Hepatitis C and interferon induced thyroiditis
Introduction
While abundant data point to a strong genetic susceptibility to the development of autoimmune thyroid disease (AITD), including Grave's disease (GD) and Hashimoto's thyroiditis (HT) (reviewed in [1]), environmental factors also play an important role. Since monozygotic twins do not show 100% concordance for AITD non-genetic factors must also play a role. Indeed, a recent twin study estimated that about 20% of the liability to the development of GD is attributable to non-genetic factors [2]. The environmental factors postulated to precipitated AITD include iodine [3], [4], medications, such as amiodarone and interferon alpha [5], infections [6], smoking, and possibly stress (reviewed in [7]). Recently, HCV infection [8] and interferon alpha (IFNa) therapy [9] emerged as the most substantiated environmental triggers of AITD.
Section snippets
Infection and AITD
One of the most intriguing environmental triggers of autoimmune thyroid diseases is infection (reviewed in [10]). Evidence supporting infectious cause of AITD include seasonality in the incidence of AITD [11], geographic variation [12], and serological evidence for a recent bacterial or viral infection [13]. Several infectious agents have been implicated in the pathogenesis of AITD including Yersinia enterocolitica [14], [15], [16], [17], Coxsackie B virus [18], retroviruses [19], [20], [21],
Interferon induced thyroiditis (IIT)
Interferon alpha (IFNa) is a type I interferon that has been widely used as a therapeutic agent mostly, for infectious and malignant diseases [52]. IFNa binds to interferon receptors, and activates various signaling pathways, including the JAK-STAT pathway, and the MAP kinase pathway leading to transcription of target proteins which mediate its immune and anti-tumor effects [53], [54], [55]. One of the most remarkable successes of IFNa as a therapeutic agent has been in the treatment of chronic
Conclusions
One of the commonest complications of IFNa therapy for chronic hepatitis C infection is interferon induced thyroiditis (IIT) [9]. Recent data supports the notion that IFNa triggers thyroiditis in genetically predisposed individuals by both direct thyroid-toxic mechanisms and immune-modulatory mechanisms [77]. It is likely that the HCV infection itself contributes to the initiation of thyroid autoimmunity [51]. Since IIT is very common in HCV patients receiving IFNa therapy all patients should
Acknowledgments
This work was supported in part by: DK61659 from NIDDK and a VA Merit Award (to YT).
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