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Thyroid Cancer in Patients With Hepatitis C Infection
To the Editor: Hepatitis C virus (HCV) is the most frequent etiologic factor for non-A and non-B chronic hepatitis worldwide; moreover, a constellation of extrahepatic manifestations has been described in individuals infected with HCV.1 Because of its lymphotropism,2 HCV can represent a chronic stimulus for the immune system leading to a variety of autoimmune and lymphoproliferative disorders such as mixed cryoglobulinemia, membranoproliferative glomerulonephritis, B-cell lymphomas, and autoimmune thyroiditis.1, 3-5 Thyroiditis is frequently found in patients with type C chronic hepatitis during interferon therapy.5 Moreover, thyroiditis can be regarded as preneoplastic condition.6 We report the prevalence of thyroid cancer in a series of patients with chronic hepatitis C infection.
Methods.
A total of 139 patients (76 women and 63 men; mean (SD) age, 52 (14) years with positive serum anti-HCV and HCV RNA titers were consecutively investigated for thyroid involvement. The results were compared with a control group of 835 individuals (501 women and 334 men; mean [SD] age, 48 [16] years) who were recruited during an epidemiological population-based study of the prevalence of thyroid disorders in a light iodine deficiency area from northwest Tuscany. The prevalence of HCV infection in these subjects (0.9%) was comparable with that found in the general Italian population (1.6%). In both groups, fine needle aspiration biopsy was performed in patients with palpable thyroid nodules.
Results.
Among 29 patients with HCV and palpable thyroid nodules, fine needle aspiration biopsy revealed papillary thyroid cancer in 3 patients; 2 of them had been previously treated with interferon alpha (all females, 40, 50 and 65 years). Diagnosis of papillary thyroid cancer was confirmed by histological examination after thyroidectomy. Among 147 subjects with palpable thyroid nodules and no evidence of HCV infection from the control group, fine needle aspiration biopsy findings were negative in all cases. The prevalence of thyroid cancer among patients with HCV infection was significantly higher than among control subjects (Fisher exact test, P=.004), suggesting a possible association of HCV infection in patients with thyroid cancer.
Comment.
An oncogenetic role for HCV has been suggested by several clinicoepidemiological studies examining the prevalence of hepatocellular carcinoma or B-cell non-Hodgkin lymphomas in individuals infected with HCV.1, 3-4,6 Since HCV is an RNA virus that cannot be integrated in the host genome, it can exert its oncogenetic potential through indirect mechanisms with the possible contribution of genetic or environmental factors. The HCV, with and without cirrhosis, represents the most frequent condition predisposing to hepatocellular carcinoma.6 A comparable oncogenetic process could be hypothesized for papillary thyroid cancer complicating thyroid involvement in individuals with HCV-positive test results. If confirmed by further clinico-epidemiological studies, thyroid cancer should be included among harmful complications of chronic HCV infection.
Alessandro Antonelli, MD;
Clodoveo Ferri, MD;
Poupak Fallahi, MD
University of Pisa
Pisa, Italy
1. Gumber S, Chopra S. Hepatitis C: a multifaceted disease; review of extrahepatic manifestations. Ann Intern Med. 1995;123:615-620.
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2. Ferri C, Monti M, La Civita L, et al. Infection of peripheral blood mononuclear cells by hepatitis C virus in mixed cryoglobulinemia. Blood. 1993;82:3701-3704.
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3. Ferri C, La Civita L, Caracciolo F, Zignego AL. Non-Hodgkin's lymphoma: possible role of hepatitis C virus [letter]. JAMA. 1994;272:355-356.
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4. Ferri C, La Civita L, Zignego AL, Pasero G. Viruses and cancers: possible role of hepatitis C virus. Eur J Clin Invest. 1997;27:711-718.
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5. Fernandez-Soto L, Gonzales A, Escobar-Jimenez F, et al. Increased risk of autoimmune thyroid disease in hepatitis C vs hepatitis B before, during, and after discontinuing interferon therapy. Arch Intern Med. 1998;158:1445-1448.
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6. Okayasu I, Fujiwara M, Hara Y, Tanaka Y, Rose NR. Association of chronic lymphocytic thyroiditis and thyroid papillary carcinoma: a study of surgical cases among Japanese, and white and African Americans. Cancer. 1995;76:2313-2318.
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Edited by Margaret A. Winker, MD, Deputy Editor, and Phil B. Fontanarosa, MD, Interim Coeditor.
JAMA. 1999;281:1588.
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