Division of Gastroenterology and Hepatology, Mayo Clinic in Arizona, Phoenix, Arizona, USA.
Division of Gastroenterology (Liver Unit), Division of Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada.
Clin Transl Gastroenterol. 2023 Apr 1;14(4):e00565. doi: 10.14309/ctg.0000000000000565.
There has been a growing interest in identifying prognostic biomarkers that alone or with available prognostic models (King's College Criteria, KCC; MELD and ALFSG Prognostic Index) would improve prognosis in acute liver failure (ALF) patients being assessed for liver transplantation. The Acute Liver Failure Study Group (ALFSG) has evaluated 15 potential prognostic biomarkers: serum AFP; apoptosis-associated proteins; serum actin-free Gc-globulin; serum glycodeoxycholic acid; sRAGE/RAGE ligands; plasma osteopontin; circulating MBL, M-, L-, H-ficolin and CL-1; plasma galectin-9; serum FABP1; serum Lct2; miRNAs; factor V; thrombocytopenia, and sCD163. The ALFSG also has reported on 4 susceptibility biomarkers: keratins 8 and 18 (K8/K18) gene variants; polymorphisms of genes encoding putative APAP-metabolizing enzymes ( UGT1A1 , UGT 1A0 , UGT 2B15 , SULT1A1 , CYP2E1 , and CYP3A5 ) as well as CD44 and BHMT1 ; single nucleotide polymorphisms (SNPs) of genes associated with human behavior, rs2282018 in the arginine vasopressin ( AVP ) gene and rs11174811 in the AVP receptor 1A gene. Finally, rs2277680 of the CSCL16 gene in HBV-ALF patients. In conclusion, we have reviewed the prognostic and susceptibility biomarkers studied by the ALFSG. We suggest that a better approach to predicting the clinical outcome of an ALF patient will require a combination of biomarkers of pathogenic processes such as cell death, hepatic regeneration, and degree of inflammation that could be incorporated into prognostic models such as KCC, MELD or ALFSG PI.
人们越来越关注寻找预后生物标志物，这些标志物单独或与现有的预后模型（国王学院标准、KCC；MELD 和 ALFSG 预后指数）一起，可以改善接受肝移植评估的急性肝衰竭（ALF）患者的预后。急性肝衰竭研究组（ALFSG）已经评估了 15 种潜在的预后生物标志物：血清 AFP；凋亡相关蛋白；血清无肌动蛋白 Gc-球蛋白；血清甘氨脱氧胆酸；sRAGE/RAGE 配体；血浆骨桥蛋白；循环 MBL、M、L、H-ficolin 和 CL-1；血浆半乳糖凝集素-9；血清 FABP1；血清 Lct2；miRNAs；因子 V；血小板减少症和 sCD163。ALFSG 还报告了 4 种易感性生物标志物：角蛋白 8 和 18（K8/K18）基因突变；编码潜在 APAP 代谢酶的基因多态性（UGT1A1、UGT1A0、UGT2B15、SULT1A1、CYP2E1 和 CYP3A5）以及 CD44 和 BHMT1；与人类行为相关的基因单核苷酸多态性（SNP），精氨酸加压素（AVP）基因中的 rs2282018 和 AVP 受体 1A 基因中的 rs11174811。最后，HBV-ALF 患者 CSCL16 基因中的 rs2277680。总之，我们回顾了 ALFSG 研究的预后和易感性生物标志物。我们认为，预测 ALF 患者临床结局的更好方法将需要结合细胞死亡、肝再生和炎症程度等致病过程的生物标志物，这些标志物可以纳入 KCC、MELD 或 ALFSG PI 等预后模型中。
