Vela Stacie, Guerra Andre, Farrell Gail, Trivedi Shubham, Chaffin Hally, Rood Christopher, Singh Ravinder, Kostenko Sergiy, Chang Yu-Hui, Snozek Christine, Patel Krutika, Khatua Biswajit, Singh Vijay P
Gastroenterology Section, Carl T. Hayden Veterans Administration Medical Center, Phoenix, Arizona.
Department of Medicine, Mayo Clinic, Scottsdale, Arizona.
Gastroenterology. 2021 Nov;161(5):1513-1525. doi: 10.1053/j.gastro.2021.07.029. Epub 2021 Jul 23.
BACKGROUND & AIMS: The role of fatty acid ethyl esters (FAEEs) during human alcoholic pancreatitis is unknown. We compared FAEEs levels with their nonesterified fatty acids (NEFAs) precursors during alcohol intoxication and clinical alcoholic pancreatitis. The pathophysiology underlying FAEEs increase and their role as diagnostic biomarkers for alcoholic pancreatitis was investigated.
A prospective blinded study compared FAEEs, NEFAs, and ethanol blood levels on hospitalization for alcoholic pancreatitis (n = 31), alcohol intoxication (n = 25), and in normal controls (n = 43). Serum FAEEs were measured at admission for nonalcoholic pancreatitis (n = 75). Mechanistic cell and animal studies were done.
Median FAEEs were similarly elevated during alcohol intoxication (205 nmol/L; 95% confidence interval [CI], 71.8-515 nmol/L, P < .001) and alcoholic pancreatitis (103.1 nmol/L; 95% CI, 53-689 nmol/L, P < .001) vs controls (1.7 nmol/L; 95% CI, 0.02-4.3 nmol/L) or nonalcoholic pancreatitis (8 nmol/L; 95% CI, 1.1-11.5 nmol/L). Alcoholic pancreatitis increased serum NEFAs (1024 ± 710 μmol/L vs 307 ± 185 μmol/L in controls, P < .05). FAEEs comprised 0.1% to 2% of the parent NEFA concentrations. FAEES correlated strongly with NEFAs independent of ethanol levels in alcoholic pancreatitis but not during alcohol intoxication. On receiver operating characteristic curve analysis for diagnosing alcoholic pancreatitis, the area under the curve for serum FAEEs was 0.87 (95% CI, 0.78-0.95, P < .001). In mice and cells, alcohol administration transiently increased all FAEEs. Oleic acid ethyl ester was the only FAEE with a sustained increase up to 24 hours after intraperitoneal oleic acid plus ethanol administration.
The sustained, alcohol-independent, large (20- to 50-fold) increase in circulating FAEEs during alcoholic pancreatitis results from their visceral release and mirrors the 2- to 4-fold increase in parent NEFA. The large areas under the curve of FAEEs on receiver operating characteristic curve analysis supports their role as alcoholic pancreatitis biomarkers.
脂肪酸乙酯（FAEEs）在人类酒精性胰腺炎中的作用尚不清楚。我们比较了酒精中毒和临床酒精性胰腺炎期间FAEEs水平与其非酯化脂肪酸（NEFAs）前体水平。研究了FAEEs升高的病理生理学机制及其作为酒精性胰腺炎诊断生物标志物的作用。
一项前瞻性盲法研究比较了酒精性胰腺炎患者（n = 31）、酒精中毒患者（n = 25）和正常对照组（n = 43）住院时的FAEEs、NEFAs和乙醇血药浓度。对75例非酒精性胰腺炎患者入院时测定血清FAEEs。进行了细胞和动物机制研究。
与对照组（1.7 nmol/L；95%置信区间[CI]，0.02 - 4.3 nmol/L）或非酒精性胰腺炎患者（8 nmol/L；95% CI，1.1 - 11.5 nmol/L）相比，酒精中毒（205 nmol/L；95% CI，71.8 - 515 nmol/L，P <.001）和酒精性胰腺炎（103.1 nmol/L；95% CI，53 - 689 nmol/L，P <.001）期间FAEEs的中位数同样升高。酒精性胰腺炎使血清NEFAs升高（1024 ± 710 μmol/L，对照组为307 ± 185 μmol/L，P <.05）。FAEEs占母体NEFA浓度的0.1%至2%。在酒精性胰腺炎中，FAEES与NEFAs密切相关，不受乙醇水平影响，但在酒精中毒期间并非如此。在诊断酒精性胰腺炎的受试者工作特征曲线分析中，血清FAEEs的曲线下面积为0.87（95% CI，0.78 - 0.95，P <.001）。在小鼠和细胞中，给予酒精可使所有FAEEs短暂升高。腹腔注射油酸加乙醇后，油酸乙酯是唯一一种持续升高至24小时的FAEE。
酒精性胰腺炎期间循环FAEEs持续、不依赖酒精且大幅（20至50倍）升高是由于其从内脏释放，反映了母体NEFA升高2至4倍。受试者工作特征曲线分析中FAEEs的大曲线下面积支持其作为酒精性胰腺炎生物标志物的作用。
