Qiao Liang, Tan Wenting, Wang Xiaobo, Zheng Xin, Huang Yan, Li Beiling, Meng Zhongji, Gao Yanhang, Qian Zhiping, Liu Feng, Lu Xiaobo, Shang Jia, Liu Junping, Yan Huadong, Gu Wenyi, Zhang Yan, Xiang Xiaomei, Hou Yixin, Zhang Qun, Xiong Yan, Zou Congcong, Chen Jun, Huang Zebing, Jiang Xiuhua, Luo Sen, Chen Yuanyuan, Gao Na, Liu Chunyan, Yuan Wei, Mei Xue, Li Jing, Li Tao, Zheng Rongjiong, Zhou Xinyi, Chen Jinjun, Deng Guohong, Zhang Weituo, Li Hai
Department of Gastroenterology, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China.
Key Laboratory of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Chinese Ministry of Health, Shanghai Jiao Tong University, Shanghai, China.
Front Med (Lausanne). 2021 Jun 23;8:704452. doi: 10.3389/fmed.2021.704452. eCollection 2021.
Total bilirubin (TB) is a major prognosis predictor representing liver failure in patients with acute on chronic liver failure (ACLF). However, the cutoff value of TB for liver failure and whether the same cutoff could be applied in both cirrhotic and non-cirrhotic patients remain controversial. There is a need to obtain the quantitative correlation between TB and short-term mortality evidence-based methods, which is critical in establishing solid ACLF diagnostic criteria. Patients hospitalized with cirrhosis or advanced fibrosis (FIB-4 > 1.45) were studied. TB and other variables were measured at baseline. The primary outcome was 90-day transplantation-free mortality. Multi-variable Cox proportional hazard model was used to present the independent risk of mortality due to TB. Generalized additive model and second derivate (acceleration) were used to plot the "TB-mortality correlation curves." The mathematical (maximum acceleration) and clinical (adjusted 28-day transplantation-free mortality rate reaching 15%) TB cutoffs for liver failure were both calculated. Among the 3,532 included patients, the number of patients with cirrhosis and advanced fibrosis were 2,592 and 940, respectively, of which cumulative 90-day mortality were 16.6% (430/2592) and 7.4% (70/940), respectively. Any increase of TB was found the independent risk factor of mortality in cirrhotic patients, while only TB >12 mg/dL independently increased the risk of mortality in patients with advanced fibrosis. In cirrhotic patients, the mathematical TB cutoff for liver failure is 14.2 mg/dL, with 23.3% (605/2592) patients exceeding it, corresponding to 13.3 and 25.0% adjusted 28- and 90-day mortality rate, respectively. The clinical TB cutoff for is 18.1 mg/dL, with 18.2% (471/2592) patients exceeding it. In patients with advanced fibrosis, the mathematical TB cutoff is 12.1 mg/dL, 33.1% (311/940) patients exceeding it, corresponding to 2.9 and 8.0% adjusted 28- and 90-day mortality rate, respectively; the clinical TB cutoff was 36.0 mg/dL, 1.3% (12/940) patients above it. This study clearly demonstrated the significantly different impact of TB on 90-day mortality in patients with cirrhosis and advanced fibrosis, proving that liver failure can be determined by TB alone in cirrhosis but not in advanced fibrosis. The proposed TB cutoffs for liver failure provides solid support for the establishment of ACLF diagnostic criteria.
总胆红素（TB）是急性慢性肝衰竭（ACLF）患者肝衰竭的主要预后预测指标。然而，TB用于肝衰竭的临界值以及该临界值是否适用于肝硬化和非肝硬化患者仍存在争议。需要通过循证方法获得TB与短期死亡率之间的定量相关性，这对于建立可靠的ACLF诊断标准至关重要。对因肝硬化或晚期纤维化（FIB-4>1.45）住院的患者进行了研究。在基线时测量TB和其他变量。主要结局是90天无移植死亡率。采用多变量Cox比例风险模型来呈现TB导致死亡的独立风险。使用广义相加模型和二阶导数（加速度）绘制“TB-死亡率相关曲线”。计算了肝衰竭的数学（最大加速度）和临床（调整后的28天无移植死亡率达到15%）TB临界值。在纳入的3532例患者中，肝硬化和晚期纤维化患者分别为2592例和940例，其中90天累积死亡率分别为16.6%（430/2592）和7.4%（70/940）。发现TB的任何升高都是肝硬化患者死亡的独立危险因素，而仅TB>12mg/dL会独立增加晚期纤维化患者的死亡风险。在肝硬化患者中，肝衰竭的数学TB临界值为14.2mg/dL，超过该值的患者有23.3%（605/2592），对应的调整后28天和90天死亡率分别为13.3%和25.0%。临床TB临界值为18.1mg/dL，超过该值的患者有18.2%（471/2592）。在晚期纤维化患者中，数学TB临界值为12.1mg/dL，超过该值的患者有33.1%（311/940），对应的调整后28天和90天死亡率分别为2.9%和8.0%；临床TB临界值为36.0mg/dL，超过该值的患者有1.3%（12/940）。这项研究清楚地表明了TB对肝硬化和晚期纤维化患者90天死亡率的影响存在显著差异，证明在肝硬化中仅通过TB即可确定肝衰竭，而在晚期纤维化中则不行。所提出的肝衰竭TB临界值为ACLF诊断标准的建立提供了有力支持。
