Department of Medicine, University of California, San Francisco.
Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern Medicine, Chicago, Illinois.
JAMA Surg. 2021 Mar 1;156(3):256-262. doi: 10.1001/jamasurg.2020.5674.
Female liver transplant candidates experience higher rates of wait list mortality than male candidates. Frailty is a critical determinant of mortality in patients with cirrhosis, but how frailty differs between women and men is unknown.
To determine whether frailty is associated with the gap between women and men in mortality among patients with cirrhosis awaiting liver transplantation.
DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study enrolled 1405 adults with cirrhosis awaiting liver transplant without hepatocellular carcinoma seen during 3436 ambulatory clinic visits at 9 US liver transplant centers. Data were collected from January 1, 2012, to October 1, 2019, and analyzed from August 30, 2019, to October 30, 2020.
At outpatient evaluation, the Liver Frailty Index (LFI) score was calculated (grip strength, chair stands, and balance).
The risk of wait list mortality was quantified using Cox proportional hazards regression by frailty. Mediation analysis was used to quantify the contribution of frailty to the gap in wait list mortality between women and men.
Of 1405 participants, 578 (41%) were women and 827 (59%) were men (median age, 58 [interquartile range (IQR), 50-63] years). Women and men had similar median scores on the laboratory-based Model for End-stage Liver Disease incorporating sodium levels (MELDNa) (women, 18 [IQR, 14-23]; men, 18 [IQR, 15-22]), but baseline LFI was higher in women (mean [SD], 4.12 [0.85] vs 4.00 [0.82]; P = .005). Women displayed worse balance of less than 30 seconds (145 [25%] vs 149 [18%]; P = .003), worse sex-adjusted grip (mean [SD], -0.31 [1.08] vs -0.16 [1.08] kg; P = .01), and fewer chair stands per second (median, 0.35 [IQR, 0.23-0.46] vs 0.37 [IQR, 0.25-0.49]; P = .04). In unadjusted mixed-effects models, LFI was 0.15 (95% CI, 0.06-0.23) units higher in women than men (P = .001). After adjustment for other variables associated with frailty, LFI was 0.16 (95% CI, 0.08-0.23) units higher in women than men (P < .001). In unadjusted regression, women experienced a 34% (95% CI, 3%-74%) increased risk of wait list mortality than men (P = .03). Sequential covariable adjustment did not alter the association between sex and wait list mortality; however, adjustment for LFI attenuated the mortality gap between women and men. In mediation analysis, an estimated 13.0% (IQR, 0.5%-132.0%) of the gender gap in wait list mortality was mediated by frailty.
These findings demonstrate that women with cirrhosis display worse frailty scores than men despite similar MELDNa scores. The higher risk of wait list mortality that women experienced appeared to be explained in part by frailty.
女性肝移植候选者的等待名单死亡率高于男性候选者。脆弱性是肝硬化患者死亡的关键决定因素，但女性和男性之间的脆弱性差异尚不清楚。
确定脆弱性是否与肝硬化患者等待肝移植期间女性和男性之间的死亡率差距有关。
设计、地点和参与者：这项前瞻性队列研究纳入了 1405 名没有肝细胞癌的肝硬化患者，他们在 9 家美国肝移植中心的 3436 次门诊就诊期间接受了评估。数据收集于 2012 年 1 月 1 日至 2019 年 10 月 1 日，分析于 2019 年 8 月 30 日至 2020 年 10 月 30 日进行。
在门诊评估时，计算了肝衰竭指数（LFI）评分（握力、椅子站立和平衡）。
使用 Cox 比例风险回归模型定量评估等待名单死亡率的风险，并使用中介分析量化脆弱性对女性和男性等待名单死亡率差距的贡献。
在 1405 名参与者中，578 名（41%）为女性，827 名（59%）为男性（中位年龄，58 [四分位距（IQR），50-63] 岁）。女性和男性的基于实验室的包含钠水平的终末期肝病模型（MELDNa）评分中位数相似（女性，18 [IQR，14-23]；男性，18 [IQR，15-22]），但基线 LFI 更高（均值[标准差]，4.12 [0.85] vs 4.00 [0.82]；P = .005）。女性的平衡较差（<30 秒）的比例较高（145 [25%] vs 149 [18%]；P = .003），调整后的握力较差（均值[标准差]，-0.31 [1.08] vs -0.16 [1.08] kg；P = .01），每秒椅子站立次数较少（中位数，0.35 [IQR，0.23-0.46] vs 0.37 [IQR，0.25-0.49]；P = .04）。在未调整的混合效应模型中，女性的 LFI 比男性高 0.15 个单位（95%CI，0.06-0.23）（P = .001）。在调整了与脆弱性相关的其他变量后，女性的 LFI 比男性高 0.16 个单位（95%CI，0.08-0.23）（P < .001）。在未调整的回归中，女性等待名单死亡率的风险比男性高 34%（95%CI，3%-74%）（P = .03）。连续的协变量调整并没有改变性别与等待名单死亡率之间的关联；然而，调整脆弱性减弱了女性和男性之间的死亡率差距。在中介分析中，估计性别等待名单死亡率差距的 13.0%（IQR，0.5%-132.0%）是由脆弱性介导的。
这些发现表明，尽管 MELDNa 评分相似，但肝硬化女性的脆弱性评分比男性差。女性等待名单死亡率较高的风险似乎部分是由脆弱性引起的。
