Department of Medicine, Division of Gastroenterology and Center for Liver Investigation Fostering Discovery, University of Washington, Seattle, Washington, USA.
College of Medicine, Ziauddin University, Karachi, Pakistan.
Hepatol Commun. 2023 Feb 20;7(3):e0076. doi: 10.1097/HC9.0000000000000076. eCollection 2023 Mar 1.
Copper is an essential trace metal serving as a cofactor in innate immunity, metabolism, and iron transport. We hypothesize that copper deficiency may influence survival in patients with cirrhosis through these pathways.
We performed a retrospective cohort study involving 183 consecutive patients with cirrhosis or portal hypertension. Copper from blood and liver tissues was measured using inductively coupled plasma mass spectrometry. Polar metabolites were measured using nuclear magnetic resonance spectroscopy. Copper deficiency was defined by serum or plasma copper below 80 µg/dL for women or 70 µg/dL for men.
The prevalence of copper deficiency was 17% (N=31). Copper deficiency was associated with younger age, race, zinc and selenium deficiency, and higher infection rates (42% vs. 20%, p=0.01). Serum copper correlated positively with albumin, ceruloplasmin, hepatic copper, and negatively with IL-1β. Levels of polar metabolites involved in amino acids catabolism, mitochondrial transport of fatty acids, and gut microbial metabolism differed significantly according to copper deficiency status. During a median follow-up of 396 days, mortality was 22.6% in patients with copper deficiency compared with 10.5% in patients without. Liver transplantation rates were similar (32% vs. 30%). Cause-specific competing risk analysis showed that copper deficiency was associated with a significantly higher risk of death before transplantation after adjusting for age, sex, MELD-Na, and Karnofsky score (HR: 3.40, 95% CI, 1.18-9.82, p=0.023).
In advanced cirrhosis, copper deficiency is relatively common and is associated with an increased infection risk, a distinctive metabolic profile, and an increased risk of death before transplantation.
铜是一种必需的微量元素，作为先天免疫、代谢和铁转运的辅助因子。我们假设铜缺乏可能通过这些途径影响肝硬化患者的生存。
我们进行了一项回顾性队列研究，纳入了 183 例连续的肝硬化或门静脉高压患者。使用电感耦合等离子体质谱法测量血液和肝脏组织中的铜。使用核磁共振波谱法测量极性代谢物。血清或血浆铜低于女性 80μg/dL 或男性 70μg/dL 定义为铜缺乏。
铜缺乏的患病率为 17%（N=31）。铜缺乏与年龄较小、种族、锌和硒缺乏以及更高的感染率有关（42%比 20%，p=0.01）。血清铜与白蛋白、铜蓝蛋白、肝铜呈正相关，与 IL-1β呈负相关。参与氨基酸分解代谢、脂肪酸线粒体转运和肠道微生物代谢的极性代谢物水平根据铜缺乏状态有显著差异。在中位随访 396 天期间，铜缺乏患者的死亡率为 22.6%，而无铜缺乏患者的死亡率为 10.5%。肝移植率相似（32%比 30%）。特异性竞争风险分析显示，在校正年龄、性别、MELD-Na 和卡诺夫斯基评分后，铜缺乏与移植前死亡风险显著增加相关（HR：3.40，95%CI，1.18-9.82，p=0.023）。
在晚期肝硬化中，铜缺乏相对常见，与感染风险增加、独特的代谢谱以及移植前死亡风险增加有关。
