Hepatitis C and interferon induced thyroiditis

Abstract

Autoimmune thyroid diseases (AITDs) are complex diseases that develop as a result of interactions between genetic, epigenetic, and environmental factors. Significant progress has been made in our understanding of the genetic and environmental triggers contributing to AITD. The major environmental triggers of AITD include iodine, smoking, medications, pregnancy, and possibly stress. In this review we will focus on two well-documented environmental triggers of AITD, hepatitis C virus (HCV) infection and interferon alpha (IFNa) therapy. Chronic HCV infection has been shown to be associated with increased incidence of clinical and subclinical autoimmune thyroiditis (i.e. the presence of thyroid antibodies in euthyroid subjects). Moreover, IFNa therapy of chronic HCV infection is associated with subclinical or clinical thyroiditis in up to 40% of cases which can be autoimmune, or non-autoimmune thyroiditis. In some cases interferon induced thyroiditis (IIT) in chronic HCV patients may result in severe symptomatology necessitating discontinuation of therapy. While the epidemiology and clinical presentation of HCV and interferon induced thyroiditis have been well characterized, the mechanisms causing these conditions are still poorly understood.

Figure 1

IIT develops in genetically predisposed individuals by direct effects of IFNa on the thyroid cell, as well as by immune effects. The HCV infection and IFNa therapy cause secretion of cytokines from thyroid cells and thyroid cell death with release of thyroid antigens. These antigens can be picked by antigen presenting cells (APC’s) and presented to resident T-cells in the thyroid triggering autoimmune thyroiditis.