Hepatitis C virus: current concepts and future challenges
Hepatitis C virus (HCV) is a global infection, with an estimated 170 million people affected.1 The geographical distribution is of some interest as it gives clues as to the history and transmission of the virus. It appears there are endemic strains, which have persisted in specific locations for many centuries. These can be readily identified by viral genotype—for example, Genotype 2 is a strain which evolved in West Africa, while Genotype 6 evolved in South East Asia.2 In the last century, there have been iatrogenic outbreaks leading to a massive spread of specific subtypes in countries such as Egypt (Genotype 4A).3 There was also global spread of certain strains, most notably Genotype 1 within Europe and North America, and more recently Genotype 3A in European intravenous drug user (IDU) populations.4

HCV heterogeneity is huge, based on its capacity to develop mutation through its error-prone polymerase, and its very long co-evolutionary history with man. This is a major challenge for drug design and vaccines. Clinically, genotypic information on the virus is of major importance in defining response to conventional as well as newer therapies.1,4

Chronic HCV infection is now a leading cause of hepatic failure requiring transplantation in the west. Cirrhosis associated with HCV is also linked to the development of hepatocellular carcinoma, although unlike hepatitis B virus (HBV) this does not occur in pre-cirrhotic states. Chronic HCV infection is also associated with a number of extra-hepatic diseases, linked to B cell hyper-activation and potentially also chronic antigenemia—most notably mixed essential cryoglobulinaemia.5

Acute hepatitis C is actually a rare clinical presentation, despite the widespread nature of the virus. Typically, acute hepatitis is mild and may be clinically very subtle, with a delay of several weeks before a rise in alanine transaminase (ALT) is …