When the immune system causes harm

As I have mentioned in my previous posts I am interested in Hepatitis C. There are currently over 170 million people infected with this virus worldwide. The long-term complication of Hepatitis C are cirrhosis and hepatocellular carcinoma. These complications often lead to liver transplant in the Hepatitis C patient.

As we learn more about HepatitisC and the immune response that is raised in attempts to clear the infection it becomes more clear that the inflammation intended to wipe out the virus is harming the liver and leading to cirrhosis and likely hepatocellular carcinoma.

Following viral infection there is activation of several pre-inflammatory mediators (chemokines -cytokines) that recruit immune cells into the liver. Once in the liver the immune cells are induced to generate an anti-viral immune response (T helper 1 cells secrete IFN-gamma and IL-2). If in the short-term the infection is not cleared the liver is set-up for a chronic inflammatory response (inflammation, regeneration and fibrosis). There is increasing evidence that different chemokines and receptors play roles at different stages in the infection.

Identification of serum markers for this inflammatory chemokine activity could help stage the chronic Hepatitis C viral process. Staging would assist with treatment options. Additionally, identification of an antagonist for this interaction would provide a treatment for liver inflammation, but would allow the virus to persist. Decreasing inflammation would potentially decrease cirrhosis and carcinoma. The concern is the cost of chronic Hepatitis C infection without the inflammation to hold it at bay.

There continue to be many unanswered questions for Hepatitis C, however the pieces of the puzzle continue to grow and fit into an explanation.

Reference -

Zeremski M, et al. The role of chemokines as inflammatory mediators in chronic hepatitis C virus infection. J Viral Hepat. 2007; 14(10): 675-87

Wald, O., et al. Chemokines in hepatitis C virus infection: pathogenesis, prognosis and therapeutics. Cytokine. 2007; 39(1): 50-62