Virologic factors related to interferon-alpha-induced thyroid dysfunction in patients with chronic hepatitis C.
OBJECTIVE
Hepatitis C virus (HCV), being reported to be associated with a high prevalence of serological markers of autoimmunity in HCV-infected patients, and possibly sharing partial sequences in amino acid segments with thyroid tissue antigens, may be associated with interferon-alpha (IFN-alpha)-induced thyroid dysfunction in chronic hepatitis C patients. We conducted this study to clarify the issue.


METHODS
One hundred and fifty chronic hepatitis C patients with normal baseline thyroid function were treated with IFN-alpha 2a, 2b and n1 (3-6 million Units three times weekly for 24 weeks). Pretreatment sera were tested for HCV genotype and HCV RNA levels. Serum thyrotropin, total thyroxine and free thyroxine index were performed every 4 weeks for 24 weeks followed by every 8 weeks for another 24 weeks.


RESULTS
Twenty-one (14.0%) patients developed early thyroid dysfunction (abnormal thyroid function during the first 3 months of therapy). Female gender, lower HCV RNA levels, IFN-alpha n1 and a lower IFN-alpha dose were significantly associated with early thyroid dysfunction. On multivariate analysis, gender, IFN-alpha preparation and HCV RNA levels were the significant factors associated with early thyroid dysfunction. Seven (4.7%) patients developed thyroid dysfunction during the second 3 months of IFN-alpha therapy. Taken together, 18.7% patients developed thyroid dysfunction. Female, mixed HCV genotype infection and lower HCV RNA levels were significantly associated with thyroid dysfunction. However, only gender remained significantly associated with IFN-alpha-induced thyroid dysfunction in multivariate analysis.


CONCLUSIONS
The virologic features of HCV may be associated with thyroid dysfunction in chronic hepatitis C patients treated with IFN-alpha. Nevertheless, gender still plays the most important role in IFN-alpha-induced thyroid dysfunction.
Hsieh
M C
MC
Department of Internal Medicine, Koahsiung Medical University, Koahsiung, Taiwan, Republic of China.
Yu
M L
ML
Chuang
W L
WL
Shin
S J
SJ
Dai
C Y
CY
Chen
S C
SC
Lin
Z Y
ZY
Hsieh
M Y
MY
Liu
J F
JF
Wang
L Y
LY
Chang
W Y
WY
D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012737:Sex Factors; D013959:Thyroid Diseases / Q000097:blood / Q000139:chemically induced* / Q000821:virology*; D013960:Thyroid Function Tests; D013963:Thyroid Hormones / Q000097:blood*
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D013963:Thyroid Hormones