Association between vitamin D deficiency and pre‐existing resistance‐associated hepatitis C virus NS5A variants

Aim Although interferon‐free therapy with direct‐acting antivirals has developed as a standard of care for chronic hepatitis C, the existence of resistance‐associated variants (RAVs) has a negative impact on treatment results. Recently, several studies indicated a relationship between chronic hepatitis C and serum vitamin D levels. However, the relationship between RAVs at the hepatitis C virus non‐structure 5A (NS5A) region and serum vitamin D level has not yet been examined. Methods Among patients with genotype 1 chronic hepatitis C who were enrolled in a multicenter cooperative study, our subjects comprised 247 patients in whom it was possible to measure RAVs at the NS5A region. These RAVs were measured using a direct sequencing method. Results The median age of patients was 70 years (range, 24–87 years), and the number of female patients was 135 (54.7%). The median serum 25(OH) D3 level was 22 ng/mL (range, 6–64 ng/mL). L31 and Y93 RAVs at the NS5A region were detected in 3.7% (9/247) and 13.4% (33/247) of patients, respectively. Multivariate analysis identified vitamin D deficiency (serum 25(OH) D3 ≤ 20 ng/mL) ( P  = 5.91 × 10⁻ 5 , odds ratio = 5.015) and elderly age (>70 years) ( P  = 1.85 × 10 −3 , odds ratio = 3.364) as contributing independent factors associated with the presence of the L31 and/or Y93 RAVs. The Y93H RAV was detected in 25.9% (29/112) of patients with a vitamin D deficiency, and in 8.9% (12/135) of those with a serum 25(OH) D3 level >20 ng/mL ( P  = 4.90 × 10 −3 ). Conclusion We showed that RAVs at the NS5A region are associated with vitamin D deficiency and elderly age, which may have a negative influence on innate/adaptive immune responses to hepatitis C virus infection.