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 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 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.