Hepatitis C virus: Molecular biology & current therapeutic options

Introduction
Hepatitis C is a complex liver disease. Its medical
importance and the need to rapidly identify new
therapeutic approaches has resulted in intensive study
of its causative agent, hepatitis C virus (HCV). Humans
are the only known natural hosts of HCV. Even after
two decades since its discovery, HCV continues to be
a major cause of concern and a huge burden on public
health systems worldwide. The WHO estimates that
a minimum of 3 per cent of the world’s population is
chronically infected with HCV1,2.
HCV is a prototype member of the Hepacivirus
genus (from the Greek hepar, hepatos, liver) and is
further classified into at least seven major genotypes
that differ by about 30 per cent in their nucleotide
sequence. These genotypes (1, 2, 3, 4, 5, 6 & 7) show
differences with regard to their worldwide distribution,
transmission and disease progression3, 4. These
genotypes have been further classified into sub-types
(a, b, c, d, etc). In fact, HCV circulates in infected
individuals as a population of diverse but closely
related variants referred to as “quasispecies”.
HCV is most commonly spread by direct
contact with infected blood and blood products.
Availability of injectable therapies and drugs has
had a remarkable influence on HCV epidemiology.
The incubation period of HCV, though ranging up
to several months, averages 6-8 wk. HCV infection
is often asymptomatic, making it a very difficult to
detect it at an early stage. This is the major reason
why early treatment is difficult. Therefore, hepatitis C
is often referred to as a “silent disease”. In a majority
of infected people, virus infection does not resolve
naturally. Neutralizing antibodies appear to be
produced during the course of a natural infection, yet
the virus mutates to escape surveillance5. When liver
fails to clear the virus, the individuals become chronic
carriers. However, within this chronically infected
population the disease outcomes vary, it can be mild
(minimal inflammation of the liver) or severe and can
lead to scar tissue formation (Fig. 1). Chronic infection
eventually causes cirrhosis leading to hepatocellular
carcinoma (HCC) and ultimately death. Currently,
there is no vaccine to prevent hepatitis C.
Liver steatosis occurs in more than 50 per cent of
the patients with chronic hepatitis C (CHC) infection.
Some individuals with CHC may report non specific
symptoms such as fatigue, muscle aches, nausea and
pain in the right upper quadrant. Antibodies directed
against several HCV proteins can be detected in
chronic patients. A variety of autoimmune and
immunecomplex-mediated diseases have also been
associated with chronic HCV infection, autoimmune
thyroiditis being one of them6.