From the, Division of Gastroenterology and Hepatology, (JA, BTKV, AAMM), Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
Governor Kremers Centre-Maastricht University Medical Centre, (SR), Maastricht, The Netherlands.
Alcohol Clin Exp Res. 2021 Jan;45(1):25-37. doi: 10.1111/acer.14512. Epub 2020 Dec 25.
Alcohol-related liver disease is the most frequent cause of cirrhosis and a major indication for liver transplantation. Several alcohol use biomarkers have been developed in recent years and are already in use in several centers. However, in patients with liver disease their diagnostic performance might be influenced by altered biomarker formation by hepatic damage, altered excretion by kidney dysfunction and diuretics use, and altered deposition in hair and nails. We systematically reviewed studies on the diagnostic accuracy of biomarkers of alcohol use in patients with liver disease and performed a detailed study quality assessment.
A structured search in PubMed/Medline/Embase databases was performed for relevant studies, published until April 28, 2019. The risk of bias and applicability concerns was assessed according to the adapted quality assessment of diagnostic accuracy studies-2 (QUADAS-2) checklist.
Twelve out of 6,449 studies met inclusion criteria. Urinary ethyl glucuronide and urinary ethyl sulfate showed high sensitivity (70 to 89 and 73 to 82%, respectively) and specificity (93 to 99 and 86 to 89%, respectively) for assessing any amount of alcohol use in the past days. Serum carbohydrate-deficient transferrin showed low sensitivity but higher specificity (40 to 79 and 57 to 99%, respectively) to detect excessive alcohol use in the past weeks. Whole blood phosphatidylethanol showed high sensitivity and specificity (73 to 100 and 90 to 96%, respectively) to detect any amount of alcohol use in the previous weeks. Scalp hair ethyl glucuronide showed high sensitivity (85 to 100%) and specificity (97 to 100%) for detecting chronic excessive alcohol use in the past 3 to 6 months. Main limitations of the current evidence are the lack of an absolute gold standard to assess alcohol use, heterogeneous study populations, and the paucity of studies.
Urinary and scalp hair ethyl glucuronide are currently the most validated alcohol use biomarkers in patients with liver disease with good diagnostic accuracies. Phosphatidylethanol is a highly promising alcohol use biomarker, but so far less validated in liver patients. Alcohol use biomarkers can complement each other regarding diagnostic time window. More validation studies on alcohol use biomarkers in patients with liver disease are needed.
酒精相关性肝病是肝硬化最常见的病因,也是肝移植的主要指征。近年来已经开发出几种酒精使用生物标志物,并已在多个中心使用。然而,在患有肝病的患者中,由于肝损伤导致生物标志物形成改变、肾功能障碍和利尿剂使用导致排泄改变以及毛发和指甲中沉积改变,其诊断性能可能受到影响。我们系统地综述了关于肝病患者中酒精使用生物标志物诊断准确性的研究,并进行了详细的研究质量评估。
在 PubMed/Medline/Embase 数据库中进行了结构化搜索,以查找截至 2019 年 4 月 28 日的相关研究。根据改良的诊断准确性研究质量评估-2(QUADAS-2)检查表评估了偏倚风险和适用性问题。
在 6449 项研究中,有 12 项符合纳入标准。尿液乙基葡萄糖醛酸苷和尿液乙基硫酸盐分别对评估过去几天内任何剂量的酒精使用具有高灵敏度(分别为 70%至 89%和 73%至 82%)和特异性(分别为 93%至 99%和 86%至 89%)。血清糖基转移蛋白对过去几周内过量饮酒的检测具有低灵敏度,但特异性较高(分别为 40%至 79%和 57%至 99%)。全血磷脂酰乙醇胺对检测过去几周内任何剂量的酒精使用具有高灵敏度和特异性(分别为 73%至 100%和 90%至 96%)。头皮毛发乙基葡萄糖醛酸苷对检测过去 3 至 6 个月内慢性过量饮酒具有高灵敏度(85%至 100%)和特异性(97%至 100%)。目前证据的主要局限性是缺乏评估酒精使用的绝对金标准、研究人群异质性以及研究数量少。
尿液和头皮毛发乙基葡萄糖醛酸苷是目前肝病患者中最具验证性的酒精使用生物标志物,具有良好的诊断准确性。磷脂酰乙醇胺是一种很有前途的酒精使用生物标志物,但迄今为止在肝病患者中验证较少。酒精使用生物标志物在诊断时间窗口上可以互补。需要更多关于肝病患者中酒精使用生物标志物的验证研究。