Direct-acting antiviral treatment impact on glycemic control in HCV-infected T2DM patients: An observational study with Mendelian randomization analysis.

Hepatitis C virus (HCV) infection is a major global health issue, associated with various metabolic disorders, including type 2 diabetes mellitus (T2DM). This study explores the impact of direct-acting antiviral agents (DAAs) on diabetes management in patients coinfected with HCV and T2DM. This study comprised a cross-sectional analysis of NHANES database (1999-2018) participants with HCV antibody-positive status and a retrospective cohort of T2DM patients achieving sustained virological response after DAAs treatment at The Fourth Hospital of Huai'an (2020-2023). We conducted Mendelian randomization analysis using expression Quantitative Trait Loci data (eQTLGen, GTEx) and protein quantitative trait loci data (Iceland Protein, UK Biobank) of DAAs target genes from blood and liver samples. The cross-sectional NHANES analysis assessed antiviral therapy effects on diabetes indicators, while the retrospective study evaluated changes in hemoglobin A1c (HbA1c) and fasting glucose at 6, 12, and 18 months post-DAA treatment. Mendelian randomization highlighted the potential role of the CXCL10 gene in modulating HbA1c levels. The cross-sectional NHANES study found no significant associations between interferon/ribavirin use and diabetes indicators. In the retrospective study, significant short-term improvements in HbA1c and fasting glucose were observed within 6 months of DAA therapy; however, these were not sustained over 12 to 18 months. Notably, patients with cirrhosis or abnormal BMI showed no short-term metabolic improvements. The study underscores the transient nature of the metabolic improvements following HCV eradication in T2DM patients and stresses the importance of comprehensive management strategies to sustain glycemic control in the long term.