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.
OBJECTIVE
The aim of this study was to investigate whether the addition of ribavirin (RIBA) to interferon-alpha (IFN-alpha) therapy increases the risk of developing thyroid autoimmunity and/or dysfunction.


METHODS
The study group (group A) included 72 patients undergoing treatment with IFN-alpha (3-6 million units three times weekly) plus RIBA (1.0-1.2 g/day) for chronic hepatitis C (CHC), as first line therapy (30 cases) or as a second therapeutic attempt after a previous ineffective IFN-alpha treatment (42 cases). The control group (group B) encompassed 75 age- and sex-matched patients affected by CHC, undergoing treatment with IFN-alpha alone as first line therapy (35 cases) or as a second therapeutic attempt (40 cases). Thyroid autoimmunity and function were retrospectively evaluated on frozen aliquots, drawn before, after 6 months, and at the end of the antiviral treatment. In patients receiving two antiviral treatments (42 cases in group A and 40 cases in group B) thyroid parameters were also assayed on serum samples drawn before and at the end of the first IFN-alpha therapy.


RESULTS
Thyroid autoimmunity rate (17/72 for group A and 17/75 for group B) as well as anti-thyroglobulin antibodies (TgAb) and anti-thyroid peroxidase antibodies (TPOAb) serum levels were comparable between the two groups. Similarly, in patients undergoing two consecutive antiviral treatments (42 cases in group A and 40 cases in group B) the percentage of positivity for thyroid autoantibodies did not change significantly from the first to the second therapeutic schedules in both groups, with no significant increase of median TgAb and TPOAb levels. By the same token, all but one patient negative for thyroid autoantibodies at the end of the first treatment remained so also during the subsequent treatment. In group A patients, the rate of hypothyroidism (11/72) was significantly higher than that observed in group B (3/75). Similarly, in patients undergoing two consecutive antiviral treatments the percentage of hypothyroidism increased significantly from the first to the second therapeutic schedule in group A (from 4.8% to 19.0%; P<0.05) but not in group B (from 4.7% to 7.1%; not significant). In group A, the occurrence of hypothyroidism during treatment with IFN-alpha+RIBA was significantly correlated with a long-term remission of CHC.


CONCLUSIONS
Our study shows that: (i) the addition of ribavirin to IFN-alpha therapy for CHC does not modify the thyroid autoantibody pattern but it is associated with a higher risk of hypothyroidism; (ii) the patients without thyroid autoantibodies at the end of a previous treatment with IFN-alpha alone are protected from the development of thyroid autoimmunity and/or dysfunction in a second course of antiviral treatment with IFN-alpha+RIBA; (iii) the development of hypothyroidism in patients with thyroid autoantibodies undergoing treatment with IFN-alpha+RIBA is significantly associated with the long-term remission of CHC.
Carella
Carlo
C
Department of Clinical and Experimental Medicine F. Magrassi, Second University of Naples, Naples, Italy. carlo.carella@unina2.it
Mazziotti
Gherardo
G
Morisco
Filomena
F
Rotondi
Mario
M
Cioffi
Michele
M
Tuccillo
Concetta
C
Sorvillo
Francesca
F
Caporaso
Nicola
N
Amato
Giovanni
G
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced* / Q000276:immunology; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects*; D012306:Risk; D013961:Thyroid Gland / Q000187:drug effects* / Q000276:immunology; D013963:Thyroid Hormones / Q000097:blood / Q000276:immunology*
D000998:Antiviral Agents; D001323:Autoantibodies; D016898:Interferon-alpha; D013963:Thyroid Hormones; D012254:Ribavirin