Supplementary Material for: How to Define Acute Liver Failure Patients with Pre-Existing Liver Disease without Signs of Cirrhosis

<b><i>Background:</i></b> The definition of acute liver failure (ALF) usually implies no previous liver injury. Though, some patients admitted to liver transplantation centers with the diagnosis of ALF are obese or have diabetes. Elevated liver enzymes were not recorded previously, and no signs of cirrhosis or prior decompensation of the liver function were ever present. Still, these patients differ from the “typical” ALF-patient. <b><i>Goals:</i></b> In this study, we aimed to confirm acute-on-chronic-liver failure (AOCLF) in patients diagnosed with ALF and to identify possible differences between ALF and AOCLF. <b><i>Study:</i></b> Patients were retrospectively recruited from all patients admitted to the University Hospital Essen with diagnosis of ALF between 2008 and 2015. Data of 163 patients were evaluated, resulting in a reclassification of 32 patients as AOCLF (remaining ALF: 131). Demographic and clinical data as well as serum parameters, including cell death markers, were correlated with clinical outcome. <b><i>Results:</i></b> Patients with AOCLF were significantly older, had a higher body mass index (BMI), and were more often male. The cause for liver failure in these patients differed significantly from patients who had an actual ALF. Significant differences were also found for serum liver enzymes. Outcome of patients did not differ between AOCLF and ALF. Though, lower BMI and MELD and higher AST and GLDH were predictors for a beneficial outcome. <b><i>Conclusion:</i></b> AOCLF is still commonly misdiagnosed as ALF. While clinical outcome does not significantly differ between ALF and AOCLF, risk factors for adverse outcome may significantly differ between these entities.

<b><i>研究背景：</i></b> 急性肝衰竭（acute liver failure, ALF）的经典定义通常指既往无肝损伤病史。然而，部分因疑似ALF收治于肝移植中心的患者存在肥胖或糖尿病史，且既往未记录肝酶升高，亦无肝硬化或既往肝功能失代偿的征象，但此类患者与“典型”ALF患者存在差异。<b><i>研究目标：</i></b> 本研究旨在确认疑似ALF患者中是否存在慢加急性肝衰竭（acute-on-chronic-liver failure, AOCLF），并明确ALF与AOCLF之间可能存在的差异。<b><i>研究方案：</i></b> 本研究回顾性招募2008年至2015年间于埃森大学医院收治的确诊ALF患者，最终纳入163例患者的临床数据进行分析，其中32例被重新归类为AOCLF（剩余131例仍为ALF）。研究对患者的人口学特征、临床资料、包括细胞死亡标志物在内的血清学指标与临床结局的相关性进行了分析。<b><i>研究结果：</i></b> AOCLF患者年龄显著更高，体重指数（body mass index, BMI）更大，男性占比更高；此类患者的肝衰竭病因与真性ALF患者存在显著差异，血清肝酶水平亦存在显著差异。但AOCLF与ALF患者的临床结局无显著差异。此外，较低的BMI与终末期肝病模型（Model for End-Stage Liver Disease, MELD）评分、较高的天冬氨酸转氨酶（aspartate aminotransferase, AST）及谷氨酸脱氢酶（glutamate dehydrogenase, GLDH）水平是有利临床结局的预测因素。<b><i>研究结论：</i></b> 慢加急性肝衰竭（AOCLF）仍常被误诊为ALF。尽管二者的临床结局无显著差异，但两类患者发生不良结局的危险因素可能存在显著差异。