Management of Chronic Viral Hepatitis (PDF)

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During hepatitis delta virus replication, the viral genome undergoes a specific nucleotide conversion that changes a uridine to a cytosine at position 1015. This conversion changes the termination codon of the small hepatitis delta antigen and allows RNA translation to continue and so produce the large hepatitis delta antigen. Hence, during replication, the virus changes its genome to allow the production of the inhibitory form of hepatitis delta antigen and then regulates its own replication.

What controls the switch from the small to the large form of hepatitis delta antigen is unclear. Once the hepatitis delta virus RNA has duplicated itself, the new RNA is bound to the hepatitis delta antigen and then packaged into viral particles that are surrounded by the envelope protein of the hepatitis B virus. The virus is then released from the cell using unknown exit pathways.

Natural history of hepatitis delta virus infection

Infection with the hepatitis delta virus is unusual and is common in only a few geographical areas, chie.y the Mediterranean area and South America. The virus can infect only those patients who are co-infected with hepatitis B virus, and two patterns of infection occur:

• co-infection, where both viruses are acquired together; and
• superinfection, where a person who already has chronic hepatitis B virus
   infection acquires hepatitis delta virus.

In co-infection a severe, acute hepatitis develops that may lead to liver failure requiring transplantation. If the patient survives the initial infection, both viruses are usually eliminated and no further therapy is required. Chronic, persistent infection develops in less than 10% of these patients. Superinfection with hepatitis delta virus also causes an acute hepatitis and, again, acute liver failure may develop, although this is less common. In contrast to coinfection, in which chronic infection is rare, most patients who are superinfected with hepatitis delta virus go on to develop persistent infection (chronic hepatitis delta). In chronic hepatitis delta virus infection, both hepatitis B virus and hepatitis delta virus persist in the liver.

The natural history of this infection is variable and differs in different geographical regions. In Italy and most other countries chronic hepatitis delta virus infection usually causes an aggressive hepatitis that progresses to cirrhosis within a relatively few years. However, on the Mediterranean island of Rhodes, hepatitis delta virus infection is common and usually leads to a mild disease that progresses very slowly. In South America, outbreaks of infection occur in which large numbers of people are infected. It is not clear whether these differences in transmission and outcome are due to different viral species or whether they are due to genetic differences in the host population.