Supplementary Material for: Occurrence, characteristics and outcome of hypoxic liver injury among patients aged ≥ 90 years admitted to the intensive care unit – a retrospective cohort study

Introduction: Hypoxic liver injury (HLI) is a frequent and life-threatening complication occurring in up to 10 % of critically ill patients. Heart failure and age were previously identified as risk factors for occurrence of HLI. However, there is a lack of data on incidence of HLI and its clinical implications on outcome in very old (≥ 90 years) patients. The aim of this study was to investigate occurrence, clinical characteristics and outcome of HLI in critically ill patients ≥ 90 years. Methods: Retrospective analysis of all consecutive critically ill patients ≥ 90 years admitted to the intensive care unit (ICU) of a tertiary care university hospital in Hamburg, Germany. Clinical course and laboratory were analysed from all patients. HLI was defined according to established criteria as elevation of aminotransferase levels (> 20-fold upper limit of normal). Predictors of HLI, occurrence, clinical course and outcome were assessed and compared to patients without HLI. Results: In total, 1065 critically ill patients ≥ 90 years were included. During the ICU stay, 3% (n = 35) developed HLI. Main causes of HLI were cardiogenic shock (51%, n = 18), septic shock (23%, n = 8) and cardiac arrest (20%, n = 7). Presenting characteristics including age, gender and BMI were comparable between patients with and without HLI. The admission cause was primary medical (HLI: 49% vs. No-HLI: 34%, p = 0.07), surgical – planned (9% vs. 38%, p < 0.001) and surgical – emergency (43% vs. 28%, p = 0.06). The Charlson Comorbidity Index (CCI) and the updated CCI was median 2 (1 – 3) and 2 (1 – 2) points in patients with and 1 (0 – 2) and 1 (0 – 2) in patients without HLI (p < 0.01 and p = 0.08). Patients with HLI presented with higher SAPS II (55 vs. 36 points p < 0.001) score on admission and required mechanical ventilation (66% vs. 34%, p < 0.001), vasopressor therapy (91% vs. 40%, p < 0.001), renal replacement therapy (20% vs. 2%, p < 0.001) and parenteral nutrition (29% vs. 7%, p < 0.001). The ICU-mortality and hospital mortality in patients with HLI was 66% (n = 23) and 83% (n = 29) compared with 17% (n = 170) and 28% (n = 292) in patients without HLI, respectively (both p < 0.001). Regression analysis identified SAPS II [OR 1.05, 95% CI (1.02 – 1.07); p < 0.001] and vasopressor therapy [OR 9.21, 95% CI (2.58 – 32.86); p < 0.01] as factors significantly associated with new-onset of HLI. Occurrence of HLI was independently associated with mortality [HR 2.23, 95% CI (1.50 – 3.30); p < 0.001]. Discussion/Conclusion: HLI is an uncommon but not rare condition in critically ill patients aged ≥ 90 years. Occurrence of HLI is associated with high mortality and mainly caused by cardiogenic or septic shock. HLI may serve as early prognostic marker in critically ill patients aged ≥ 90 years.

引言：缺氧性肝损伤（Hypoxic liver injury, HLI）是一种常见且致命的并发症，在高达10%的重症患者中发生。既往研究已明确心力衰竭与年龄为HLI发生的危险因素。然而，目前尚缺乏针对极老年（≥90岁）患者的HLI发病率及其对预后临床意义的相关数据。本研究旨在探讨≥90岁重症患者中HLI的发生情况、临床特征与预后。

方法：对德国汉堡某大学附属三级医疗中心重症监护病房（intensive care unit, ICU）连续收治的≥90岁重症患者进行回顾性分析。收集所有患者的临床病程与实验室检查数据。HLI的定义参照公认标准：氨基转移酶水平升高至正常上限的20倍以上。评估HLI的预测因素、发生情况、临床病程与预后，并与无HLI患者进行对比。

结果：本研究共纳入1065例≥90岁的重症患者。在ICU住院期间，共有3%（n=35）的患者发生HLI。HLI的主要病因包括心源性休克（51%，n=18）、感染性休克（23%，n=8）与心脏骤停（20%，n=7）。HLI组与非HLI组患者的基线特征（包括年龄、性别与体质量指数（body mass index, BMI））无显著差异。入院病因方面，内科首诊占比分别为HLI组49%、非HLI组34%（p=0.07）；择期手术占比分别为9%与38%（p<0.001）；急诊手术占比分别为43%与28%（p=0.06）。HLI组与非HLI组患者的查尔森合并症指数（Charlson Comorbidity Index, CCI）及更新版CCI的中位数分别为2（1~3）、2（1~2）与1（0~2）、1（0~2）（p<0.01及p=0.08）。HLI组患者入院时的简化急性生理学评分II（Simplified Acute Physiology Score II, SAPS II）更高（55分 vs 36分，p<0.001），且更需要接受机械通气（66% vs 34%，p<0.001）、血管活性药物治疗（91% vs 40%，p<0.001）、肾脏替代治疗（20% vs 2%，p<0.001）与肠外营养（29% vs 7%，p<0.001）。HLI组的ICU病死率与住院病死率分别为66%（n=23）与83%（n=29），而非HLI组分别为17%（n=170）与28%（n=292），两组差异均具有统计学意义（均p<0.001）。回归分析显示，SAPS II评分[比值比（odds ratio, OR）1.05，95%置信区间（95% confidence interval, CI）1.02~1.07；p<0.001]与血管活性药物治疗[OR 9.21，95%CI 2.58~32.86；p<0.01]为新发HLI的独立相关因素。HLI的发生与病死率独立相关[风险比（hazard ratio, HR）2.23，95%CI 1.50~3.30；p<0.001]。

讨论与结论：HLI在≥90岁的重症患者中属于少见但并非罕见的病症。HLI的发生与高病死率相关，其主要病因为心源性或感染性休克。HLI可作为≥90岁重症患者的早期预后标志物。