Thyroid disturbance related to chronic hepatitis C infection: role of CXCL10

Abstract

The associaTion between chronic hepatitis C (HCV) infection and thyroid autoimmune disorders (AITD) is controversial, but may occur or worsen during alpha-interferon treatment [1]. A large study observed slightly increased risk for thyroiditis in HCV-infected patients (hazard ratio = 1.06, 95% CI = 1.01-1.11) [2] and a recent review suggested a weak association in comparisons to hepatitis B (HBV) infected and control populations (odds ratio = 1.6, 95% CI=1.4-1.9). The authors suggested that differences in geographical distribution, genetic variability and environmental cofactors abstract. Association between autoimmune thyroid diseases (AITD) and hepatitis C is controversial, but may occur or worsen during alpha-interferon treatment. The mechanism responsible for autoimmune diseases in infected patients has not been fully elucidated. This study aims to evaluate the frequency of AITD in chronic hepatitis C and the association of chemokine (CXC motif) ligand 10 (CXCL10) and AITD. One hundred and three patients with chronic hepatitis C and 96 controls were prospectively selected to clinical, hormonal, thyroid autoimmunity and ultrasound exams, besides thyroxinebinding globulin (TBG) and CXCL10 measurements and hepatic biopsies. The frequency of AITD among infected subjects was similar to controls. TT3 and TT4 distributions were right shifted, as was TBG, which correlated to both of them. Thyroid heterogeneity and hypoechogenicity were associated with AITD. Increased vascularization was more prevalent in chronic hepatitis C.CXCL10 was higher in infected patients (p=0.007) but was not related to thyroid dysfunction. Increase in CXCL10 levels were consistent with hepatic necroinflammatory activity (p=0.011). In summary, no association was found between chronic hepatitis C and AITD. Infected subjects had higher TT3 and TT4 which were correlated to TBG. Increased CXCL10 was not associated to thyroid dysfunction in HCV-infected population.

Thyroid Disturbance in Patients with Chronic Hepatitis C Infection: A Systematic Review and Meta-analysis

“…Among the 12 studies, hypothyroidism was reported in 11 [7,[15][16][17][18][19][20][21][22][23][24], while hyperthyroidism in 5 studies [16,20,21,23,24]. TGAb was covered in 8 studies [7,15,17,18,[20][21][22][23], TPOAb in 6 studies [16,17,[20][21][22][23] and ATMA in 5 studies [6,7,15,19,22].…”

“…Study characteristics are shown in Table I. The design of these studies was cross-sectional [17,22], case-control [7,16,[19][20][21]23] or cohort (prospective control) [6,18,24,25]. A total of 1,735 HCV-infected and 1,868 non-HCV infected subjects were involved.…”

“…Eleven studies reported the prevalence of hypothyroidism, which involved 1,605 patients in HCV group and 1,626 in the non-HCV group [7,[15][16][17][18][19][20][21][22][23][24]. The prevalence of hypothyroidism was significantly higher in the HCV group than in the non-HCV group (OR, 3.10; 95% CI 2.19-4.40 [I 2 =0.0%]) (Fig.…”

“…Five studies involving 1,117 HCV infected subjects and 1,092 non-HCV infected subjects reported the prevalence of hyperthyroidism for each group [16,20,21,23,24]. The HCV group and non-HCV group comprised 67 (6.0%) and 64 (5.86%) patients with hyperthyroidism, respectively.…”

Hepatitis C virus infection and thyroid autoimmune disorders: A model of interactions between the host and the environment

“…The chronic stimulation results in: AutoAbs production (clonal B lymphocyte expansion and Th2 response), anti-apoptotic effects (translocation with Bcl-2 activation and prolonged survival of lymphocytes), drive for autoimmunity (binding of protein E2 to CD81, that mediate attachment on hepatocytes), increased cytokine and chemokine secretion (IFN-γ and Th1 response with IFN-γ inducible chemokines such as C-X-C motif chemokine 10 or CXCL10, in order to stop viral spread; IL-8) and upregulation of CXCL10 by NS5a [56][57][58][59] . However, no association has been found between chronic hepatitis C with increased CXCL10 and AITD [60] .…”