Cullaro Giuseppe, Allegretti Andrew S, Patidar Kavish R, Verna Elizabeth C, Lai Jennifer C
Department of Medicine, University of California-San Francisco, San Francisco, California, USA.
Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Liver Transpl. 2025 Jan 1;31(1):24-31. doi: 10.1097/LVT.0000000000000439. Epub 2024 Jul 24.
Among patients with decompensated cirrhosis, serum creatinine (sCr) is biased by sex, frailty, and hepatic synthetic function, while Cystatin C (cysC) is not. We found that sCr would better associate with waitlist mortality and that the difference between cysC and sCr (cysCsCr diff ) would quantify this bias and be independently associated with outcomes. We measured cysC levels at ambulatory liver transplant visits among 525 consecutive patients seen at our center. We defined the cysCsCr diff as the difference between cysC minus sCr. We compared demographics and clinical characteristics in patients with low, intermediate, and high cysCsCr diff , divided by tertile. We used Cox regression to compare the association between sCr and cysC and waitlist mortality and demonstrate the independent association between cysCsCr diff and waitlist mortality. In Cox regression, cysC was significantly more associated with waitlist mortality than sCr ( p < 0.001). We found that as compared to those with a low cysCsCr diff , those with an intermediate or high cysCsCr diff were more likely to be female, have ascites, have higher frailty, and have higher MELD 3.0 scores ( p < 0.05 for all). Compared to those with a low cysCsCr diff , we found that those in the intermediate and high groups were more likely to die during follow-up (low: 6% vs. intermediate: 8% vs. high: 11%, p = 0.007). We found that after adjusting for the components of the MELD 3.0 score, each 1-point increase in the cysCsCr diff was associated with 1.72× (1.27-2.32) the hazard of waitlist mortality. Our study demonstrates that not only is cysC more associated with waitlist mortality than sCr, but that cysCsCr diff represents a novel independent metric associated with waitlist mortality.
在失代偿期肝硬化患者中，血清肌酐（sCr）受性别、虚弱程度和肝脏合成功能的影响存在偏差，而胱抑素C（cysC）则不受这些因素影响。我们发现，sCr与等待名单上的死亡率关联更强，并且cysC与sCr的差值（cysC - sCr差值）能够量化这种偏差，且与预后独立相关。我们在本中心连续就诊的525例门诊肝移植患者中测量了cysC水平。我们将cysC - sCr差值定义为cysC减去sCr的差值。我们比较了cysC - sCr差值处于低、中、高三个三分位数组患者的人口统计学和临床特征。我们使用Cox回归来比较sCr和cysC与等待名单上死亡率的关联，并证明cysC - sCr差值与等待名单上死亡率的独立关联。在Cox回归中，cysC与等待名单上死亡率的关联显著强于sCr（p < 0.001）。我们发现，与cysC - sCr差值低的患者相比，cysC - sCr差值处于中或高的患者更可能为女性、有腹水、虚弱程度更高且终末期肝病模型（MELD）3.0评分更高（所有p值均< 0.05）。与cysC - sCr差值低的患者相比，我们发现中、高组患者在随访期间死亡的可能性更大（低：6% vs. 中：8% vs. 高：11%，p = 0.007）。我们发现，在对MELD 3.0评分的组成部分进行调整后，cysC - sCr差值每增加1分，与等待名单上死亡风险增加1.72倍（1.27 - 2.32）相关。我们的研究表明，不仅cysC与等待名单上死亡率的关联比sCr更强，而且cysC - sCr差值代表了一种与等待名单上死亡率相关的新的独立指标。
