Maiwall Rakhi, Pasupuleti Samba Siva Rao, Rastogi Archana, Sharma Fagun, Hidam Ashini Kumar, Thomas Sherin, Sarin Shiv Kumar
Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India.
Department of Statistics, Mizoram University (A Central University), Pachhunga University College Campus, Aizawl, India.
Hepatol Int. 2025 Feb;19(1):222-233. doi: 10.1007/s12072-024-10749-4. Epub 2024 Nov 28.
Acute-on-chronic liver failure (ACLF) patients with hepatorenal syndrome (HRS-AKI) have limited response to vasoconstrictors and worse outcomes, requiring biomarkers for early detection.
In a prospective cohort of ACLF patients (n = 240), urine NGAL was performed in patients with the clinical diagnosis of HRS-AKI, while in a subset of patients (n = 30), a complete panel of 17 urinary biomarkers was assessed for identifying terlipressin non-response (T-NR).
ACLF patients with HRS-AKI, aged 45.84 ± 10.6 years, 91.2% males, 74.2% with alcohol etiology, mean urine NGAL of 1541.66 ± 1684.69 ng/ml, AARC score 10.19 ± 1.86, 155 (64.5%) had T-NR at day 4. T-NR was maximal for AARC grade 3 and was associated with a higher need of dialysis (50.3% vs 5.9%; OR 16.21, 6.23-42.19) and 28-day mortality (49.0% vs. 17.9%; HR 3.42, 1.96-5.95). AARC grade 3 (OR 38.21, 2.93-497.74), (HR 5.10, 1.19-21.84) and urine NGAL (OR 11.53, 5.66-23.49; AUROC 0.97, NGAL > 900 ng/ml) (HR 1.23, 1.02-1.49) were independent predictors of T-NR and 28-day mortality, respectively. It was interesting to observe a significant elevation in renal injury and a decrease in the repair markers in T-NR (p < 0.05).
Almost 60% of patients with ACLF and HRS-AKI experience non-response to terlipressin which predicts higher mortality and need for dialysis. High NGAL above 900 ng/ml predicts T-NR with 100% specificity for T-NR. ACLF patients with HRS, with AARC grade 3 and high NGAL have a high likelihood of T-NR and should be considered for alternative therapeutic modalities.
伴有肝肾综合征（HRS-AKI）的慢加急性肝衰竭（ACLF）患者对血管收缩剂反应有限且预后较差，需要生物标志物进行早期检测。
在一个ACLF患者的前瞻性队列（n = 240）中，对临床诊断为HRS-AKI的患者检测尿中性粒细胞明胶酶相关脂质运载蛋白（NGAL），而在一部分患者（n = 30）中，评估一组完整的17种尿生物标志物以识别特利加压素无反应（T-NR）情况。
患有HRS-AKI的ACLF患者，年龄45.84±10.6岁，男性占91.2%，74.2%有酒精性病因，平均尿NGAL为1541.66±1684.69 ng/ml，急性肾损伤风险分级（AARC）评分为10.19±1.86，155例（64.5%）在第4天出现T-NR。AARC 3级患者T-NR情况最为严重，且与更高的透析需求（50.3%对5.9%；比值比16.21，6.23 - 42.19）和28天死亡率（49.0%对17.9%；风险比3.42，1.96 - 5.95）相关。AARC 3级（比值比38.21，2.93 - 497.74），（风险比5.10，1.19 - 21.84）和尿NGAL（比值比11.53，5.66 - 23.49；曲线下面积0.97，NGAL＞900 ng/ml）（风险比1.23，1.02 - 1.49）分别是T-NR和28天死亡率的独立预测因素。有趣的是，观察到T-NR患者肾损伤显著升高且修复标志物降低（p＜0.05）。
几乎60%的ACLF和HRS-AKI患者对特利加压素无反应，这预示着更高的死亡率和透析需求。NGAL高于900 ng/ml对T-NR的预测特异性为100%。AARC 3级且NGAL高的ACLF合并HRS患者T-NR可能性高，应考虑采用替代治疗方式。
