Hepatitis D: clinical features and epidemiology

Hepatitis D, HDV is a subviral satellite that is not classified in a viral family. Dr. Mario Rizzeto identified in 1977 a nuclear antigen that was subsequently established to derive form what was named Hepatitis Delta Virus ()This is the only virus under the genus deltavirus (Hepatitis D Virus, 2005). The history of this interesting unique satellite small virus is short and therefore researches are still searching for possible new genotypes and prevention and treatment methods.

The new satellite virus was established to depend entirely on the Hepatitis B Virus for its production and transmission. HDV depends on the Hepatitis B surface antigen provided by the HBV that the former uses to form its envelope of particles (Handa, Yamaguchi, 2006). Although HDV is considered as a satellite virus of HBV, it does not present the same sequence as the later and it its replication is not dependent on the HBV (Hepatitis D Virus, Classification).

The disease may be transmitted through infected blood and blood products, infected needles, through birth (from mother to new born) and through sexual relations, with increased risks of infection in male homosexual relations in males infected with HBV (World Health Organization, 2009; Stanford University Website, 2005).

The incubation period for the BDV lasts between 3 and 7 weeks. After this period, the symptoms of the disease are: nausea, lethargy, diarrhea, loss of appetite, and they are non-specific (Stanford Univ. website, 2005). The next phase will add dark urine and stool that has a light color, indicating that the liver is not able to excrete bilirubin at normal levels and the next level after the incubation period will also indicate symptoms of jaundice (yellowness of teguments and membranes) (A.D.A.M., 2009). Some patients may not present these symptoms at all, although they were infected with the virus.

Generally, the symptoms in patients infected with the HDV are tending to be severe and they are more aggravated than in the case of infection with HBV alone. They also depend on the way the patient was infected: co-infection or super-infection. The symptoms in the later form of infection are the most severe. In the case of infection in the later form, the development of the disease leads to fulminant hepatitis and it can become life threatening. Both forms of the infection can lead to a chronic development of the disease, cirrhosis, leaver failure. Transplant is in life threatening stages the only method of treatment that may be successful in saving the patient's life.

The treatment for the disease is palliative since there are no effective treatments. The treatment with a-interferon has produced remissions, but the patients remained positive when tested subsequent to the treatment (WHO, 2009). There are no vaccines for the prevention of the disease caused by infection with Hepatitis D virus, but since it depends on the presence of the HBV and the infection with the later virus can be prevented through vaccination, the conclusion is that prevention is parallel to the protection against infection with HBV. But, once a patient was infected with HBV, there is no vaccine available for the prevention of super-infection with HDV.

The genome that the HDV contains is an RNA virus, negative, single stranded, circular, rod structure. Besides the RNA genome, the protein coat of HDV contains a single protein, in two forms: small (195 aminoacids) and large (214 aminoacids) forms of the antigen encoded by HDV. The approximate length of the genome is 1,7 kb (Handa, Yamaguchi, 2006). So far, it is the only human disease associated virus that is similar to viruses associated with plant diseases (idem, 2006).

The genome is replicated by cellular polymerases.

"Replication of HDV. Viral particles consist of HDV RNA (black lines) and HDV antigen (blue) encapsidated by HBsAg (red). Picture From: Heller T, Hoofnagle JH. (2003). Denying the wolf access to sheep's clothing. Journal of Clinical Investigation. 112: 319-21" (http://www.stanford.edu/group/virus/delta/2005/newresearcha.html)

The infections with the HDV can occur in two ways are dependent on the HBV. It can wither be simultaneous or occur in a patient who was previously infected with HBV. The se forms of infection are called: co-infection, respectively super-infection (Stanford University website, 2005; Hepatitis D Foundation, 2009).

HDV presents three genotypes, with many variants and further researches have shown that there might be additional genotypes. These genotypes have a geographical distribution. While genotype I is present all over the world, genotype II is found exclusively in the regions form East Asia and genotype III in South America, in the Northern countries. The first genotype is the most common form in the viral infection with the HDV and has the largest area of occurrence (Handa, Yamaguchi, 2006).

The replication of the genome depends on the small form of delta antigen protein, while the large form of the latter was found to determine the assembly of the virus particles. The replication process is following a phase of self-cleavage and ligation through ribozymes that are supplied by the genome (idem, 2006, Stanford University Website, 2005; WHO, 2009).