维生素 D 缺乏对慢性乙型肝炎患者结局的不良影响。

Adverse effects of vitamin D deficiency on outcomes of patients with chronic hepatitis B.

机构信息

Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.

Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.

出版信息

Clin Gastroenterol Hepatol. 2015 Apr;13(4):783-90.e1. doi: 10.1016/j.cgh.2014.09.050. Epub 2014 Oct 28.

DOI:10.1016/j.cgh.2014.09.050

PMID:25445773

Abstract

BACKGROUND & AIMS: Vitamin D is an immunomodulator that might be involved in the pathogenesis of viral hepatitis. We investigated the effects of vitamin D deficiency on long-term outcomes of patients with chronic hepatitis B (CHB).

METHODS

We performed a prospective cohort study of 426 patients with CHB (65% male; mean age, 41 ± 13 years), who were enrolled from 1997 through 2000. Serum levels of 25-hydroxycholecalciferol (25(OH)D3) were measured on study enrollment (baseline). Patients were followed for 159 ± 46 months until last clinic visit or death; approximately 33% received antiviral therapy during the follow-up period. The primary outcome was a clinical event (hepatocellular carcinoma, complications of cirrhosis, or death).

RESULTS

At baseline, the patients' mean serum level of hepatitis B virus DNA was 5.0 ± 2.1 log10 IU/mL; their mean level of 25(OH)D3 was 24.3 ± 9.4 ng/mL, and 348 patients (82%) had vitamin D deficiency (<32 ng/mL). Serum levels of 25(OH)D3 did not correlate with cirrhosis or viral load. Ninety-seven patients (22.8%) developed clinical events by a mean time of 118 ± 60 months after study enrollment. Patients who developed clinical events had lower baseline serum levels of 25(OH)D3 (23.2 ± 10.4 ng/mL) than patients who did not (28.2 ± 9.3 ng/mL, P < .001). Low baseline serum 25(OH)D3 was an independent factor associated with clinical events after adjustment for sex, age, and cirrhosis. The adjusted hazard ratio of vitamin D deficiency for clinical events was 1.90 (95% confidence interval [CI], 1.06-2.43; P = .04). The 15-year cumulative incidence rate of clinical events among patients with vitamin D deficiency was 25.5% (95% CI, 23.1%-27.9%), compared with 11.1% (95% CI, 7.4%-14.8%) in patients with normal serum levels of 25(OH)D3.

CONCLUSIONS

Vitamin D deficiency is common among patients with CHB and is associated with adverse clinical outcomes.

摘要

背景与目的

维生素 D 是一种免疫调节剂，可能参与了病毒性肝炎的发病机制。我们研究了维生素 D 缺乏对慢性乙型肝炎（CHB）患者长期结局的影响。

方法

我们对 1997 年至 2000 年间入组的 426 例 CHB 患者（男性占 65%；平均年龄 41±13 岁）进行了前瞻性队列研究。在研究入组时（基线）测量了血清 25-羟胆钙化醇（25（OH）D3）水平。患者随访 159±46 个月，直至最后一次就诊或死亡；大约 33%的患者在随访期间接受了抗病毒治疗。主要结局是临床事件（肝细胞癌、肝硬化并发症或死亡）。

结果

基线时，患者血清乙型肝炎病毒 DNA 平均水平为 5.0±2.1 log10 IU/mL；血清 25（OH）D3 平均水平为 24.3±9.4ng/mL，348 例（82%）患者存在维生素 D 缺乏症（＜32ng/mL）。血清 25（OH）D3 水平与肝硬化或病毒载量无关。97 例（22.8%）患者在研究入组后平均 118±60 个月时发生临床事件。发生临床事件的患者基线血清 25（OH）D3 水平较低（23.2±10.4ng/mL），而未发生临床事件的患者基线血清 25（OH）D3 水平较高（28.2±9.3ng/mL，P＜0.001）。经性别、年龄和肝硬化校正后，低基线血清 25（OH）D3 是与临床事件相关的独立因素。维生素 D 缺乏症发生临床事件的调整后危险比为 1.90（95%可信区间[CI]，1.06-2.43；P=0.04）。维生素 D 缺乏症患者的 15 年临床事件累积发生率为 25.5%（95%CI，23.1%-27.9%），而血清 25（OH）D3 水平正常的患者为 11.1%（95%CI，7.4%-14.8%）。