Zhang Lingjian, Zhao Yalei, Xie Zhongyang, Xiao Lanlan, Hu Qingqing, Li Qian, Tang Shima, Wang Jie, Li Lanjuan
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
J Clin Transl Hepatol. 2022 Aug 28;10(4):651-659. doi: 10.14218/JCTH.2021.00347. Epub 2022 Jan 10.
1,5-Anhydroglucitol (1,5AG) activity has been reported in chronic liver disease. Hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF) patients have a high mortality. We aimed to discover the relationship between serum 1,5AG and the prognosis of HBV-ACLF.
Serum 1,5AG levels were determined in 333 patients with HBV-ACLF, 300 without diabetes were allocated to derivation (n=206) and validation cohorts (n=94), and 33 were recruited to evaluate 1,5AG in those with diabetes. Forty patients with chronic hepatitis B, 40 with liver cirrhosis, and 40 healthy people were controls in the validation cohort.
In the derivation and validation cohorts, serum 1,5AG levels were significantly lower in nonsurvivors than in survivors. The AUC of 1,5AG for 28-day mortality was 0.811. In patients with diabetes, serum 1,5AG levels were also significantly lower in nonsurvivors than in survivors. In multivariate Cox regression analysis, serum 1,5AG levels were independently associated with 28-day mortality. A novel predictive model (ACTIG) based on 1,5AG, age, TB, cholesterol, and INR was derived to predict mortality. In ACTIG, the AUC for 28-day mortality was 0.914, which was superior to some prognostic score models. ACTIG was also comparable to those prognostic score models in predicting 6-month mortality. In mice with D-galactosamine/lipopolysaccharide-induced liver failure, 1,5AG levels were significantly reduced in serum and significantly increased in urine and liver tissue.
Serum 1,5AG levels are a promising predictor of short-term mortality in HBV-ACLF patients. The 1,5AG distribution changed in mice with D-galactosamine/ lipopolysaccharide-induced liver failure.
慢性肝病患者中已报道有1,5-脱水葡萄糖醇（1,5AG）活性。乙型肝炎病毒（HBV）相关慢加急性肝衰竭（HBV-ACLF）患者死亡率很高。我们旨在探究血清1,5AG与HBV-ACLF患者预后之间的关系。
测定了333例HBV-ACLF患者的血清1,5AG水平，将300例无糖尿病患者分为推导队列（n = 206）和验证队列（n = 94），并招募了33例患者评估糖尿病患者的1,5AG水平。验证队列中，40例慢性乙型肝炎患者、40例肝硬化患者和40例健康人作为对照。
在推导队列和验证队列中，非存活者的血清1,5AG水平显著低于存活者。1,5AG预测28天死亡率的AUC为0.811。糖尿病患者中，非存活者的血清1,5AG水平也显著低于存活者。在多因素Cox回归分析中，血清1,5AG水平与28天死亡率独立相关。基于1,5AG、年龄、总胆红素、胆固醇和国际标准化比值（INR）构建了一种新型预测模型（ACTIG）来预测死亡率。在ACTIG模型中，预测28天死亡率的AUC为0.914，优于一些预后评分模型。ACTIG在预测6个月死亡率方面也与那些预后评分模型相当。在D-半乳糖胺/脂多糖诱导的肝衰竭小鼠中，血清1,5AG水平显著降低，尿液和肝组织中1,5AG水平显著升高。
血清1,5AG水平是HBV-ACLF患者短期死亡率的一个有前景的预测指标。D-半乳糖胺/脂多糖诱导的肝衰竭小鼠中1,5AG分布发生了变化。
