2000 IRISH SCIENTIST YEAR BOOK

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New insights in to the natural history of hepatitis C virus infection

Health Research Board & Cork University Hospital
Liam Fanning

A viral version of the 'invasion of the body snatchers' - the Hepatitas C virus invades the human liver.

Chronic hepatitis C infection is a ubiquitous disease, affecting over 200 million people worldwide. The hepatitis C virus (HCV) is spread by exposure to infected blood or blood products. The most striking feature of hepatitis C virus infection is the tendency toward chronicity. The human leukocyte associated antigen (HLA) is a host-encoded protein that presents bacterial and viral proteins to the infected individual's immune system. The HLA has been shown to influence host response to the HIV and the hepatitis B virus.

Researchers at the Hepatitis C Unit, Cork, Department of Medicine, Cork University Hospital, have assessed the likely influence of host HLA on the ability of infected individuals to eliminate the HCV. The study population was infected from a single source, with a single type of the hepatitis C virus, and the year of infection was known for each individual. The study population was equally divided between those who had evidence of exposure to the HCV, but who had cleared the virus, and those who were persistently infected with the virus.

In a series of experiments, DNA was isolated from the blood of these individuals. Their genetic profile was determined molecularly at two specific locations on chromosome 6. Analysis of this genetic data revealed that presence of a particular HLA group was associated with a greater likelihood of clearance of the hepatitis C infection. Additional analysis identified a HLA gene, which was associated with persistent hepatitis C infection in this study population. Evidence from the study may lead to the identification of crucial protein segments from the HCV important for immune system mediated clearance.

Chronic hepatitis C is characterized by persistent viraemia (i.e. the continuous presence of detectable virus), the natural variation of which is undefined. Researchers at the Hepatitis C Unit have evaluated the amount of virus present in the blood over an extended period of patient follow-up and developed a model for predicting change in viral load over time in their study population. The results of this research suggest that viral load appears to increase over time in the chronically infected individual. This model, which is currently undergoing prospective evaluation, may enable the prediction of when chronically infected individuals are likely to have a serum viral load correlated with likely response to anti-viral therapy.

The ongoing goal of the Hepatitis C Unit is to define the viral and host factors that influence the natural progression of hepatitis C virus infection.



Contact: Liam Fanning PhD,
Hepatitis C Unit, Department of Medicine, Clinical Sciences Building,
Cork University Hospital;
Tel: +353-21-901281; Fax: +353-21-345300;
E-mail: l.fanning@ucc.ie