Article information
Abstract
Objective
The treatment of the chronic hepatitis C (HCV) with α-interferon is associated with thyroid dysfunction (TD). The aim of this study was to evaluate thyroid function outcome among patients with chronic HCV under treatment with conventional interferon (IFN) or peguilated interferon (PEG-IFN) in association with ribavirin.
Patients and MethodsWe studied 293 patients with chronic HCV, submitted to drug therapy for 24 or 48 weeks. Initially, we evaluated FT4, TSH, TPOAb, TgAb, and continued to monitor FT4 and TSH every three months during therapy and six months thereafter.
ResultsAt baseline, TD prevalence was 6.82% (n=20); 6.14% hypothyroidism; 0.68% hyperthyroidism. TPOAb was present in 5.46% of euthyroid patients. Out of 273 euthyroid patients at baseline, 19% developed TD: 17.2% hypothyroidism; 1.8% hyperthyroidism; 5.1% destructive thyroiditis (DT). 90% of TPOAb-positive patients at baseline developed hypothyroidism vs 14.5% of TPOAb-negative patients (p<0.001). On average, TD occurred after 25.8±15.5 weeks of treatment. 87.2% of patients who developed hypothyroidism did so during the first therapeutic cycle (p=0.004; OR=3.52; 95% CI = 1.36–9.65). Patients infected with genotype 1 virus were 2.13 times more likely to develop hypothyroidism (p = 0.036; 95% CI = 1.04–4.38). Hypothyroid and DT patients presented higher TSH levels before-treatment than patients who had remained euthyroid (p<0.001; p=0.002, respectively). DT patients presented lower qALT (p = 0.012) than euthyroid patients.
ConclusionHypothyroidism was the most frequent TD, especially during the first cycle of α-interferon. Genotype 1 virus was associated with a risk two times higher for developing the illness. There was no need to interrupt or to change HCV treatment. Therefore, approximately 34% of TD was transient.
Keywords:
hypothyroidism
hepatitis C, chronic
interferon-α
Full text is only aviable in PDF
References
[1.]
S. Bellentani, C. Tiribelli.
The spectrum of liver disease in the general population: lessons from the Dionysos study.
J Hepatol, 35 (2001), pp. 531-537
[2.]
T. Poynard, P. Marcellin, S.S. Lee, et al.
Randomized trial of interferon a2b plus ribavirin for 48 weeks or for 24 weeks versus interferon a2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus.
Lancet, 352 (1998), pp. 1426-1432
[3.]
R.C. Tam, B. Pai, J. Bard, et al.
Ribavirin polarizes human T cell responses toward a type 1 cytokine profile.
J Hepatol, 30 (1999), pp. 376-382
[4.]
L.K.H. Koh, F.S. Greenspan, P.P.B. Yeo.
Interferon-α induced thyroid dysfunction: three clinical presentations and review of the literature.
Thyroid, 7 (1997), pp. 891-896
[5.]
O. Dalgard, K. Bjoro, K. Hellum, et al.
Thyroid dysfunction during treatment of chronic hepatitis C with interferon-α: no association with either interferon dosage or efficacy of therapy.
J Int Med, 251 (2002), pp. 400-406
[6.]
C. Carella, G. Mazziotti, G. Amato, et al.
Interferon-α related thyroid disease: pathophysiological, epidemiological, and clinical aspects.
J Clin Endocrinol Metab, 89 (2004), pp. 3656-3661
[7.]
M.F. Prummel, P. Lauberg.
Interferon-α and autoimmune thyroid disease.
Thyroid, 13 (2003), pp. 547-551
[8.]
Y. Tomer, J.T. Blackard, N. Akeno.
Interferon alpha treatment and thyroid dysfunction.
Endocrinol Metab Clin N Am, 36 (2007), pp. 1051-1066
[9.]
J.T. Blackard, N. Kemmer, K.E. Sherman.
Extrahepatic replication of HCV: insights into clinical manifestations and biological consequences.
Hepatology, 44 (2006), pp. 15-22
[10.]
M.W. Fried.
Side effects of therapy of hepatitis C and their management.
Hepatology, 36 (2002), pp. 237-244
[11.]
D.M. Evon, A. Verma, K. Simpson, et al.
Psychiatric symptoms during interferon treatment for hepatitis C: experiences from a tertiary care hepatology centre.
Aliment Pharmacol Ther, 27 (2008), pp. 1071-1080
[12.]
I.S. Fentiman, B.S. Thomas, F.R. Balkwill, et al.
Primary hypothyroidism associated with interferon therapy of breast cancer.
Lancet, 8438 (1985), pp. 1166
[13.]
S. Sachithanandan, G. Clarke, J. Crowe, et al.
Interferon-associated thyroid dysfunction in anti-D-related chronic hepatitis C.
J Interf Cytok Res, 17 (1997), pp. 409-411
[14.]
D. Pateron, D.J. Hartmann, J.C. Duclos-Vallee, et al.
Latent autoimmune thyroid disease in patients with chronic HCV hepatitis.
J Hepatol, 16 (1992), pp. 244-245
[15.]
A. Antonelli, C. Ferri, P. Fallahi, et al.
Thyroid disorders in chronic hepatitis C virus infection.
Thyroid, 16 (2006), pp. 563-572
[16.]
A. Tran, J.F. Quaranta, S. Benzaken, et al.
High prevalence of thyroid autoantibodies in a prospective series of patients with chronic hepatitis C before interferon therapy.
Hepatol, 18 (1993), pp. 253-257
[17.]
D. Preziati, L. La Rosa, G. Covini, et al.
Autoimmunity and thyroid function in patients with chronic active hepatitis treated with recombinant interferon alpha-2a.
Eur J Endocrinol, 132 (1995), pp. 587-593
[18.]
L. Fernandez-Soto, A. Gonzalez, F. Escobar-Jimenez, et al.
Increased risk of autoimmune thyroid disease in hepatitis C vs hepatitis B before, during, and after discontinuing interferon therapy.
Arch Int Med, 158 (1998), pp. 1445-1448
[19.]
A. Antonelli, C. Ferri, A. Pampana, et al.
Thyroid disorders in chronic hepatitis C.
Am J Med, 117 (2004), pp. 10-13
[20.]
L. Muratori, D.P. Bogdanos, P. Muratori, et al.
Susceptibility to thyroid disorders in hepatitis C.
Clin Gastroenterol Hepatol, 3 (2005), pp. 595-603
[21.]
D.V. Stefanova-Petrova, A.H. Tzvetanska, E.J. Naumova, et al.
Chronic hepatitis C virus infection: prevalence of extrahepatic manifestations and association with cryoglobulinemia in Bulgarian patients.
World J Gastroenterol, 13 (2007), pp. 6518-6528
[22.]
J. Matsuda, N. Saitoh, M. Gotoh, et al.
High prevalence of antiphospholipid antibodies and anti-thyroglobulin antibody in patients with hepatitis C virus infection treated with interferon-alpha.
Am J Gastroenterol, 90 (1995), pp. 1138-1141
[23.]
N. Custro, G. Montalto, V. Scafidi, et al.
Prospective study on thyroid autoimmunity and dysfunction related to chronic hepatitis C and interferon therapy.
J Endocrinol Invest, 20 (1997), pp. 374-380
[24.]
J. Boadas, J. Rodríguez-Espinosa, J. Enríquez, et al.
Prevalence of thyroid autoantibodies is not increased in blood donors with hepatitis C virus infection.
J Hepatol, 22 (1995), pp. 611-615
[25.]
L.M. Prentice, D.I. Phillips, D. Sarsero, et al.
Geographical distribution of subclinical autoimmune thyroid disease in Britain: a study using highly sensitive direct assays for autoantibodies to thyroglobulin and thyroid peroxidase.
Acta Endocrinol, 123 (1990), pp. 493-498
[26.]
R. Minelli, L.E. Braverman, T. Giuberti, et al.
Effects of excess iodine administration on thyroid function in euthyroid patients with a previous episode of thyroid dysfunction induced by interferon-alpha treatment.
Clil Endocrinol, 47 (1997), pp. 357-361
[27.]
X. Moncoucy, F. Leymarie, B. Delemer, et al.
Risk factors and long-term course of thyroid dysfunction during antiviral treatments in 221 patients with chronic hepatitis C.
Gastroenterol Clin Biolog, 29 (2005), pp. 339-345
[28.]
M.C. Hsieh, M.L. Yu, W.L. Chuang, et al.
Virologic factors related to interferon-alpha-induced thyroid dysfunction in patients with chronic hepatitis C.
Eur J Endocrinol, 142 (2000), pp. 431-437
[29.]
M. Lisker-Melman, A.M. Di Bisceglie, S.J. Usala, et al.
Development of thyroid disease during therapy of chronic viral hepatitis with interferon alfa.
Gastroenterol, 102 (1992), pp. 2155-2160
[30.]
J. Primo, J. Hinojosu, J.R. Molés, et al.
Development of thyroid dysfunction after alpha-interferon treatment of chronic hepatitis C.
Am J Gastroenterol, 88 (1993), pp. 1976-1977
[31.]
I. Reid, I. Sharpe, J. McDevitt, et al.
Thyroid dysfunction can predict response to immunotherapy with interleukin-2 and interferon-2 alpha.
Brit J Cancer, 64 (1991), pp. 915-918
[32.]
U. Watanabe, E. Hashimoto, T. Hisamitsu, et al.
The risk factor for development of thyroid disease during interferon-alpha therapy for chronic hepatitis C.
Am J Gastroenterol, 89 (1994), pp. 399-403
[33.]
M.P. Vanderpump, W.M. Tunbridge, J.M. French, et al.
The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey.
Clin Endocrinol, 43 (1995), pp. 55-68
[34.]
J.F. Huang, W.L. Chuang, C.Y. Dai, et al.
The role of thyroid autoantibodies in the development of thyroid dysfunction in Taiwanese chronic hepatitis C patients with interferon-alpha and ribavirin combination therapy.
J Vir Hepat, 13 (2006), pp. 396-401
[35.]
C.J. Grossman, G.A. Roselle, C.L. Mendenhall.
Sex steroid regulation of autoimmunity.
J Ster Biochem Mol Biol, 40 (1991), pp. 649-659
[36.]
Y. Tomer, T.F. Davies.
Searching for the autoimmune thyroid disease susceptibility genes: from gene mapping to gene function.
Endocr Rev, 24 (2003), pp. 694-717
[37.]
C. Carella, G. Amato, B. Biondi, et al.
Longitudinal study of antibodies against thyroid in patients undergoing interferon-alpha therapy for HCV chronic hepatitis.
Horm Res, 44 (1995), pp. 110-114
[38.]
S. Katabami, K. Kamijo, T. Kodama, et al.
An episode of silent thyroiditis in a patient with chronic thyroiditis and papillary adenocarcinoma following alpha interferon treatment for hepatitis C.
Endocr J, 40 (1993), pp. 311-316
[39.]
P. Simmonds.
Genetic diversity and evolution of hepatitis C virus - 15 years on.
J Gen Virol, 85 (2004), pp. 3173-3188
[40.]
H. Gisslinger, B. Gilly, W. Woloszczuk, et al.
Thyroid autoimmunity and hypothyroidism during long-term treatment with recombinant interferon-alpha.
Clil Exp Immunol, 90 (1992), pp. 363-367
[41.]
Y. Nagayama, K. Ohta, M. Tsuruta, et al.
Exacerbation of thyroid autoimmunity by interferon alpha treatment in patients with chronic viral hepatitis: our studies and review of the literature.
Endocr J, 41 (1994), pp. 565-572
[42.]
Y.H. Chung, Y.K. Shong.
Development of thyroid autoimmunity after administration of recombinant human interferonalpha 2b for chronic viral hepatitis.
Am J Gastroenterol, 88 (1993), pp. 244-247
[43.]
K. Yamazaki, Y. Kanaji, K. Shizume, et al.
Reversible inhibition by interferons alpha and beta of 125I incorporation and thyroid hormone release by human thyroid follicles in vitro.
J Clin Endocrinol Metab, 77 (1993), pp. 1439-1441
[44.]
J.G. Hollowell, N.W. Staehling, W.D. Flanders, et al.
Serum TSHm T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III).
J Clin Endocrinol Metab, 87 (2002), pp. 489-499
[45.]
A.P. Weetman, R.C. Smallridge, T.B. Nutman, et al.
Persistent thyroid autoimmunity after subacute thyroiditis.
J Clin Lab Immunol, 23 (1987), pp. 1-6
[46.]
R. Paraná, M. Cruz, L. Lyra, T. Cruz.
Subacute thyroiditis during treatment with combination therapy (interferon plus ribavirin) for hepatitis C virus.
J Vir Hepat, 7 (2000), pp. 393-395
Copyright © 2011. Elsevier Editora Ltda.. All rights reserved
