AASLD 2017:范建高教授点评:HepQuant-STAT简易肝功能定量检测对NASH的无创诊断与评估

2017-10-23 佚名 国际肝病

非酒精性脂肪性肝炎(NASH)的诊断金标准为肝脏病理活检,但因其有创性与采样误差而应用受限。第68届美国肝病研究学会(AASLD)年会口头报告平行会上,来自美国的研究团队报道了一种简易肝脏功能定量检测——HepQuant-STAT(HQ-STAT),其可无创诊断非酒精性脂肪性肝炎(NASH),并评估疾病严重程度(摘要号:96)。

非酒精性脂肪性肝炎(NASH)的诊断金标准为肝脏病理活检,但因其有创性与采样误差而应用受限。第68届美国肝病研究学会(AASLD)年会口头报告平行会上,来自美国的研究团队报道了一种简易肝脏功能定量检测——HepQuant-STAT(HQ-STAT),其可无创诊断非酒精性脂肪性肝炎(NASH),并评估疾病严重程度(摘要号:96)。

在此特邀请中华医学会肝病学分会脂肪肝和酒精性肝病学组名誉组长、上海交通大学医学院附属新华医院消化内科范建高教授对该项研究进行点评,为NASH的无创诊断研究指明方向。

研究概述:

该研究纳入了50名健康对照,其中包括30名体重正常(BMI 18.5~25 kg/m2),16名超重(BMI 25~30 kg/m2),以及4名肥胖(BMI>30 kg/m2)的研究对象。而NASH患者包括27名肝活检证实的NASH,以及4名合并肥胖的隐源性肝硬化患者。

根据Brunt-Kleiner肝硬化评分,NASH组纤维化评分F1为4名,F2为4名,F3为5名,F4为18名。其中在18名肝硬化患者中,9名为失代偿肝硬化。除了对纤维化评分的评估,NASH的严重程度亦通过静脉曲张的严重程度进行评估。

HQ-STAT的检测需患者口服40 mg四氘胆酸(d4-CA)后60小时进行抽血,采用液态色谱与质谱联用(LCMS)的方法检测血清学测定d4-CA的浓度,进一步根据体重校正,得到HQ-STAT值。

该研究结果发现,HQ-STAT值>0.5 μM可作为诊断NASH的截断值,即使对照组中存在超重以及肥胖的个体,亦有较好的阴性预测值(NPV=95%)。在NASH组中,HQ-STAT值与NASH的严重程度亦相关:存在静脉曲张STAT截断值为>1.08 μM,肝硬化为STAT值>1.25 μM,而严重静脉曲张STAT截断值>2.4 μM。

其中,对静脉曲张的诊断有较好的阴性预测值(诊断静脉曲张,NPV=88%,严重静脉曲张,NPV=95%);而对肝硬化的诊断具有较好的阳性预测值(PPV=100%)。

总的来说,该研究通过一种简单的测定方法,用几乎无创的手段对NASH进行诊断,且HQ-STAT值亦可用于评估NASH患者有无肝硬化以及严重静脉曲张。

点评:

非酒精性脂肪性肝炎(NASH)的诊断金标准为肝脏病理活检,但因其有创性与采样误差影响应用受限[1],而针对NASH的无创诊断方法的探索对NAFLD病程的评估和干预的选择至关重要。目前围绕NASH的无创诊断指标如细胞角蛋白 18(cyrokeratin-18,CK-18)、铁蛋白等有较好的应用前景,但目前仍欠缺很好的灵敏度与特异度的验证以及其他慢性肝病中的验证。

该研究提出了一种新的NASH无创诊断方案:通过监测口服后四氘胆酸的血清水平并进行校正评估得到HQ-STAT值。其评估方法较为简便,且在研究中随着与肝脏疾病的进展如肝硬化、静脉曲张的出现,HQ-STAT值逐渐升高,其截断值有较好的诊断效力,可能是潜在的肝脏纤维化的无创诊断检测方法。

但该研究亦有一些不足之处:首先,该研究中大部分NASH研究对象存在肝硬化甚至是失代偿肝硬化,而该研究中并未评估其肝脏病理小叶内炎症以及气球样变等指标,且往往进展至肝硬化以及失代偿肝硬化时期已经难以评估其肝脂肪变以及肝细胞炎症的水平,故该指标实际上难以对NASH进行诊断以及对炎症程度进行评估,而对于纤维化的评估亦或有更好的评价效果,进一步实验可与Fibroscan肝硬度测定的诊断效力进行比较。

其次,该研究NASH组的诊断标准均为肝活检证实的NASH患者,而对照组并未肝活检,因此并不能完全排除对照组亦存在脂肪肝以及NASH的情况,可能影响结果的准确性。

除此之外,该研究样本量较小,其中NASH仅有27例,而在NASH组中进一步分为有无肝硬化以及静脉曲张等亚组进行AUROC的分析得截断值,且得到的截断值并未采用新的验证组进行验证,若该检测方法进一步推广,则接下来需在大样本量的临床研究中进行验证该指标的诊断效应。

最后,因该检测方法需口服药物制剂,在该检测模型大规模临床试验前,对该口服制剂存在的药物代谢动力学、毒性以及副反应需进行进一步的挖掘与评估以确保其应用的安全性。

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    2018-09-24 海豹
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    2017-10-25 kksonne
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    2017-10-25 lq1771

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大量的脂肪在肝脏细胞内异常积累,称为非酒精性脂肪性肝病(NAFLD),之所以称为"非酒精性",是为了与酒精性肝病相区别。随着肥胖及其相关代谢综合征全球化的流行趋势,非酒精性脂肪性肝病现已成为欧美等发达国家和我国富裕地区慢性肝病的重要病因,普通成人NAFLD患病率10%~30%,其中10%~20%为NASH,后者10年内肝硬化发生率高达25%。非酒精性脂肪性肝炎(non-alcoholic st

Nat Med:武汉大学李红良教授发现非酒精性脂肪性肝炎(NASH)关键治疗靶点

非酒精性脂肪性肝炎(NASH)是一种进行性疾病,通常伴有代谢综合征,是严重肝损伤的高风险因素。然而,目前没有有效的药物用于NASH的治疗。


最近,武汉大学李红良教授在Nature Medicine上发表文章,成功发现NASH的关键靶点,对NASH的治疗具有重要价值。李红良教授近十余年来一直致力于心血管代谢性疾病的研究,围绕天然免疫调控网络对心血管代谢性疾病的作用,进行了深入的研究与探讨,取得了一系列重要研究成果。去年也成功在Nature Medicine上发表研究成果( · 2017-02-24

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JCEM:胆汁酸与肥胖患者的胰岛素抵抗有关?

胆汁酸(BA)是控制能量动态平衡的信号分子,对肝脏既有毒又有保护作用。已有报道称BA在肥胖、胰岛素抵抗(IR)和非酒精性脂肪性肝炎(NASH)中改变。然而,BA改变是否独立于代谢状态导致NASH尚不清楚。

预防糖尿病有妙招—快速高强度的锻炼

近日,来自昆士兰大学的研究人员通过研究发现,短时间的高强度运动或能帮助非酒精性脂肪肝患者降低患2型糖尿病的风险;文章中研究人员调查了是否高强度间歇训练(High Intensity Interval Training,HIIT)能够改善机体对胰岛素的敏感性、适应性以及其它心血管疾病的风险因

Clin Gastroenterol H:非酒精性脂肪肝肥胖患者接受减肥手术要当心!!!

由此可见,非酒精性脂肪肝炎与接受减肥手术患者的死亡风险增加有关,在非酒精性脂肪肝炎的受试者中进行减肥手术的生存获益可能性减少。