Papers

High prevalence of serum antibodies to hepatitis C virus in patients with Hashimoto's thyroiditis

Service d'Hepatogastroenterologie, Hopital Jean Verdier, 93140 Bondy Cedex, France Laboratoire d'Immunologie, Hopital Saint Antoine, 75012 Paris Service de Microbiologie, Hopital Avicenne, 93000 Bobigny Service de Medecine Nucleaire, Hopital Pitie Salpetriere, 75013 Paris Service d'Endocrinologie, Hopital Saint Antoine, 75012 Paris Service d'Endocrinologie, Hopital Jean Verdier, 93140 Bondy Laboratoire d'Immunologie Clinique, Hopital Cochin, 75014 Paris Correspodence to: Professor Beaugrand.

Given the reports of thyroid dysfunction and various autoimmune disorders such as Sjogren's syndrome in patients infected with hepatitis C virus,^1,2 we hypothesised a link between autoimmune thyroid disease, mainly Hashimoto's thyroiditis, and such infection. We looked for antibodies to hepatitis C virus in the serum of patients with thyroid disease.

Subjects, methods, and results

We studied stored serum samples from 200 patients (190 women) with thyroid disease (simple goitre (n=50), Graves' disease (n=50), and Hashimoto's thyroiditis (n=50)) randomly selected from all patients seen at five centres between 1987 and 1992.

Thyroid function was assessed by standard radioimmunoassays for serum thyroxine, triiodothyronine, and thyroid stimulating hormone. Receptor antibodies for thyroid stimulating hormone were detected with radioreceptor assay (Trak-asay, Henning Laboratories, Berlin). Serum antibodies to thyroid microsome and thyroperoxidase were used to diagnose Hashimoto's thyroiditis, depending on the centre. Serum antibodies to thyroid microsome were detected with indirect immunoinflorescence assay by using cryostat sections of human thyroid or by passive haemagglutination with a commercial kit (Thymune-M, Wellcome Laboratories, Beckenham). Serum antibodies to thyroperoxidase were assessed by radioimmunoassay (Dynotest anti- TPO, Henning Laboratories, Berlin) and antibodies to thyroglobulin by passive haemagglutination (Thymune-T, Wellcome Laboratories, Beckenham).

A second generation enzyme linked immunosorbent assay (ELISA) (Diagnostics Pasteur, Marnes la Coquette, France) was used to detect antibodies to hepatitis C virus. Samples yielding positive results were retested with a second generation recombinant immunoblot assay (RIBA, Ortho Diagnostic Systems, Raritan, New Jersey). Serum concentrations of immunoglobulin G were assayed by laser nephelometry in the serum of patients with Hashimoto's thyroiditis.

Fisher's exact test and the Mann-Whitney U test were used for statistical analysis. Results are expressed as means (SD).

The table summarises the results of the assays. No significant difference was noted for age or serum concentration of immunoglobulin G in patients with Hashimoto's thyroiditis with or without hepatitis C virus antibodies.

Comment

We found a higher prevalence of serum hepatitis C virus antibodies in patients with Hashimoto's thyroiditis than in those with any other thyroid disease. Among patients with Hashimoto's thyroiditis those with a positive result on ELISA and a negative result on immunoblot assay had lower serum concentrations of immunoglobulin G than those with positive results in both tests, though this result was not significant. This suggests that false positive reactions because of high serum concentrations of immunoglobulin G are unlikely.

The disappearance of hepatitis C virus is followed by decreasing titres of serum hepatitis C virus antibodies, which become undetectable after several months or years of follow up,³ though those patients with negative results in both assays may have low titres of antibodies not recognised by the highly specific but less sensitive immunoblot assay. If the result of the immunoblot assay becomes negative before the ELISA result, a few of these patients may be in fact infected with hepatitis C virus. The high prevalence of such antibodies in patients with Hashimoto's thyroiditis compared with other groups of thyroid disease and with the normal population⁴ suggests that hepatitis C virus may be responsible for triggering Hashimoto's thyroiditis. The role of another agent or epidemiological factor related to hepatitis C virus, however, cannot be excluded.

Results of assays* for serum antibodies to hepatitis C virus in four groups of
patients with thyroid disease
-------------------------------------------------------------------------------------------------------------------------
                                              ELISA                                             RIBA
                              -------------------------------------------------------------------------------------------
Type of thyroid disease          Negative result    Positive result      Indeterminate result     Positive result
-------------------------------------------------------------------------------------------------------------------------
Simple goitre                           50                 0                      -                      -
Graves' disease                         49                 1                      1                      -
Myxoedema                               48                 2                      -                      1
Hashimoto's thyroiditis                 38                12(dagger)              -                      5
-------------------------------------------------------------------------------------------------------------------------
Total                                                     15(double dagger)       1                      6
-------------------------------------------------------------------------------------------------------------------------
 RIBA=recombinant immunoblot assay.
 *Difference for detection of hepatitis C antibodies in patients with
Hashimoto's thyroiditis v other thyroid diseases combined, P<0.0001 for ELISA
and P=0.01 for recombinant immunoblot assay.
 (dagger)24% (95% confidence interval 12% to 36%).
 (double dagger)75% of all patients with thyroid disease.

Hepatitis C virus is not the first viral agent suspected of initiating an autoimmune thyroid process. Some viruses may be implicated in animals, and the role of retroviruses has been suggested in humans.⁵ The possible role of infection with hepatitis C virus in triggering Hashimoto's thyroiditis does not rule out other agents such as exoviruses or endoviruses,⁵ and other detailed studies of such associations are needed.

We thank Professor J P Luton for providing the serum samples.

1. Manns MP. Autoimmunity and hepatitis C virus. In: Miguet JP, Dhumeaux D, eds. Progress in hepatology 93. Paris: John Libbey Eurotext, 1993:79-87.
2. Haddad J, Deny P, Munz-Gotheil C, Ambrosini JC, Trinchet JC, Pateron D, et al. Lymphocytic sialadenitis of Sjogren's syndrome associated with chronic hepatitis C virus liver disease. Lancet 1992;339:321-3. [Medline]
3. Alter HJ, Purcell RH, Shih JW, Melpolder JC, Houghton M, Choo QL, et al. Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis. N Engl J Med 1989;321:1494-500. [Abstract]
4. Esteban JI, Genesca J, Alter HJ. Hepatitis C: molecular biology, pathogenesis, epidemiology, clinical features, and prevention. In: Boyer JL, Ockner RK, eds. Progress in liver disease. Philadelphia: WB Saunders, 1992:219-38.
5. Ciampolillo A, Marini V, Mirakian R, Buscema M, Schulz T, Pujol- Borrell R, et al. Retrovirus-like sequences in Graves' disease: implications for human autoimmunity. Lancet 1989;i:1096-100.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    StumbleUpon    Technorati    What's this?

This article has been cited by other articles:

• Antonelli, A., Ferri, C., Fallahi, P., Giuggioli, D., Nesti, C., Longombardo, G., Fadda, P., Pampana, A., Maccheroni, M., Ferrannini, E. (2004). Thyroid involvement in patients with overt HCV-related mixed cryoglobulinaemia. QJM 97: 499-506 [Abstract] [Full text]  
• Wagner, B., Vierhapper, H., Hofmann, H. (1996). Prevalence of hepatitis C virus infection in Hashimoto's thyroiditis. BMJ 312: 640b-641 [Full text]  
• Abdul-Jabbar, M.A., Ehrlich, R.M., Mann, N., Roberts, E.A. (1995). Transient Hypothyroidism in a Child Treated With Alpha-Interferon for Chronic Hepatitis B Infection. CLIN PEDIATR 34: 663-665  
• Leri, O., Sinopoli, M. T., Di Prima, M. A., Di Prima, A. (1995). Hepatitis C virus antibodies and Graves' disease. BMJ 310: 128d-129 [Full text]  
• (1994). HEPATITIS C AND HASHIMOTO'S THYROIDITIS. JWatch General 1994: 6-6 [Full text]