Okubo Tomomi, Atsukawa Masanori, Tsubota Akihito, Shimada Noritomo, Abe Hiroshi, Yoshizawa Kai, Arai Taeang, Nakagawa Ai, Itokawa Norio, Kondo Chisa, Aizawa Yoshio, Iwakiri Katsuhiko
Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan.
Core Research Facilities for Basic Science, Research Center for Medical Sciences, Jikei University School of Medicine, Tokyo, Japan.
Hepatol Res. 2017 Jun;47(7):641-649. doi: 10.1111/hepr.12784. Epub 2016 Aug 26.
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.
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.
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⁻ , odds ratio = 5.015) and elderly age (>70 years) (P = 1.85 × 10 , 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 ).
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.
尽管使用直接作用抗病毒药物的无干扰素疗法已发展成为慢性丙型肝炎的治疗标准，但耐药相关变异体（RAV）的存在对治疗结果有负面影响。最近，多项研究表明慢性丙型肝炎与血清维生素D水平之间存在关联。然而，丙型肝炎病毒非结构5A（NS5A）区域的RAV与血清维生素D水平之间的关系尚未得到研究。
在一项多中心合作研究纳入的1型慢性丙型肝炎患者中，我们的研究对象包括247例能够检测NS5A区域RAV的患者。这些RAV通过直接测序法进行检测。
患者的中位年龄为70岁（范围24 - 87岁），女性患者有135例（54.7%）。血清25(OH)D3水平的中位数为22 ng/mL（范围6 - 64 ng/mL）。NS5A区域的L31和Y93 RAV分别在3.7%（9/247）和13.4%（33/247）的患者中被检测到。多变量分析确定维生素D缺乏（血清25(OH)D3≤20 ng/mL）（P = 5.91×10⁻ ，比值比 = 5.015）和老年（>70岁）（P = 1.85×10 ，比值比 = 3.364）是与L31和/或Y93 RAV存在相关的独立影响因素。Y93H RAV在25.9%（29/112）的维生素D缺乏患者中被检测到，而在血清25(OH)D3水平>20 ng/mL的患者中有8.9%（12/135）被检测到（P = 4.90×10 ）。
我们发现NS5A区域的RAV与维生素D缺乏和老年相关，这可能对丙型肝炎病毒感染的固有/适应性免疫反应产生负面影响。
