Department of Internal Medicine, Virginia Commonwealth University, 1250 E Marshall St, Richmond, Richmond, VA, 23298, USA.
Department of Internal Medicine, Eastern Virginia Medical School, 825 Fairfax Avenue, Norfolk, VA, 23507, USA.
Clin Exp Med. 2022 Feb;22(1):75-81. doi: 10.1007/s10238-021-00733-9. Epub 2021 Jul 8.
Interpreting levels of liver enzymes is often challenging because they may be influenced by metabolic processes beyond the liver. Given their pathophysiologic roles in inflammation and oxidative stress, higher levels of these enzymes may be associated with increased risk of mortality. However, studies have found inconsistent results. Thus, we examined the association of liver enzymes levels with cancer mortality in the general US adult population. We used the US National Health and Nutrition Examination Survey from 1999 to 2016. Kaplan-Meier survival curve comparisons were examined across quartiles of liver enzymes. Cox proportional hazards models were built to examine the relationship between cancer mortality and liver enzymes quartiles without and with adjustment for potential confounding factors. During the 338,882 person-years follow-up, 1059 participants had cancer-related deaths. There was a nonlinear U-shaped relationship between serum alanine and aspartate aminotransferase (ALT and AST) levels and cancer mortality. There was no relationship between cancer mortality and gamma-glutamyltransferase (GGT); however, each 10 IU/L increase in GGT after median was associated with 1% higher mortality risk (HR = 1.01; 95% CI = 1.00, 1.02; P = 0.001). Only subjects with high levels of alkaline phosphatase (ALP) had higher cancer mortality (HR = 1.63; 95CI = 1.30, 2.05; P < 0.001 and HR = 1.52; 95%CI = 1.20, 1.94; P = 0.001, respectively). Only the lowest and highest serum ALT and AST levels are associated with increased cancer mortality. For ALP, the relationship is present at higher levels. The association with GGT was not robust to different analyses. The mechanisms underlying the observed relationships need further exploration.
解读肝酶水平往往具有挑战性，因为它们可能受到肝脏以外的代谢过程的影响。鉴于这些酶在炎症和氧化应激中的病理生理作用，较高的酶水平可能与死亡率增加相关。然而，研究结果并不一致。因此，我们在美国普通成年人群中研究了肝酶水平与癌症死亡率之间的关系。我们使用了 1999 年至 2016 年美国国家健康和营养调查的数据。通过 Kaplan-Meier 生存曲线比较，我们检查了肝酶四分位数的分布情况。我们建立了 Cox 比例风险模型，在不调整和调整潜在混杂因素的情况下，研究了癌症死亡率与肝酶四分位数之间的关系。在 338882 人年的随访期间，有 1059 名参与者死于癌症。血清丙氨酸转氨酶（ALT 和 AST）和天冬氨酸转氨酶水平与癌症死亡率之间呈非线性 U 型关系。γ-谷氨酰转移酶（GGT）与癌症死亡率之间没有关系；然而，中位数后 GGT 每增加 10IU/L，死亡率风险增加 1%（HR=1.01；95%CI=1.00，1.02；P=0.001）。只有碱性磷酸酶（ALP）水平较高的受试者癌症死亡率较高（HR=1.63；95%CI=1.30，2.05；P<0.001 和 HR=1.52；95%CI=1.20，1.94；P=0.001）。只有最低和最高血清 ALT 和 AST 水平与癌症死亡率增加相关。对于 ALP，这种关系存在于较高水平。与 GGT 的关系在不同分析中并不稳健。需要进一步探讨观察到的关系背后的机制。
