維生素D缺乏與結核病感染之關聯性: 配對密度病例對照研究

Abstract

背景 維生素 D 是正常的先天性和適應性免疫功能對抗結核分枝桿菌的關鍵調節因子。統合分析證據顯示，維生素 D 缺乏會增加結核病感染風險，但實驗設計的不同，使其結論仍存在爭議。本研究旨在研究維生素 D 缺乏是否與台灣的結核病感染有關，並探討造成結核病感染的潛在危險因素。 方法 本研究是一項在台灣，位於東亞北緯 24度的國家，所進行的性別和年齡匹配的病例對照研究 (1:4)，旨在探索維生素 D 缺乏與非 HIV 的結核病感染患者之間的關係。並用條件式羅吉斯迴歸的方法檢查結核病感染的潛在風險因素。 結果 本研究包括 62 名結核病患者和 248 名對照組病患。總體而言，34.2% (106/310) 的參與者都有維生素 D 缺乏的情形。結核病患者的血漿中平均 25(OH)D 的濃度較對照組顯著為低 (21.25±8.93 ng/ml vs 24.45±8.36 ng/ml，p=0.008)。單變量分析發現，較低的身體質量指數（22.9±3.3 kg/m2 vs 25.2±3.9 kg/m2, P<0.001），吸煙者（n=22, 35.5% vs n=43, 17.3%, p=0.002）, 有使用酒精濫用的行為 (n=3, 4.8% vs n=1, 0.4%, p=0.026) 和維生素 D不足20 ng/ml（n=32, 51.6% vs n=74, 29.8%, p=0.001）與對照組相比, 和結核感染有顯著相關;而患有肝硬化病患則有傾向與結核感染有關 (n=3, 4.8% vs n=2, 0.8%, p=0.056)。多變量分析發現，維生素 D 不足20 ng/ml(p=0.002,aOR=3.034 (95%信賴區間為 1.510-6.095)，較低的身體質量指數(p<0.001,aOR=0.805 (95%信賴區間為 0.721-0.899) 、 有肝硬化患者(p=0.042,aOR=8.992 (95%信賴區間為1.088-74.344以及吸煙者(p=0.001, aOR=4.516 (95%信賴區間為 1.853-11.002)和與對照組相比，仍然是結核病感染的獨立危險因子。 結論 與對照個體相比，台灣的非HIV結核感染病患者有顯著的維生素 D 缺乏的現象。此外，我們的數據表明，較低的身體質量指數、吸煙者、肝硬化和 25(OH)D < 20 ng/ml 是感染結核病的獨立危險因素。

Background: Vitamin D is an essential modulator for normal innate and adaptive immune function to combat Mycobacterium tuberculosis infection (TB). However, the association between vitamin D deficiency (VDD, i.e., Vitamin D concentration<20 ng/ml) and tuberculosis remain controversial. Previous studies didn’t control known important confounders, such as body-mass index (BMI), smoking, and diabetes mellitus (DM), and yielded highly heterogeneous results. This study aimed to investigate whether VDD is associated with TB in Taiwan and to identify potential risk factors for TB. Methods and Findings: A sex- and age-matched case-control study (1:4) was conducted to explore the association between VDD (<20 ng/ml) and TB among non-HIV patients at a latitude of 24°N in Taiwan. Conditional logistic regression was used to examine potential risk factors. The study included 62 TB patients and 248 controls. Overall, VDD was diagnosed in 34.2% (106/310) of all participants. The mean 25(OH)D level was significantly lower in TB cases compared to control cases (21.25 ± 8.93 ng/ml vs 24.45 ± 8.36 ng/ml, multi-p=0.008, aOR=0.95 [95% CI = 0.91-0.99]). Multivariable analysis found that VDD (p=0.002), lower body mass index (p<0.001), liver cirrhosis (p=0.042), and smoking (p=0.001) were independent risk factors for TB comparing to the control group. The adjusted odds ratio (aOR) and 95% confidence interval (CI) were 3.034 [95% CI= 1.5-6.1], 0.805 [95% CI= 0.7-0.9], 8.992 [95% CI=1.1-74.3], and 4.516 [95% CI=1.9-11], respectively. Conclusions: Vitamin D deficiency is an independent risk factor for incident active TB among non-HIV patients. Randomized controlled trials are warranted to examine whether vitamin D supplementation reduced the risk of incident TB in high-risk patients with vitamin D deficiency.