Susceptibility to thyroid disorders in hepatitis C.
OBJECTIVE
Autoimmune thyroid disorders (AITDs) are reported, especially during interferon treatment, in chronic HCV infection, in which non-organ-specific autoantibodies (NOSAs) are common. We wondered whether seropositivity for NOSA is associated with susceptibility to AITDs.


METHODS
We evaluated thyroid function and antithyroglobulin and antithyroperoxidase antibodies in 348 Italian patients with chronic hepatitis C (34% NOSA-positive), 196 patients (33% NOSA-positive) of whom received interferon treatment.


RESULTS
At baseline, thyroid disorders were significantly more frequent in liver/kidney microsomal antibody type 1 (LKM1)-positive patients (29% vs 9%, P < .005). Similarly, on interferon therapy de novo autoimmune thyroid markers and/or symptomatic thyroid disorders appeared more often in LKM1-positive patients (50% vs 3%, P < .0001). Both female sex and LKM1 positivity were predictors of AITD, but only the latter remained significant after logistic regression analysis. Cross-reactivity to all 7 linear epitopes encoding homologous amino acid sequences shared by the HCV polyprotein, CYP2D6 (the LKM1 autoantigen), and thyroperoxidase was detected in 86% LKM1-positive HCV patients with clinical thyroid disorders, but in none of the LKM1-positive or negative HCV patients without thyroid disease, and none of an HCV-negative control group comprising subjects with LKM1-positive autoimmune hepatitis or AITD without liver disease ( P < .0001).


CONCLUSIONS
Patients receiving interferon therapy for hepatitis C seropositive for LKM1 are susceptible to develop AITDs, in association with treatment. Molecular mimicry and epitope spreading are potential pathogenic mechanisms.
Muratori
Luigi
L
Department of Internal Medicine, Cardioangiology, Hepatology, Alma Mater Studiorum University of Bologna, Bologna, Italy. luigi.muratori@unibo.it
Bogdanos
Dimitrios P
DP
Muratori
Paolo
P
Lenzi
Marco
M
Granito
Alessandro
A
Ma
Yun
Y
Mieli-Vergani
Giorgina
G
Bianchi
Francesco B
FB
Vergani
Diego
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D001323:Autoantibodies / Q000276:immunology*; D004198:Disease Susceptibility; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D018937:Hepatitis C Antibodies / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating / Q000276:immunology*; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics; D012189:Retrospective Studies; D013959:Thyroid Diseases / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D013963:Thyroid Hormones / Q000097:blood
D000998:Antiviral Agents; D001323:Autoantibodies; D018937:Hepatitis C Antibodies; D018828:Immunoglobulins, Thyroid-Stimulating; D016898:Interferon-alpha; D012367:RNA, Viral; D013963:Thyroid Hormones; C060729:anti-liver kidney microsome antibody