Thyroid Dysfunction in Chronic Hepatitis C Patients Treated with Direct-Acting Antivirals: A Systematic Review and Meta-Analysis

Context: Chronic hepatitis C virus (HCV) infection is associated with thyroid dysfunction, historically linked to interferon-based therapies. The impact of direct-acting antivirals (DAAs) on thyroid function remains controversial. Objective: To assess the prevalence and evolution of thyroid dysfunction in HCV-infected patients treated with DAAs through a systematic review with quantitative synthesis where feasible. Methods: A comprehensive literature search was conducted in PubMed, Scopus, Web of Science, and LILACS, without language restrictions, from January 2000 through October 2025, using the following terms: ("hepatitis C" OR "HCV") AND ("thyroid disease" OR "hypothyroidism" OR "hyperthyroidism" OR "thyroiditis") AND ("direct-acting antivirals" OR "DAA" OR "sofosbuvir" OR "ledipasvir" OR "daclatasvir" OR "simeprevir" OR "velpatasvir"). A random-effects meta-analysis of baseline prevalence was performed for three studies with complete extractable data (n=13,915); one study was excluded due to methodological overlap and incomplete denominators. Results: Four studies (n = 14,016) met inclusion criteria. Baseline prevalence of thyroid dysfunction ranged from 13.3% to 24.6%. Quantitative synthesis yielded a pooled prevalence estimate of 19.0% (95% CI: 9.6–30.8%), with substantial heterogeneity (I² = 97.1%). DAA-only regimens did not induce new-onset thyroid dysfunction or autoimmunity. Following sustained virologic response (SVR), 54.5–80% of patients with pre-existing thyroid abnormalities demonstrated improvement or normalization of thyroid function. SVR rates exceeded 95%, irrespective of baseline thyroid status. Conclusion: DAAs exhibit an excellent thyroid safety profile. Despite the high baseline prevalence of thyroid dysfunction among HCV-infected individuals, there is no evidence that DAA therapy induces new thyroid abnormalities; rather, functional improvement is frequently observed after virologic cure.