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Genetic factors predicting response to interferon treatment for viral hepatitis C
  1. Peter Stärkel
  1. Dr Peter Stärkel, Department of Gastroenterology, St. Luc University Hospital, Av. Hippocrate 10, 1200 Brussels, Belgium; peter.starkel{at}

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Since completion of the human genome and HapMap projects it is likely that an increasing number of studies dealing with genetic associations in specific diseases will be published in medical journals. Hepatitis C and especially its response to antiviral treatment does not constitute an exception to this rule. It has been known for quite a long time that viral factors such as genotype and viral load have a major influence on the outcome of antiviral treatment.1 Nevertheless, researchers have become increasingly aware that host genetic factors including ethnicity, human leucocyte antigens, cytokine production and differences in T cell immune responses can modulate the response to antiviral treatment and viral clearance.2 3 In this issue of Gut (see page 10.1136/gut.2007.129478), Persico et al report on single nucleotide polymorphisms (SNPs) of suppressor of cytokine signalling 3 (SOCS3) being positively and negatively associated with response to antiviral therapy in hepatitis C virus (HCV) genotype-1-infected patients.4 Interestingly, these data were generated from peripheral mononuclear blood cells (PMBCs), a material that would be easily available for large-scale studies in the future. The concept of SOCS3 being involved in modulating antiviral response mechanisms is appealing to the scientific community. SOCS3 acts as a negative regulator of the cytokine-induced JAK–STAT (Janus kinase–signal transducer and activator of transcription) pathway. As a consequence of a classical negative feedback circuit, SOCS3 inhibits the cytokine receptor-associated JAK tyrosine kinase through either direct interaction with JAKs or indirect inhibition by binding to specific sites on the receptor.5 6 Inhibition of JAKs leads in turn to deficient STAT phosphorylation and dimerisation required for nuclear translocation of STATs and ultimately to blockage of transcriptional activity of STAT-responsive genes involved in regulation of immune responses and maintaining immunological homeostasis.6 Interferons (IFNs) are naturally occurring proteins that induce an antiviral state …

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  • Competing interests: None.

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