a defective RNA virus. HDV requires the help of a hepadnavirus like hepatitis B virus (HBV) for its own replication.

How is HDV spread?
HDV is transmitted percutaneously or sexually through contact with infected blood or blood products.

Blood is potentially infectious during all phases of active hepatitis D infection. Peak infectivity probably occurs just before the onset of acute disease.

Who is at risk for infection?
Chronic HBV carriers are at risk for infection with HDV.

Individuals who are not infected with HBV, and have not been immunized against HBV, are at risk of infection with HBV with simultaneous or subsequent infection with HDV.

Since HDV absolutely requires the support of a hepadnavirus for its own replication, inoculation with HDV in the absence of HBV will not cause hepatitis D. Alone, the viral genome indeed replicates in a helper-independent manner, but virus particles are not released.

Where is HDV a problem globally?
The hepatitis delta virus is present worldwide and in all age groups.14, 21

Its distribution parallels that of HBV infection, although with different prevalence rates (highest in parts of Russia, Romania, Southern Italy and the Mediterranean countries, Africa and South America). In some HBV-prevalent countries such as China, HDV infection is disproportionately low.14

The natural reservoir is man, but HDV can be experimentally transmitted to chimpanzees and woodchucks that are infected with HBV and woodchuck hepatitis virus, respectively.19, 21, 24

When is a HDV infection life-threatening?
HDV infection of chronically infected HBV-carriers may lead to fulminant acute hepatitis or severe chronic active hepatitis, often progressing to cirrhosis.

Chronic hepatitis D may also lead to the development of hepatocellular carcinoma.11

Why is there no treatment for the disease?
Hepatitis D is a viral disease, and as such, antibiotics are of no value in the treatment of the infection.

There is no hyperimmune D globulin available for pre- or postexposure prophylaxis.

Disease conditions may occasionally improve with administration of a-interferon.15, 21, 25

Since no effective antiviral therapy is currently available for treatment of type D hepatitis, liver transplantation may be considered for cases of fulminant acute and end-stage chronic hepatitis D.