Wang Ying, Dong Fuchen, Sun Shuning, Wang Xianbo, Zheng Xin, Huang Yan, Li Beiling, Gao Yanhang, Qian Zhiping, Liu Feng, Lu Xiaobo, Liu Junping, Ren Haotang, Zheng Yubao, Yan Huadong, Deng Guohong, Qiao Liang, Zhang Yan, Gu Wenyi, Xiang Xiaomei, Zhou Yi, Xu Baoyan, Hou Yixin, Zhang Qun, Xiong Yan, Zou Congcong, Chen Jun, Huang Zebing, Jiang Xiuhua, Qi Tingting, Luo Sen, Chen Yuanyuan, Gao Na, Liu Chunyan, Yuan Wei, Mei Xue, Li Jing, Li Tao, Zheng Rongjiong, Zhou Xinyi, Zhang Weituo, Li Hai, Meng Zhongji
Department of Infectious Disease, Hubei Clinical Research Center for Precise Diagnosis and Treatment of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
Chinese Chronic Liver Failure Consortium, China.
Front Med (Lausanne). 2021 Nov 18;8:762291. doi: 10.3389/fmed.2021.762291. eCollection 2021.
An increase in the international normalized ratio (INR) is associated with increased mortality in patients with cirrhosis and other chronic liver diseases, while little is known about the quantitative relationship. This study aimed to investigate the quantitative relationship between the INR and short-term prognosis among patients hospitalized with cirrhosis or advanced fibrosis and to evaluate the role of the INR as a risk factor for short-term liver transplant (LT)-free mortality in these patients. This study prospectively analyzed multicenter cohorts established by the Chinese Acute-on-Chronic Liver Failure (CATCH-LIFE) study. Cox regression was used to describe the relationship between the INR and independent risk factors for short-term LT-free mortality. Forest plots were used in the subgroup analysis. Generalized additive models (GAMs) and splines were used to illustrate the quantitative curve relationship between the INR and the outcome and inflection point on the curve. A total of 2,567 patients with cirrhosis and 924 patients with advanced fibrosis were included in the study. The 90-day LT-free mortality of patients with cirrhosis and advanced fibrosis was 16.7% (428/2,567) and 7.5% (69/924), respectively. In the multivariable Cox regression analysis, the increase in the INR was independently associated with the risk of 90-day LT-free mortality both in patients with cirrhosis (HR, 1.06; 95% CI, 1.04-1.07, < 0.001) and in patients with advanced fibrosis (HR, 1.09; 95% CI, 1.06-1.12, < 0.001). An INR of 1.6/1.7 was found to be the starting point of coagulation dysfunction with a rapid increase in mortality in patients with cirrhosis or in patients with advanced fibrosis, respectively. A 28-day LT-free mortality of 15% was associated with an INR value of 2.1 in both cirrhosis and advanced fibrosis patients. This study was the first to quantitatively describe the relationship between the INR and short-term LT-free mortality in patients with cirrhosis or advanced fibrosis. The starting points of INR indicating the rapid increase in mortality and the unified cutoff value of coagulation failure in cirrhosis and advanced fibrosis, will help clinicians accurately recognize early disease deterioration.
国际标准化比值（INR）升高与肝硬化及其他慢性肝病患者的死亡率增加相关，但关于两者的定量关系却知之甚少。本研究旨在探讨肝硬化或晚期肝纤维化住院患者INR与短期预后之间的定量关系，并评估INR作为这些患者短期无肝移植（LT）死亡风险因素的作用。本研究对中国慢加急性肝衰竭（CATCH-LIFE）研究建立的多中心队列进行了前瞻性分析。采用Cox回归描述INR与短期无LT死亡独立危险因素之间的关系。亚组分析采用森林图。使用广义相加模型（GAMs）和样条函数来说明INR与结局之间的定量曲线关系以及曲线上的拐点。本研究共纳入2567例肝硬化患者和924例晚期肝纤维化患者。肝硬化和晚期肝纤维化患者的90天无LT死亡率分别为16.7%（428/2567）和7.5%（69/924）。在多变量Cox回归分析中，INR升高与肝硬化患者（HR，1.06；95%CI，1.04-1.07，P<0.001）和晚期肝纤维化患者（HR，1.09；95%CI，1.06-1.12，P<0.001）90天无LT死亡风险独立相关。结果发现，INR为1.6/1.7分别是肝硬化患者或晚期肝纤维化患者凝血功能障碍的起始点，此时死亡率迅速上升。肝硬化和晚期肝纤维化患者28天无LT死亡率为15%时，INR值均为2.1。本研究首次定量描述了肝硬化或晚期肝纤维化患者INR与短期无LT死亡之间的关系。INR提示死亡率迅速上升的起始点以及肝硬化和晚期肝纤维化凝血功能衰竭的统一临界值，将有助于临床医生准确识别疾病早期恶化情况。
