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

Abstract

Objective: The aim of this study was to investigate whether the addition of ribavirin (RIBA) to interferon-a (IFN-a) therapy increases the risk of developing thyroid autoimmunity and/or dysfunction. Design and Methods: The study group (group A) included 72 patients undergoing treatment with IFN-a (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-a treatment (42 cases). The control group (group B) encompassed 75 age-and sex-matched patients affected by CHC, undergoing treatment with IFN-a 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-a therapy. Results: Thyroid autoimmunity rate (17/72 for group A and 17/75 for group B) as well as antithyroglobulin 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-a þ RIBA was significantly correlated with a long-term remission of CHC. Conclusions: Our study shows that: (i) the addition of ribavirin to IFN-a 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-a alone are protected from the development of thyroid autoimmunity and/or dysfunction in a second course of antiviral treatment with IFN-a þ RIBA; (iii) the development of hypothyroidism in patients with thyroid autoantibodies undergoing treatment with IFN-a þ RIBA is significantly associated with the long-term remission of CHC.

Hepatitis C Virus Infection of a Thyroid Cell Line: Implications for Pathogenesis of Hepatitis C Virus and Thyroiditis

“…Pooling of data from all studies on HCV infection (as measured by either HCV antibodies or RNA) and thyroid autoimmunity has also demonstrated a significant increased risk of thyroiditis in HCV patients (23). Moreover, IFNa-the mainstay of therapy for chronic HCV infection-adds additional risk for thyroiditis (24)(25)(26)(27)(28). These and other complications of IFNa therapy frequently necessitate stopping therapy or reducing the dose, thereby interfering with effective management of chronic HCV infection.…”

The clinical and physiological spectrum of interferon‐alpha induced thyroiditis

“…At the end of therapy there was no significant difference in the development of thyroid autoimmunity between the two groups; 23.6% of the interferonϩribavirin and 22.7% of the interferon alone treated patients developed TAb's. 58 However, there was a significantly higher frequency of autoimmune hypothyroidism in the patients who received interferonϩribavirin. These results may suggest that in patients receiving interferonϩribavirin one should test more closely for the development of clinical disease than in those receiving interferon alone.…”

“…56,57 Moreover, in most studies examining the frequency of thyroid disorders in interferon treated patients with hepatitis C, approximately 10% of the patients had positive TAb's prior to initiation of interferon therapy (Table 2). 13,34,36,37,58 Some of the problems of earlier studies included the use of less sensitive TAb assays and the lack of control for factors, which may affect the development of thyroid autoimmunity, mainly iodine intake. One recent well-controlled study demonstrated both hypothyroidism and thyroid autoimmunity were more common in patients with hepatitis C compared to controls.…”

“…One recent study examined this possibility. 58 In this study, 72 patients infected with HCV who received combination therapy with IFN␣ and ribavirin were compared to 75 patients infected with HCV who were treated with IFN␣ alone. At the end of therapy there was no significant difference in the development of thyroid autoimmunity between the two groups; 23.6% of the interferonϩribavirin and 22.7% of the interferon alone treated patients developed TAb's.…”

Direct antiviral agent treatment of decompensated hepatitis C virus-induced liver cirrhosis

“…However, the newly-developed DAAs grazoprevir and elbasvir are metabolized by the liver and easily administered to patients with renal dysfunction without adjustment of dose [24] . In general, unlike IFN, DAAs can be administered to patients with autoimmune disorders unless RBV, which might affect the immune status, is included in the regimen [33] . Human Immunodeficiency Virus (HIV)/HCV co-infected patients have the same cure rates, of over 90%, with IFN-free DAA combinations.…”