Interferon-related thyroid autoimmunity and long-term clinical outcome of chronic hepatitis C.
BACKGROUND
A high incidence of thyroid autoantibodies and/or disorders was observed in subjects with hepatitis C virus-related chronic hepatitis during interferon-alpha therapy.


OBJECTIVE
To evaluate whether thyroid autoimmunity and dysfunction, induced by interferon-alpha therapy, could be viewed as predictors for treatment response and as valid prognostic markers of liver disease progression.


METHODS
A total of 136 subjects (96 males/40 females; median age 48 years; range 23-64) affected by biopsy-proven chronic hepatitis C (33.1% with compensated liver cirrhosis).


METHODS
All subjects were treated with interferon-alpha therapy at 6 MU 3 times weekly for 12 months and then followed up for an average period of 60 months (range 12-108). Routine laboratory tests, virological assessment, liver ultrasound, thyroid function tests (serum free-triiodothyronine, free-thyroxine, serum thyrotropin), and autoimmunity were performed for all subjects.


RESULTS
Percentage of thyroid autoimmunity and thyroid dysfunction in long-term responders was not significantly different compared to that in non-responders (47.0% and 11.8% vs 35.3% and 5.9%, respectively; non significant). The multivariate model demonstrated that the absence of cirrhosis was the only factor significantly related to successful response to therapy (odds ratio: 14.9; 95% confidence interval: 1.9-115.0 for chronic hepatitis C vs presence of cirrhosis). Moreover, the occurrence of thyroid autoimmunity during interferon therapy was similar both in patients with or without worsening of liver disease (33.3% and 39.8%, respectively; p = not significant). No subject with on-going liver disease developed thyroid dysfunction during treatment, as opposed to the 10/118 (8.4%) with a better course of liver disease; however, this difference was not statistically significant. The multivariate model showed that age was the only covariate significantly associated with unfavourable outcome of liver disease (odds ratio: 18.6; 95% confidence interval: 2.3-151.9, for those over 48 years vs younger patients).


CONCLUSIONS
There is no evidence that the immune mechanism involved in the pathogenesis of thyroid autoimmune phenomena is the same as that regulating the therapeutic clearance of HCV or modulating the unfavourable course of HCV-related chronic hepatitis. However, our study confirmed that liver disease seems to progress more slowly in younger subjects.
Morisco
F
F
Dept. of Food Sciences, Federico II, University of Naples, Portici, Italy.
Mazziotti
G
G
Rotondi
M
M
Tuccillo
C
C
Iasevoli
P
P
Del Buono
A
A
Sorvillo
F
F
Amato
G
G
Marmo
R
R
Caporaso
N
N
Carella
C
C
D000328:Adult; D000704:Analysis of Variance; D001707:Biopsy, Needle; D018450:Disease Progression; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D018937:Hepatitis C Antibodies / Q000032:analysis; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011336:Probability; D011446:Prospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013960:Thyroid Function Tests; D013967:Thyroiditis, Autoimmune / Q000139:chemically induced* / Q000175:diagnosis
D018937:Hepatitis C Antibodies; D016898:Interferon-alpha