Impacts of pegylated interferon-ribavirin combination treatment on thyroid functions and thyroid autoimmunity in patients with chronic hepatitis C

Öz

Objectives: Hepatitis C and interferon may trigger autoimmunity. We aimed to investigate the effects of combination treatment of peginterferon alpha (peg-IFN) + ribavirin in patients with chronic hepatitis C (CHC) on thyroid function tests and thyroid auto antibodies. Materials and Methods: The study included 45 outpatients with proven CHC having normal thyroid functions and previously not treated. The patients received combination of Peg-IFN+ribavirin. Values of fT3, fT4, TSH, antitiroglobulin (Anti-Tg) and thyroid peroxidase antibody (Anti-TPO) were measured at initial, fi rst, third and sixth months of treatment. Frequency of thyroid dysfunction was evaluated according to age and gender of patients. Results: Thyroid dysfunction emerged in 15 (%33.3) of 45 patients at the end of the six month of antiviral treatment. Symptomatic thyroid disease was confi rmed in 2 patients.Subclinical hyperthyroidism was determined in four patients (%8.9), and subclinical hypothyroidism in 3 patients (%6.7) at the end of third month.At the end of sixth month; symptomatic hyperthyroidism was observed in one patient (%2.2), subclinical hyperthyroidism in six (%13.3) and subclinical hypothyroidism in 7 patients (%15.6), and symptomatic hypothyroidism was determined in one patient (%2.2).At the end of the sixth month of antiviral treatment; Anti-Tg antibodies were positive in 12 patients (%26.7) and antiTPO in 11 patients (4 male and 7 female) (%24.5). No sig- nifi cant relationship was found between thyroid dysfunction and age, gender and ALT levels of patients (p>0.05). Conclusion: Periodic follow-up examinations should be done for thyroid autoimmunity and thyroid functions in CHC patients receiving combination treatment of PegINF+ribavirin.

Anahtar Kelimeler

• Hepatitis C, peg-interferon, ribavirin, antitiroglobulin, thyroid peroxidase antibodies, autoimmunity

Impacts of pegylated interferon-ribavirin combination treatment on thyroid functions and thyroid autoimmunity in patients with chronic hepatitis C

Öz

Amaç: Hepatit C virusu ve interferon hastalarda otoimmuniteyi tetikleyebilir. Kronik hepatit-C (KCH) hastalarında peginterferon alfa (Peg İFN-α) + ribavirin kombinasyon tedavisinin tiroid fonksiyon testleri ve tiroid otoantikorları uzerine olan etkilerini arastırmayı amacladık. Gereç ve yöntem: Calısma grubu KCH kanıtlanmıs, daha once tedavi edilmemis, tiroid fonksiyonları baslangıcta normal ve tiroid otoantikorları negatif olan 45 hastadan olusturuldu. Tum hastalar peg-IFN+ ribavirin kombinasyonu ile tedavi edildi. Tedavi baslangıcında ve tedavinin 1., 3., ve 6.aylarında butun hastalarda serbest triiodotironin (sT3), serbest tiroksin (sT4), tiroid stimulan hormon (TSH) , antitiroglobulin (Anti-Tg), tiroid peroksidaz otoantikoru (Anti-TPO)değerleri olculdu. Tiroid disfonksiyonu gorulme sıklığı, yas ve cinsiyete gore değerlendirildi. Bulgular: Toplam 45 hastadan 15\'inde (%33.3) altı aylık antiviral tedavi sonunda tiroid disfonksiyonu gelisti ve iki hastada semptomatik tiroid hastalığı goruldu. Bir aylık tedavi sonunda 2 hastada subklinik hipotiroidi goruldu. Uc aylık tedavi sonunda 4 hastada subklinik hipertiroidi (%8.9), 3 hastada (%6.7) subklinik hipotiroidi gozlemlendi. Altı aylık tedavi sonunda ise toplam bir hastada semptomatik hipertiroidi (%2.2), 6 hastada subklinik hipertiroidi (%13.3), 7 hastada subklinik hipotiroidi (%15.6), bir hastada ise semptomatik hipotiroidi (%2.2) goruldu. Oniki hastada (%26.7) 6 aylık antiviral tedavi sonunda antitiroglobulin (anti-Tg)otoantikorları pozitifl esti. Onbir hastada (4 erkek, 7 kadın) (%24.5) 6 aylık antiviral tedavi sonunda tiroid peroksidaz otoantikorları (anti-TPO) pozitifl esti. Tiroid disfonksiyonu ile yas, cinsiyet ve ALT aktivitesi arasında anlamlı bir iliski bulunmadı (p > 0.05). Sonuç: Peg-IFN alfa 2a veya 2b + ribavirin kombinasyon tedavisi alan KCH hastalarının tiroid otoimmunitesi acısından belirli periyotlarla izlenmesi ve otoantikorları pozitifl esen hastalar tiroid disfonksiyonu acısından takip edilmelidir.

Anahtar Kelimeler

• hepatit C, peg-interferon, ribavirin, antitiroglobulin, tiroid peroksidaz otoantikorları, otoimmunite

Kaynakça

1. Branch AD, Seef LB. Hepatitis C: State of the art the mille- nium (oart1). Semin Liver Dis 2000; 20 iii:456-61.
2. Cottler SJ, Komanduri S. Hepatitis C. Clin Persp Gastroen- terol 2002;5:91-9.
3. Poynard T, Mercellin P, Lee SS, et al. Randomised trial of interferon alfa 2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alfa 2b plus placebo for 48 weeks for treatment of chronic with hepatitis C virus. Lancet 1998;352:1426-32.
4. McHutchison JG, Gordon SC, Schiff ER, et al. Interferon alfa 2b alone or in combinationwith ribavirin as initial treatment for chronic hepatitis C. N Eng Med 1998;339:1485-92.
5. Neumann AU, Lam NP,Dahari H, et al.Hepatitis C viral dy- namics in vivo and the antiviral efŞ cacy of interferon alfa therapy. Science 1998; 282:103-7
6. Gale MS, Korth MJ, Tang NM, et al. Evidence that hepatitis C virus resistance to interferon is mediated through repres- sion of the PKR protein kinase by the nonstructural %5 a protein. Virology 1997; 230:217-27.
7. Koh LK, Greenspan FS, YEO PP. Interfron-alfa induced thy- roid dysfunction: three clinical presentations and a review of the literature. Thyroid 1997;7:891-6.
8. Kakzaki S, Takagi H, Murakami M, Takayama H, Mori M. HLA antigens in patients with interferon-alfa induced auto- immune thyroid disorders in chronic hepatitis C. J Hepatol 1999;30:794-800.

9. Ming-Chia H, Ming-Lung Y, Wang-long C, et al. Virologic factors related to interferon alfa induced thyroid dysfunc- tion in patients with chronic hepatitis. CJE Endocrinol 2000;142:431-7.
10. Morisco F, Mazziotti G, Rotondi M, et al. Interferon related thyroid autoimmunity and long term clinical outcome of chronic hepatitis C. Digest Liver Dis 2001; 33:247-53.
11. Mazziotti G, Sorvillo F, Stornaiuolo G, et al. Temporal re- lationship beetween the apperance of thyroid autoantibod- ies and devolopment of destrüctive thyroiditis in patients undergoing treatment with two different type-1 interferons for HCV related chronic hepatitis: a prospective study. J Endocrinol Invest. 2002;25:624-30.
12. Wieslaw Kryczka E, Brojer A, Kowalska A. Thyroid gland dysfunctions during antiviral therapy of chronic hepatitis C. Med Sci Monit 2001;7:221-5.
13. Vial T, Descotes J. Immune-mediated side effects of cytok- ines humans. Toxicology 1995;105:31-57.
14. Kakizaki S, Takagi H, Murakami M, et al. HLA antigens in patients with interferon alfa induced autoimmune thy- roid disorders in chronic hepatitis C. J Hepatol 1999;3:794- 800.
15. Koh L, Greenspan FS, Yeo PPB. Interferon alfa induced thyroid dysfunction: three clinical presentations and a re- view of the literature. Thyroid 1997;7:891-6.
16. Marazuela M, Garcia-Buey L, Gonzales-Fernandez B, et al. Thyroid autoimmune disorders in patients with chronic hepatitis C before and during interferon alfa therapy. Clin Endocrinol 1996;44:635-42.
17. Carella C, Amato G, Biondi B, et al. Longitudinal study of antibodies against thyroid in patients undergoing interferon alfa therapy for HCV chronic hepatitis. Horm Res 1995; 44:110-4.
18. Deutsch M, Dourakis S, Manesis EK, et al. Thyroid abnor- malities in chronic viral hepatitis and their relation ship to interferon alfa therapy. Hepatology 1997;26:206-10.
19. Shuppert F, Rambusch E, Kirchner H, et al. Patients treated with interferon alfa, interferon beta,interleukin-2 have a different thyroid autoantibody pattern than patients suffer- ing from endogenous autoimmune thyroid disease. Thyroid 1997; 7:837-41.
20. Leblebicioglu H. Kronik hepatit C’de güncel tedavi. Ankem Derg 2006; 20:208-12.
21. Gedik H.,Uludağ A., Yahyaoğlu M., Müderrisoğlu C., Fin- cancı M. Kronik hepatit C tedavisinde ribavirin ile birlikte kullanılmakta olan klasik interferon veya pegile interfero- nun etkinliği ve ilaca bağlı yan etkileri açısından karşılaştı- rılması. Nobel Med 2008;4:19-25