非酒精性脂肪性肝病严重程度的改善与颈动脉内膜中层厚度进展的降低相关。
Improvement in non-alcoholic fatty liver disease severity is associated with a reduction in carotid intima-media thickness progression.
作者信息
Bhatia Lokpal, Scorletti Eleonora, Curzen Nicholas, Clough Geraldine F, Calder Philip C, Byrne Christopher D
机构信息
Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK; Wessex Cardiac Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
出版信息
Atherosclerosis. 2016 Mar;246:13-20. doi: 10.1016/j.atherosclerosis.2015.12.028. Epub 2015 Dec 24.
BACKGROUND AND AIMS
n-3 polyunsaturated fatty acid (PUFA) treatment may decrease liver fat in non-alcoholic fatty liver disease (NAFLD), but uncertainty exists whether this treatment also decreases cardiovascular disease (CVD) risk in NAFLD. We tested whether 15-18 months n-3 PUFA [docosahexaenoic acid (DHA) and eicosapentaenoic acid] (Omacor/Lovaza, 4 g/day) vs placebo decreased carotid intima-media thickness (CIMT) progression, a surrogate marker of CVD risk. We also evaluated if improvement in markers of NAFLD severity was associated with decreased CIMT progression over time.
METHODS
In a pre-specified sub-study of the WELCOME (Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy) trial (NCT00760513), CIMT was measured using B-mode ultrasound while NAFLD severity was assessed by measuring liver fat percentage (magnetic resonance spectroscopy) and hepatic necro-inflammation (serum cytokeratin-18 (CK-18) concentration), at baseline and end of study.
RESULTS
92 patients (age 51.5 ± 10.7 years, 57.6% men) completed the study. In the treatment group (n = 45), CIMT progressed by 0.012 mm (IQR 0.005-0.020 mm) compared to 0.015 mm (IQR 0.007-0.025 mm) in the placebo group (n = 47) (p = 0.17). Reduced CIMT progression in the entire cohort was independently associated with decreased liver fat (standardized β-coefficient 0.32, p = 0.005), reduced CK-18 levels (standardized β-coefficient 0.22, p = 0.04) and antihypertensive usage (standardized β-coefficient -0.31, p = 0.009) in multivariable regression analysis after adjusting for all potential confounders. Decreased weight (standardized β-coefficient 0.30, p < 0.001) and increased DHA tissue enrichment during the 18-month study (standardized β-coefficient -0.19, p = 0.027) were both independently associated with decreased liver fat, but not with CK-18.
CONCLUSION
Improvement in two markers of NAFLD severity is independently associated with reduced CIMT progression.
背景与目的
n-3多不饱和脂肪酸（PUFA）治疗可能会降低非酒精性脂肪性肝病（NAFLD）患者的肝脏脂肪，但该治疗是否也能降低NAFLD患者的心血管疾病（CVD）风险尚不确定。我们测试了15 - 18个月的n-3 PUFA[二十二碳六烯酸（DHA）和二十碳五烯酸]（Omacor/Lovaza，4克/天）与安慰剂相比，是否能降低颈动脉内膜中层厚度（CIMT）进展，CIMT进展是CVD风险的一个替代指标。我们还评估了NAFLD严重程度标志物的改善是否与CIMT随时间的进展降低相关。
方法
在WELCOME（非酒精性脂肪性肝病中使用OMacor治疗对肝脏和心血管标志物的韦塞克斯评估）试验（NCT00760513）的一项预先指定的子研究中，使用B型超声测量CIMT，同时通过测量肝脏脂肪百分比（磁共振波谱法）和肝脏坏死性炎症（血清细胞角蛋白-18（CK-18）浓度）来评估NAFLD严重程度，在基线和研究结束时进行测量。
结果
92名患者（年龄51.5±10.7岁，57.6%为男性）完成了研究。治疗组（n = 45）的CIMT进展了0.012毫米（四分位间距0.005 - 0.020毫米），而安慰剂组（n = 47）为0.015毫米（四分位间距0.007 - 0.025毫米）（p = 0.17）。在调整所有潜在混杂因素后的多变量回归分析中，整个队列中CIMT进展的降低与肝脏脂肪减少（标准化β系数0.32，p = 0.005）、CK-18水平降低（标准化β系数0.22，p = 0.04）和使用降压药（标准化β系数 - 0.31，p = 0.009）独立相关。体重减轻（标准化β系数0.30，p < 0.001）和在18个月研究期间DHA组织富集增加（标准化β系数 - 0.19，p = 0.027）均与肝脏脂肪减少独立相关，但与CK-18无关。
结论
NAFLD严重程度的两个标志物的改善与CIMT进展的降低独立相关。
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