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

作者：Okubo Tomomi; Atsukawa Masanori; Tsubota Akihito; Shimada Noritomo; Abe Hiroshi; Yoshizawa Kai; Arai Taeang; Nakagawa Ai; Itokawa Norio; Kondo Chisa; Aizawa Yoshio; Iwakiri Katsuhiko

来源：Hepatology Research, 2017, 47(7): 641-649.

DOI：10.1111/hepr.12784

• chronic hepatitis C
• NS5A
• resistance-associated variants
• Vitamin D

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, 2487 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 x 10(5), odds ratio = 5.015) and elderly age (>70 years) (P = 1.85x10(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 x 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.

• 出版日期2017-6