Hepatitis D Virus (HDV) Co-Infection, Superinfection, Symptoms

There are five main types of hepatitis viruses that can infect the liver and cause inflammation. Some of these will cause acute inflammation and resolves spontaneously or with minimal treatment and there is no risk of chronic infection. Others may present with an acute phase but chronic infection persists for life and may lead to irreversible damage. The hepatitis virus, depending on the type, is spread through contaminated food or water or through contaminated bodily fluids like blood, semen and sometimes even saliva. The virus reaches the hepatocytes (liver cells), implants its genetic material within the host cell and causes it to replicate more virions while destroying the host cell in the process. This interaction is between the human host and virus. However, a certain type of hepatitis virus is actually dependent on the presence of another type of hepatitis virus to cause an infection.

What is hepatitis D virus?

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Hepatitis D is an infection of the liver caused by the hepatitis D virus (HDV). It is unique among the hepatitis viruses because it is an “incomplete” virus and has a single strand of RNA that is shorter than the genetic material of any known animal virus. In order to complete its life cycle, the hepatitis D virus is dependent on the presence of the hepatitis B virus (HBV). Therefore the hepatitis D virus can only infect those with an active hepatitis B infection or chronic carriers of HBV. The mode of transmission of HDV is the same as HBV and is therefore more frequently seen among IV drug users, health workers, sex workers and any person receiving a transfusion on a regular basis.

Virus Characteristics

The hepatitis D virus is a subviral particle belonging to the Deltaviridae family. It is small and has a single circular strand of RNA surrounded by a double-shelled envelope. HDV measures only 35nm in diameter and is so compact because it has the short single strand of RNA and lacks other the enzyme necessary for its replication. Host RNA polymerase is used for synthesis of new viral RNA. The outer layer of the envelope has the same proteins as the hepatitis B virus (HBsAg). The inner covering is the only protein that is produced by the virus and is referred to as the delta antigen (HDAg). The host immune activity is directed at this delta antigen and antibodies are formed against against it.

Co-infection vs Superinfection

The hepatitis D virus requires the presence of an HBV infection or at least carrier state. Therefore HBV is referred to as the helper virus. There are two important terms to describe its dependence on HBV. Co-infection is when HDV infects a person at the same time as HBV. Superinfection is when HDV infects a person who is a chronic carrier of HBV.

The difference does have some clinical importance. Co-infection causes acute hepatitis B+D . First the HBV must become established so that the HDV can then begin to replicate as it requires the HBV surface antigens (HBsAg). The ensuing hepatitis is acute and self-limiting. About 5% of these co-infection cases will progress to chronic liver disease. In superinfection, the diseases starts about 6 to 9 weeks later where there is either a severe acute hepatitis or an exacerbation of a pre-existing chronic hepatitis. About 70% to 80% will progress to chronic liver disease like cirrhosis or liver cancer.

Another type of infection that is not commonly seen occurs in liver transplant patients and is known as helper-independent latent infection. Here the transplant recipient does not have hepatitis B and is also not a chronic carrier. However HDV is detectable in the nuclei. Hepatitis B immunoglobulins suppress reactivation but once this is overcome an active HBV infection arises then the HDV is also activated. The period in-between does not cause any liver diseases, however, chronic liver disease is a risk once reactivation arises.

Antigen-Antibody Levels : Results of Blood Tests

IgM antibodies (anti-HDV) against the delta antigen (HBDAg) is detectable early in acute hepatitis. It lasts for approximately 8 weeks and will then disappear in most patients. IgG antibodies against the HBDAg persists for longer, usually throughout life.

  • Acute/ recent infection – IgM type of anti-HDV and HBcAg (hepatitis B core antigen).
  • Chronic infection – IgM and IgG anti-HDV and HbsAg (hepatitis B surface antigen).

Spread of Hepatitis D

The routes of transmission are similar to hepatitis B and includes blood and semen. Spread via saliva, as is the case with HBV, is unknown in HDV. Vertical transmission (mother to child) is also possible but uncommon. HDV is more commonly seen in IV drug users, sex workers and health workers but it is becoming less frequent with the immunization of high risk individuals. Preventing hepatitis B with the vaccine also offers protection against hepatitis D since HDV is dependent on HBV infection. Anywhere between 20% to 40% of chronic hepatitis B carriers will also have hepatitis D antibodies (anti-HDV). Contracting HDV through the use of contaminated tattoo needles, acupuncture needles and with body piercing is possible but less frequently seen these days.

Signs and Symptoms of Hepatitis D

The incubation period for HDV depends on whether it is a co-infection or superinfection as the HBV surface antigens are necessary for HDV replication. Therefore in co-infection it depends on when there is sufficient surface antigens while with superinfection it is about 6 to 9 weeks. With co-infection, acute hepatitis occurs but it is self limiting. With superinfection, a severe acute hepatitis will arise. Some HBV carriers may not even be aware of the HBV infection until the onset of hepatitis following the inoculum of HDV. However those patients with chronic hepatitis B will report an aggravation of the condition. The clinical features may include :

  • Jaundice
  • Abdominal pain
  • Nausea and vomiting
  • Dark urine
  • Lack of appetite

Other features like significant unintentional weight loss, abdominal distension, severe fatigue and weakness with enlargement of the liver and/or spleen is seen with chronic infections. As it progresses further, hepatic encephalopathy may be seen.

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