Skip to main content
Top
Published in: Hepatology International 3/2012

01-06-2012 | Original Article

Thyroid autoantibodies and dysfunction do not impact the treatment efficacy of peginterferon and ribavirin combination therapy in chronic hepatitis C

Authors: Jee-Fu Huang, Chao-Kuan Huang, Ming-Lung Yu, Chia-Yen Dai, Chung-Feng Huang, Wei-Wen Hung, Ming-Lun Yeh, Meng-Hsuan Hsieh, Jeng-Fu Yang, Ming-Yen Hsieh, Zu-Yau Lin, Shinn-Chern Chen, Shun-Sheng Wu, Wan-Long Chuang

Published in: Hepatology International | Issue 3/2012

Login to get access

Abstract

Aims

Thyroid disorders, such as the emergence of thyroid autoantibodies (TAs) and thyroid dysfunction (TD), are not uncommon in chronic hepatitis C (CHC) patients. The study aimed to investigate the impact of TAs and dysfunction on the treatment response to pegylated interferon-α plus ribavirin (PegIFN/RBV) combination therapy in CHC patients. The association between interleukin-28B (IL-28B) genetic variants and occurrence of TAs and dysfunction was also analyzed.

Methods

A total of 449 treatment-naive Taiwanese CHC patients with euthyroid status were consecutively enrolled. They received PegIFN/RBV combination therapy with current recommendation. TAs, TD, and IL-28B genetic variants were measured before treatment. Monitoring of TD was done at 3-month intervals during treatment, at end of treatment, and at end of follow-up (EOF).

Results

The development of TAs was detected in 42 (9.4%) patients before treatment, and the incidence of TD during or at EOF was 20%. Of 287 patients with IL-28B rs8099917 TT genotype, 29 (10.1%) had TAs before treatment, whereas the patients with other genotypes did not have TAs (P = 0.04). There was no significant difference of TD incidence during treatment or at EOF between the patients with different IL-28B genotypes. There was also no significant difference of sustained virologic response according to the presence of TAs, TD, or different manifestations of TD.

Conclusion

Taiwanese CHC patients with rs8099917 TT genotype had a higher incidence of TAs. The development of TAs and TD did not impact the treatment efficacy of PegIFN/RBV combination therapy.
Literature
1.
go back to reference Chuang WL, Yu ML, Dai CY, Chang WY. Treatment of chronic hepatitis C in southern Taiwan. Intervirology 2006;49:99–106PubMedCrossRef Chuang WL, Yu ML, Dai CY, Chang WY. Treatment of chronic hepatitis C in southern Taiwan. Intervirology 2006;49:99–106PubMedCrossRef
3.
go back to reference Yang JF, Lin CI, Huang JF, et al. Viral hepatitis infections in southern Taiwan: a multicenter community-based study. Kaohsiung J Med Sci 2010;26:461–469PubMedCrossRef Yang JF, Lin CI, Huang JF, et al. Viral hepatitis infections in southern Taiwan: a multicenter community-based study. Kaohsiung J Med Sci 2010;26:461–469PubMedCrossRef
4.
go back to reference McHutchison JG, Gordon SC, Schiff ER, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. New Engl J Med 1998;339:1485–1492PubMedCrossRef McHutchison JG, Gordon SC, Schiff ER, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. New Engl J Med 1998;339:1485–1492PubMedCrossRef
5.
go back to reference Yu ML, Chuang WL. Treatment of chronic hepatitis C in Asia: when East meets West. J Gastroenterol Hepatol 2009;24:336–345PubMedCrossRef Yu ML, Chuang WL. Treatment of chronic hepatitis C in Asia: when East meets West. J Gastroenterol Hepatol 2009;24:336–345PubMedCrossRef
6.
go back to reference Hadziyannis SJ, Sette H Jr, Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004;140:346–355PubMed Hadziyannis SJ, Sette H Jr, Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004;140:346–355PubMed
7.
go back to reference Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001;358:958–965PubMedCrossRef Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001;358:958–965PubMedCrossRef
8.
go back to reference Yu ML, Dai CY, Huang JF, et al. A randomised study of peginterferon and ribavirin for 16 versus 24 weeks in patients with genotype 2 chronic hepatitis C. Gut 2007;56:553–559PubMedCrossRef Yu ML, Dai CY, Huang JF, et al. A randomised study of peginterferon and ribavirin for 16 versus 24 weeks in patients with genotype 2 chronic hepatitis C. Gut 2007;56:553–559PubMedCrossRef
9.
go back to reference Yu ML, Lin SM, Chuang WL, et al. A sustained virological response to interferon or interferon/ribavirin reduces hepatocellular carcinoma and improves survival in chronic hepatitis C: a nationwide, multicentre study in Taiwan. Antivir Ther 2006;11:985–994PubMed Yu ML, Lin SM, Chuang WL, et al. A sustained virological response to interferon or interferon/ribavirin reduces hepatocellular carcinoma and improves survival in chronic hepatitis C: a nationwide, multicentre study in Taiwan. Antivir Ther 2006;11:985–994PubMed
10.
go back to reference Yu ML, Huang CF, Dai CY, Huang JF, Chuang WL. Long-term effects of interferon-based therapy for chronic hepatitis C. Oncology 2007;72:16–23PubMedCrossRef Yu ML, Huang CF, Dai CY, Huang JF, Chuang WL. Long-term effects of interferon-based therapy for chronic hepatitis C. Oncology 2007;72:16–23PubMedCrossRef
11.
go back to reference Huang JF, Yu ML, Lee CM, et al. Sustained virological response to interferon reduces cirrhosis in chronic hepatitis C: a 1,386-patient study from Taiwan. Aliment Pharmacol Ther 2007;25:1029–1037PubMedCrossRef Huang JF, Yu ML, Lee CM, et al. Sustained virological response to interferon reduces cirrhosis in chronic hepatitis C: a 1,386-patient study from Taiwan. Aliment Pharmacol Ther 2007;25:1029–1037PubMedCrossRef
12.
go back to reference Huang JF, Chuang WL, Dai CY, et al. Viral hepatitis and proteinuria in an area endemic for hepatitis B and C infections: another chain of link? J Intern Med 2006;260:255–262PubMedCrossRef Huang JF, Chuang WL, Dai CY, et al. Viral hepatitis and proteinuria in an area endemic for hepatitis B and C infections: another chain of link? J Intern Med 2006;260:255–262PubMedCrossRef
13.
go back to reference Hsieh MY, Dai CY, Lee LP, et al. Antinuclear antibody is associated with a more advanced fibrosis and lower RNA levels of hepatitis C virus in patients with chronic hepatitis C. J Clin Pathol 2008;61:333–337PubMedCrossRef Hsieh MY, Dai CY, Lee LP, et al. Antinuclear antibody is associated with a more advanced fibrosis and lower RNA levels of hepatitis C virus in patients with chronic hepatitis C. J Clin Pathol 2008;61:333–337PubMedCrossRef
14.
go back to reference Huang JF, Chuang WL, Yu ML, et al. Hepatitis C virus infection and metabolic syndrome—a community-based study in an endemic area of Taiwan. Kaohsiung J Med Sci 2009;25:299–305PubMedCrossRef Huang JF, Chuang WL, Yu ML, et al. Hepatitis C virus infection and metabolic syndrome—a community-based study in an endemic area of Taiwan. Kaohsiung J Med Sci 2009;25:299–305PubMedCrossRef
15.
go back to reference Borg FA, Isenberg DA. Syndromes and complications of interferon therapy. Curr Opin Rheumatol 2007;19:61–66PubMedCrossRef Borg FA, Isenberg DA. Syndromes and complications of interferon therapy. Curr Opin Rheumatol 2007;19:61–66PubMedCrossRef
16.
go back to reference Huang JF, Chuang WL, Dai CY, 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 Viral Hepat 2006;13:396–401PubMedCrossRef Huang JF, Chuang WL, Dai CY, 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 Viral Hepat 2006;13:396–401PubMedCrossRef
17.
go back to reference Tran HA, Malcolm Reeves GE, Gibson R, Attia JR. Development of thyroid diseases in the treatment of chronic hepatitis C with alpha-interferon may be a good prognosticator in achieving a sustained virological response: a meta-analysis. J Gastroenterol Hepatol 2009;24:1163–1168PubMedCrossRef Tran HA, Malcolm Reeves GE, Gibson R, Attia JR. Development of thyroid diseases in the treatment of chronic hepatitis C with alpha-interferon may be a good prognosticator in achieving a sustained virological response: a meta-analysis. J Gastroenterol Hepatol 2009;24:1163–1168PubMedCrossRef
18.
go back to reference Hsieh MC, Yu ML, Chuang WL, et al. Virologic factors related to interferon-alpha-induced thyroid dysfunction in patients with chronic hepatitis C. Eur J Endocrinol 2000;142:431–437PubMedCrossRef Hsieh MC, Yu ML, Chuang WL, et al. Virologic factors related to interferon-alpha-induced thyroid dysfunction in patients with chronic hepatitis C. Eur J Endocrinol 2000;142:431–437PubMedCrossRef
19.
go back to reference Jamil KM, Leedman PJ, Kontorinis N, et al. Interferon-induced thyroid dysfunction in chronic hepatitis C. J Gastroenterol Hepatol 2009;24:1017–1023PubMedCrossRef Jamil KM, Leedman PJ, Kontorinis N, et al. Interferon-induced thyroid dysfunction in chronic hepatitis C. J Gastroenterol Hepatol 2009;24:1017–1023PubMedCrossRef
20.
go back to reference Morisco F, Mazziotti G, Rotondi M, et al. Interferon-related thyroid autoimmunity and long-term clinical outcome of chronic hepatitis C. Dig Liver Dis 2001;33:247–253PubMedCrossRef Morisco F, Mazziotti G, Rotondi M, et al. Interferon-related thyroid autoimmunity and long-term clinical outcome of chronic hepatitis C. Dig Liver Dis 2001;33:247–253PubMedCrossRef
21.
go back to reference Tran HA, Attia JR, Jones TL, Batey RG. Pegylated interferon-alpha 2 beta in combination with ribavirin does not aggravate thyroid dysfunction in comparison to regular interferon-alpha 2 beta in a hepatitis C population: meta-analysis. J Gastroenterol Hepatol 2007;22:472–476PubMedCrossRef Tran HA, Attia JR, Jones TL, Batey RG. Pegylated interferon-alpha 2 beta in combination with ribavirin does not aggravate thyroid dysfunction in comparison to regular interferon-alpha 2 beta in a hepatitis C population: meta-analysis. J Gastroenterol Hepatol 2007;22:472–476PubMedCrossRef
22.
go back to reference Kabbaj N, Guedira MM, El Atmani H, et al. Thyroid disorders during interferon alpha therapy in 625 patients with chronic hepatitis C: a prospective cohort study. Ann Endocrinol 2006;67:343–347CrossRef Kabbaj N, Guedira MM, El Atmani H, et al. Thyroid disorders during interferon alpha therapy in 625 patients with chronic hepatitis C: a prospective cohort study. Ann Endocrinol 2006;67:343–347CrossRef
23.
go back to reference Dalgard O, Bjoro K, Hellum K, et al. Thyroid dysfunction during treatment of chronic hepatitis C with interferon alpha: no association with either interferon dosage or efficacy of therapy. J Intern Med 2002;251:400–406PubMedCrossRef Dalgard O, Bjoro K, Hellum K, et al. Thyroid dysfunction during treatment of chronic hepatitis C with interferon alpha: no association with either interferon dosage or efficacy of therapy. J Intern Med 2002;251:400–406PubMedCrossRef
24.
go back to reference Akeno N, Blackard JT, Tomer Y. HCV E2 protein binds directly to thyroid cells and induces IL-8 production: a new mechanism for HCV-induced thyroid autoimmunity. J Autoimmun 2008;31:339–344PubMedCrossRef Akeno N, Blackard JT, Tomer Y. HCV E2 protein binds directly to thyroid cells and induces IL-8 production: a new mechanism for HCV-induced thyroid autoimmunity. J Autoimmun 2008;31:339–344PubMedCrossRef
25.
go back to reference Tanaka Y, Nishida N, Sugiyama M, et al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet 2009;41:1105–1109PubMedCrossRef Tanaka Y, Nishida N, Sugiyama M, et al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet 2009;41:1105–1109PubMedCrossRef
26.
go back to reference Suppiah V, Moldovan M, Ahlenstiel G, et al. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet 2009;41:1100–1104PubMedCrossRef Suppiah V, Moldovan M, Ahlenstiel G, et al. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet 2009;41:1100–1104PubMedCrossRef
27.
go back to reference Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009;461:399–401PubMedCrossRef Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009;461:399–401PubMedCrossRef
28.
go back to reference Yu ML, Huang CF, Huang JF, et al. Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients. Hepatology 2011;53:7–13PubMedCrossRef Yu ML, Huang CF, Huang JF, et al. Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients. Hepatology 2011;53:7–13PubMedCrossRef
29.
go back to reference Okamoto H, Tokita H, Sakamoto M, et al. Characterization of the genomic sequence of type V (or 3a) hepatitis C virus isolates and PCR primers for specific detection. J Gen Virol 1993;74:2385–2390PubMedCrossRef Okamoto H, Tokita H, Sakamoto M, et al. Characterization of the genomic sequence of type V (or 3a) hepatitis C virus isolates and PCR primers for specific detection. J Gen Virol 1993;74:2385–2390PubMedCrossRef
30.
go back to reference Knodell RG, Ishak KG, Black WC, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981;1:431–435PubMedCrossRef Knodell RG, Ishak KG, Black WC, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981;1:431–435PubMedCrossRef
31.
go back to reference The French METAVIR Cooperative Study Group, Bedossa P. Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. Hepatology 1994;20:15–20 The French METAVIR Cooperative Study Group, Bedossa P. Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. Hepatology 1994;20:15–20
32.
go back to reference Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41:1313–1321PubMedCrossRef Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41:1313–1321PubMedCrossRef
33.
go back to reference Thompson AJ, Muir AJ, Sulkowski MS, et al. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology 2010;139:120–129PubMedCrossRef Thompson AJ, Muir AJ, Sulkowski MS, et al. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology 2010;139:120–129PubMedCrossRef
34.
go back to reference Carella C, Mazziotti G, Morisco F, et al. The addition of ribavirin to interferon-alpha therapy in patients with hepatitis C virus-related chronic hepatitis does not modify the thyroid autoantibody pattern but increases the risk of developing hypothyroidism. Eur J Endocrinol 2002;146:743–749PubMedCrossRef Carella C, Mazziotti G, Morisco F, et al. The addition of ribavirin to interferon-alpha therapy in patients with hepatitis C virus-related chronic hepatitis does not modify the thyroid autoantibody pattern but increases the risk of developing hypothyroidism. Eur J Endocrinol 2002;146:743–749PubMedCrossRef
35.
go back to reference Antonelli A, Ferri C, Ferrari SM, Colaci M, Sansonno D, Fallahi P. Endocrine manifestations of hepatitis C virus infection. Nat Clin Pract Endocrinol Metab 2009;5:26–34PubMedCrossRef Antonelli A, Ferri C, Ferrari SM, Colaci M, Sansonno D, Fallahi P. Endocrine manifestations of hepatitis C virus infection. Nat Clin Pract Endocrinol Metab 2009;5:26–34PubMedCrossRef
36.
go back to reference Huang MJ, Tsai SL, Huang BY, Sheen IS, Yeh CT, Liaw YF. Prevalence and significance of thyroid autoantibodies in patients with chronic hepatitis C virus infection: a prospective controlled study. Clin Endocrinol 1999;50:503–509CrossRef Huang MJ, Tsai SL, Huang BY, Sheen IS, Yeh CT, Liaw YF. Prevalence and significance of thyroid autoantibodies in patients with chronic hepatitis C virus infection: a prospective controlled study. Clin Endocrinol 1999;50:503–509CrossRef
37.
go back to reference Bartolome J, Rodriguez-Inigo E, Quadros P, et al. Detection of hepatitis C virus in thyroid tissue from patients with chronic HCV infection. J Med Virol 2008;80:1588–1594PubMedCrossRef Bartolome J, Rodriguez-Inigo E, Quadros P, et al. Detection of hepatitis C virus in thyroid tissue from patients with chronic HCV infection. J Med Virol 2008;80:1588–1594PubMedCrossRef
38.
go back to reference Antonelli A, Ferri C, Ferrari SM, Colaci M, Fallahi P. Immunopathogenesis of HCV-related endocrine manifestations in chronic hepatitis and mixed cryoglobulinemia. Autoimmun Rev 2008;8:18–23PubMedCrossRef Antonelli A, Ferri C, Ferrari SM, Colaci M, Fallahi P. Immunopathogenesis of HCV-related endocrine manifestations in chronic hepatitis and mixed cryoglobulinemia. Autoimmun Rev 2008;8:18–23PubMedCrossRef
39.
go back to reference Mofredj A, Howaizi M, Grasset D, et al. Diabetes mellitus during interferon therapy for chronic viral hepatitis. Dig Dis Sci 2002;47:1649–1654PubMedCrossRef Mofredj A, Howaizi M, Grasset D, et al. Diabetes mellitus during interferon therapy for chronic viral hepatitis. Dig Dis Sci 2002;47:1649–1654PubMedCrossRef
40.
go back to reference Melo FM, Vasconcelos LR, Silva BS, et al. Structural polymorphism of the mannose-binding lectin 2 (MBL2) gene in HCV-infected patients with a serological marker for thyroid autoimmunity. Int J Immunogenet 2009;36:377–381PubMedCrossRef Melo FM, Vasconcelos LR, Silva BS, et al. Structural polymorphism of the mannose-binding lectin 2 (MBL2) gene in HCV-infected patients with a serological marker for thyroid autoimmunity. Int J Immunogenet 2009;36:377–381PubMedCrossRef
41.
go back to reference Kee KM, Lee CM, Wang JH, et al. Thyroid dysfunction in patients with chronic hepatitis C receiving a combined therapy of interferon and ribavirin: incidence, associated factors and prognosis. J Gastroenterol Hepatol 2006;21:319–326PubMed Kee KM, Lee CM, Wang JH, et al. Thyroid dysfunction in patients with chronic hepatitis C receiving a combined therapy of interferon and ribavirin: incidence, associated factors and prognosis. J Gastroenterol Hepatol 2006;21:319–326PubMed
42.
go back to reference Vezali E, Elefsiniotis I, Mihas C, Konstantinou E, Saroglou G. Thyroid dysfunction in patients with chronic hepatitis C: virus- or therapy-related? J Gastroenterol Hepatol 2009;24:1024–1029PubMedCrossRef Vezali E, Elefsiniotis I, Mihas C, Konstantinou E, Saroglou G. Thyroid dysfunction in patients with chronic hepatitis C: virus- or therapy-related? J Gastroenterol Hepatol 2009;24:1024–1029PubMedCrossRef
Metadata
Title
Thyroid autoantibodies and dysfunction do not impact the treatment efficacy of peginterferon and ribavirin combination therapy in chronic hepatitis C
Authors
Jee-Fu Huang
Chao-Kuan Huang
Ming-Lung Yu
Chia-Yen Dai
Chung-Feng Huang
Wei-Wen Hung
Ming-Lun Yeh
Meng-Hsuan Hsieh
Jeng-Fu Yang
Ming-Yen Hsieh
Zu-Yau Lin
Shinn-Chern Chen
Shun-Sheng Wu
Wan-Long Chuang
Publication date
01-06-2012
Publisher
Springer-Verlag
Published in
Hepatology International / Issue 3/2012
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-011-9308-5

Other articles of this Issue 3/2012

Hepatology International 3/2012 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.