慢加急性肝衰竭分型新视点:基于临床转归的动态分型新标准

目的分析慢加急性肝衰竭(ACLF)的疾病进程特点,探索新型判断慢加急性肝衰竭预后的分型标准,为制定更为精准化的治疗方案提供依据。方法纳入两所三甲医院确诊ACLF患者388例,收集患者人口学特征、临床检查信息、诊疗经过等信息,收集自诊断ACLF起第1、3、7、14、21、28 d和第12周或好转出院前、肝移植或病死前24 h的实验室检查数据,根据患者凝血酶原活动度(PTA)变化趋势,将其在4周内以及12周内的变化情况分为:升高至>40%,升高但仍≤40%,进行性下降或持续不升;而总胆红素(TBil)变化趋势分为:下降程度≥50%,下降程度<50%,进行性升高或者持续不降;筛选符合动态分型要求的患者,综合每个患者在第4、12周PTA、TBil变化趋势以及其预后情况,制定转归动态分型,采用χ2检验分析各分型ACLF患者临床特点。结果经过筛选,共262例患者入组,在病程第4周,有45%的患者PTA升高至>40%,40.8%的患者TBil下降50%,病程进展至12周时,累计有65.3%患者PTA升高至>40%,63.4%患者TBil下降50%;结合患者在第4、12周的预后情况,将患者病情演变过程分成5种类型:A型:快速进展型60例(22.9%);B型:快速恢复型82例(31.3%);C型:缓慢进展型48例(18.3%);D型:缓慢恢复型43例(16.4%);E型:缓慢持续型29例(11.1%)。快速进展型患者中合并上消化道出血、肝性脑病、急性肾损伤的比例分别为16.7%、33.3%、33.3%;而上述并发症在快速恢复型中仅占3.7%、7.3%、12.2%,χ2值分别为14.411、20.060、12.140,P值均<0.05,差异均有统计学意义。真菌感染率在病死或肝移植患者(即快速进展型与缓慢进展型患者)中分别为21.7%、10.4%,在快速恢复型、缓慢恢复型和缓慢持续型患者中分别为1.2%、14%、6.9%,快速进展型与快速恢复型之间差异有统计学意义,χ2=18.925,P<0.05。结论ACLF患者的病情发展过程可分为快速进展型、快速恢复型、缓慢进展型、缓慢恢复型、缓慢持续型,肝病基础、伴有真菌感染、消化道出血、肝性脑病、急性肾损伤均可影响ACLF病情发展。

A new perspective on acute-on-chronic liver failure based on clinical outcome of dynamic classification criteria

Objective To analyze the clinical characteristics among types of acute-on-chronic liver failure(ACLF)and explore the new classification criteria for judging the prognosis of acute-on-chronic liver failure,so as to provide a basis for the formulation of more precise therapeutic schedule.Methods 388 cases with ACLF diagnosed in two tertiary level hospitals were included.Patients demographic characteristics,clinical examination information,diagnostic and treatment process information were collected.Laboratory examination data of day 1,3,7,14,21,28 and of week 12 or prior to discharge after improvement and at 24 h prior to liver transplantation or death from the diagnosis of ACLF were collected.According to the change trend of the patient's prothrombin activity(PTA),the changes within 4 weeks and 12 weeks were divided into:increased to>40%,increase but still≤40%,progressively decreasing or not continuously rising.Moreover,the change trend of total bilirubin(TBil)was divided into:decreasing degree≥50%,decreasing degree<50%,progressively increasing or not decreasing.Patients meeting the requirements of dynamic classification were screened.PTA and TBil variation tendency of each patient at week 4 and 12 was synthesized,and prognostic condition for dynamic classification was formulated.The clinical characteristics of ACLF patients were analyzed byχ2 test.Results A total of 262 screened cases were enrolled.At the 4th week of the course of disease,45%of the patients'PTA had increased to>40%,and 40.8%of the patients'TBIL had decreased by 50%.When the course of disease was progressed to 12 weeks,65.3%of the patients'PTA had increased to>40%,and 63.4%of the patients'TBIL had decreased by 50%.Combined with the prognosis of the patients at the 4th and 12th week,the patients'disease evolution process was divided into five types:Type A:60 cases(22.9%)of rapid progression;Type B:82 cases(31.3%)of rapid recovery;Type C:48 cases(18.3%)of slow progression;Type D:43 cases(16.4%)of slow recovering;Type E:29 cases(11.1%)of slow persistence.The proportions of patients with rapid progression combined with upper gastrointestinal hemorrhage,hepatic encephalopathy,and acute renal injury were 16.7%,33.3%,and 33.3%,respectively;while the above-mentioned complications accounted for 3.7%,7.3%,and 12.2%only in the rapid recovery type,χ2=14.411,20.060,12.140,P<0.05,and the differences were statistically significant.Fungal infection rates were 21.7%,and 10.4%in patients who died of disease or liver transplantation(i.e.,patients with rapid progression and slow-progressing types),respectively,and 1.2%,14%,and 6.9%in patients with rapid progression type,slow-recovering type,and slow persistence type,respectively,and the difference between the rapid progression type and the rapid recovery type was significant,χ2=18.925,and the difference was statistically significant(P<0.05).Conclusion The course of disease progression in ACLF patients can be divided into rapid progression type,rapid recovery type,slow progression type,slow recovering type,and slow persistence type.The basis of liver disease,accompanied with fungal infection,gastrointestinal hemorrhage,hepatic encephalopathy and acute renal injury can affect the development of ACLF.