By Dr Ananya Mandal, MD
Hepatitis C is caused by infection with the hepatitis C virus. The hepatitis C virus is a single stranded, enveloped, positive sense RNA virus.
The virus can infect the person and may cause severe inflammation of the liver leading to severe liver damage and long term complications.
The infection usually begins in a gradual manner with vague symptoms like tiredness, loss of appetite, abdominal discomfort, nausea and vomiting, fever etc.
Slowly it may progress to jaundice in about 25% of patients. Of those infected nearly 40% recover fully and the rest become chronic carriers of the infection.
Of these nearly a third develops liver cirrhosis and of those with cirrhosis, up to 20% develop liver cancer.
The hepatitis C virus is an enveloped, single stranded RNA virus with a diameter of about 50 nm. It belongs to the genus (Hepacivirus) within the Flaviviridae family.
The virus primarily affects humans but has been experimentally found to infect chimpanzees as well.
The viral RNA is highly mutable and there is lack of an efficient proofreading mechanism while the virus replicates. This makes the virus undergo evolution with time.
In addition by constantly changing the virus manages to escape host immune system that cannot identify and eliminate the virus effectively.
The highly variable mutation-prone regions of the virus are those that code for the envelope proteins. As the envelope proteins changes in the mutated virus the body fails to recognize it and the immunity fails to eliminate the infection.
As a consequence most hepatitis C infected persons go on to develop chronic infection. In addition this variability prevents or hinders the development of an effective vaccine against Hepatitis C virus.
Genotypes of hepatitis C virus
There are several genotypes of hepatitis C virus. Specifically 11 genotypes with several distinct subtypes have been identified throughout the world.
The genotypes vary in their responsiveness to interferon/ribavirin combination therapy but do not vary in their virulence of pathogenicity.
There are about 100 different strains (numbered 1, 2, 3, etc.) based on the gene sequence differences.
Genotype 1 is generally associated with a poor response to interferon alone. Genotypes 2 and 3 are associated with more favourable responses.
Genotypes 1-3 are found worldwide. Of these types 1a and 1b are the most common, accounting for about 60% of infections worldwide. These occur more commonly in Northern Europe and North America, and in Southern and Eastern Europe and Japan.
Type 2 is less frequently represented than type 1. Type 3 is seen more commonly in south-east Asia.
Genotype 4 is predominantly detected in the Middle East, Egypt, and central Africa while type 5 is found almost exclusively in South Africa. Genotypes 6-11 are widely found across Asia.
Life cycle of the hepatitis C virus
The virus enters the cell and the envelope is removed in the cytoplasm of the cell. Then the viral genome or the RNA transcribes to form a complementary negative-sense RNA molecule. This serves as a template or base for the synthesis of more positive strand RNAs. These would form parts of the new viruses.
The next step is development of the other proteins of the virus - NS-2 and NS-3. Both these steps are mediated by virally encoded RNA-dependent RNA polymerase NS5b.
Reviewed by April Cashin-Garbutt, BA Hons (Cantab)