Bhatia Lokpal, Scorletti Eleonora, Curzen Nicholas, Clough Geraldine F, Calder Philip C, Byrne Christopher D
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.
Atherosclerosis. 2016 Mar;246:13-20. doi: 10.1016/j.atherosclerosis.2015.12.028. Epub 2015 Dec 24.
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.
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.
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.
Improvement in two markers of NAFLD severity is independently associated with reduced CIMT progression.
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。
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。
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。
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。
