ABSTRACT

Hepatitis C virus carries a positive single-stranded RNA genome encoding three structural and a number of non-structural proteins, belonging to the flavivirus family. It replicates within cells in a membranous web within the cytoplasm. It infects hepatocytes. It bears many clinical and epidemiologic similarities to hepatitis B virus – both are blood–borne, and both can give rise to chronic infection. Infection with HCV arises from blood-to-blood exposure via contaminated blood or blood-product transfusion or sharing of contaminated needles and injecting paraphernalia. Mother-to-baby transmission occurs but is unusual. The WHO estimates around 70 million people are currently infected with HCV. The virus induces potent innate immune responses and chronic infection gives rise to a hyperstimulated immune state within the liver. Clearance of infection at the acute stage is associated with generation of broadly reactive neutralizing antibodies and a broad T-cell response. Acute infection is usually asymptomatic but is cleared in less than half of all cases. Chronic infection gives rise to immune-mediated liver damage and eventual cirrhosis, with an additional increased risk of hepatocellular carcinoma. Diagnosis is by anti-HCV detection, a marker of past infection, followed by HCV RNA detection which distinguishes between past and current infection. Treatment of chronic HCV infection with combinations of directly acting agents targeted at key viral proteins (NS3, NS5a and NS5b) is almost always successful in achieving viral clearance. There is currently no vaccine against HCV infection.