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Hepatitis Viruses
General Concepts
Viral hepatitis has emerged as a major public health problem
throughout the world affecting several hundreds of millions of people.
Viral hepatitis is a cause of considerable morbidity and mortality in
the human population, both from acute infection and chronic sequelae
which include, in the case of hepatitis B, C and D, chronic active
hepatitis and cirrhosis. Hepatocellular carcinoma which is one of the
ten most common cancers worldwide, is closely associated with
hepatitis B, and at least in some regions of the world with hepatitis C
virus.
Hepatitis A virus
Hepatitis A virus (HAV), classified as hepatovirus, is a small,
unenveloped symmetrical RNA virus which shares many of the
characteristics of the picornavirus family, and is the cause of
infectious or epidemic hepatitis transmitted by the fecal-oral route.
Hepatitis B virus
Hepatitis B virus (HBV), a member of the hepadnavirus group,
double-stranded DNA viruses which replicate, unusually, by reverse
transcription. Hepatitis B virus is endemic in the human population
and hyperendemic in many parts of the world. A number of variants
of this virus have been described.
Hepatitis C virus
Hepatitis C virus (HCV), is an enveloped single-stranded RNA virus
which appears to be distantly related (possibly in its evolution) to
flaviviruses, although hepatitis C is not transmitted by arthropod
vectors. Several genotypes have been identified. Infection with this
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more recently identified virus is common in many countries. Hepatitis
C virus is associated with chronic liver disease and also with primary
liver cancer in some countries.
Hepatitis D virus
Hepatitis D virus (HDV) is an unusual, single-stranded, circular RNA
virus with a number of similarities to certain plant viral satellites and
viroids. This virus requires hepadna virus helper functions for
propagation in hepatocytes, and is an important cause of acute and
severe chronic liver damage in many regions of the world.
Hepatitis E virus
Hepatitis E virus (HEV), the cause of enterically-transmitted non-A,
non-B hepatitis, is another non-enveloped, single-stranded RNA
virus, which shares many biophysical and biochemical features with
caliciviruses. The most similar genome to HEV is found in a plant
virus, beet necrotic yellow vein virus, and there are similarities in the
functional domains to rubella virus. Final taxonomic classification is
yet to be agreed upon.
Hepatitis E virus is an important cause of large epidemics of acute
hepatitis in the subcontinent of India, Central and Southeast Asia, the
Middle East, parts of Africa and elsewhere. This virus is responsible
for high mortality (15–20%), during pregnancy particularly during the
third trimester.
Diagnosis
Various serologic tests are available for hepatitis A, including
immune electron microscopy, complement-fixation, immune
adherence hemagglutination, radioimmunoassay, and enzyme
immunoassay. Immune adherence hemagglutination, which had been
widely used, is moderately specific and sensitive. Several methods of
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radioimmunoassay have been described; of these, a solid-phase type
of assay is particularly convenient, very sensitive, and specific. Very
sensitive enzyme immunoassay techniques are used widely.
Only one serotype of hepatitis A virus has been identified in
volunteers infected experimentally with the MS-1 strain of hepatitis
A, in patients from different outbreaks of hepatitis in different
geographic regions, and in random cases of hepatitis A.
Isolation of virus in tissue culture requires prolonged adaptation and
it is, therefore, not suitable for diagnos
Vaccine Development
Problems in vaccine development include the sequence diversity
between viral groups and the substantial sequence heterogeneity
among isolates in the N-terminal region of E2/NS1. Neutralizing
antibodies have not been identified so far. The virus has not been
cultivated in vitro (cf. Yellow fever flavivirus, which has been
cultured and from which vaccines have been prepared). Nevertheless,
approaches to vaccine development could be based on techniques
used for the development of vaccines against the Flaviviruses and
Pestiviruses.