Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ; Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ; Switch Therapeutics, Inc, San Francisco, CA.
Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ; Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ; Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Clin Gastroenterol Hepatol. 2023 Nov;21(12):3060-3069.e8. doi: 10.1016/j.cgh.2023.03.002. Epub 2023 Mar 27.
BACKGROUND & AIMS: Carbamoyl phosphate synthetase 1 (CPS1) is a highly abundant mitochondrial urea cycle enzyme that is expressed primarily in hepatocytes. CPS1 is constitutively and physiologically secreted into bile but is released into the bloodstream upon acute liver injury (ALI). Given its abundance and known short half-life, we tested the hypothesis that it may serve as a prognostic serum biomarker in the setting of acute liver failure (ALF).
CPS1 levels were determined using enzyme-linked immunosorbent assay and immunoblotting of sera collected by the ALF Study Group (ALFSG) from patients with ALI and ALF (103 patients with acetaminophen and 167 non-acetaminophen ALF etiologies). A total of 764 serum samples were examined. The inclusion of CPS1 was compared with the original ALFSG Prognostic Index by area under the receiver operating characteristic curve analysis.
CPS1 values for acetaminophen-related patients were significantly higher than for non-acetaminophen patients (P < .0001). Acetaminophen-related patients who received a liver transplant or died within 21 days of hospitalization exhibited higher CPS1 levels than patients who spontaneously survived (P = .01). Logistic regression and area under the receiver operating characteristic analysis of CPS1 enzyme-linked immunosorbent assay values improved the accuracy of the ALFSG Prognostic Index, which performed better than the Model for End-Stage Liver Disease, in predicting 21-day transplant-free survival for acetaminophen- but not non-acetaminophen-related ALF. An increase of CPS1 but not alanine transaminase or aspartate transaminase, when comparing day 3 with day 1 levels was found in a higher percentage of acetaminophen transplanted/dead patients (P < .05).
Serum CPS1 determination provides a new potential prognostic biomarker to assess patients with acetaminophen-induced ALF.
氨甲酰磷酸合成酶 1（CPS1）是一种高度丰富的线粒体尿素循环酶，主要在肝细胞中表达。CPS1 持续且生理性地分泌到胆汁中，但在急性肝损伤（ALI）时会释放到血液中。鉴于其丰富性和已知的短半衰期，我们检验了这样一个假设，即在急性肝衰竭（ALF）中，它可能作为一种预后血清生物标志物发挥作用。
使用酶联免疫吸附测定法和免疫印迹法测定 ALF 研究组（ALFSG）从 ALI 和 ALF 患者（103 例乙酰氨基酚和 167 例非乙酰氨基酚 ALF 病因）采集的血清中 CPS1 水平。共检查了 764 份血清样本。通过接受者操作特征曲线分析的曲线下面积比较 CPS1 的纳入与原始 ALFSG 预后指数。
与非乙酰氨基酚患者相比，乙酰氨基酚相关患者的 CPS1 值明显更高（P<0.0001）。在住院后 21 天内接受肝移植或死亡的乙酰氨基酚相关患者的 CPS1 水平高于自然存活的患者（P=0.01）。CPS1 酶联免疫吸附测定值的逻辑回归和接受者操作特征分析提高了 ALFSG 预后指数的准确性，该指数在预测乙酰氨基酚而非非乙酰氨基酚相关 ALF 的 21 天无移植生存方面优于终末期肝病模型。与第 1 天相比，在第 3 天发现 CPS1 而不是丙氨酸转氨酶或天冬氨酸转氨酶增加的乙酰氨基酚移植/死亡患者比例更高（P<0.05）。
血清 CPS1 测定为评估乙酰氨基酚诱导的 ALF 患者提供了一种新的潜在预后生物标志物。
