13C-美沙西丁呼气试验在评价慢加急性肝功能衰竭患者肝储备功能和预后中的应用

The application of 13C-methacetin breath test in the assessment of reserved liver function and prognosis of patients with acute on chronic liver failure

目的 观察慢加急性肝功能衰竭患者13C-美沙西丁呼气试验（13C-MBT）检测的特点,探讨13C-MBT对慢加急性肝功能衰竭患者肝储备功能评价和预后判断的价值.方法 对87例慢加急性肝功能衰竭（分为早期、中期和晚期3个亚组）、36例慢性肝炎（包括轻度和中度）、56例肝硬化患者（代偿性肝硬化Child-Pugh A级）进行研究.行13C-MBT、肝功能、肾功能、凝血功能检测,计算终末期肝病模型（MELD）值,记录13C-MBT的3个主要参数——前40 min代谢速率峰值与正常值的比值（MVmax40）、前40 min 13CO2累积呼出丰度与正常值的比值（CUM40）、前120 min13CO2累积呼出丰度与正常值的比值（CUM120）,计算量化值,绘制丰度（DOB）曲线、代谢速率（MV）曲线.慢加急性肝功能衰竭患者随访3个月,分为存活组（43例）和病死组（44例）,对13C-MBT量化值、TBil、PTA、国际标准化比率（INR）、MELD和Cr行受试者工作特征曲线（ROC曲线）分析.结果 慢性肝炎组、肝硬化组和慢加急性肝功能衰竭组13C-MBT的MVmax40（0.70±0.14、0.34±0.09、0.14±0.07,F=38.08,P＜0.01）、CUM40 （0.75±0.17、0.34±0.09、0.11±0.06,F=18.23,P＜0.01）、CUM120（0.74±0.18、0.46±0.13、0.21±0.11,F=21.56,P＜0.01）和量化值（0.73±0.15、0.34±0.13、0.21±0.11,F=17.82,P＜0.01）的差异均有统计学意义,慢加急性肝功能衰竭早期、中期、晚期各亚组间MVmax40、CUM40、CUM120和量化值差异亦有统计学意义（F值分别为6.34、5.53、11.12和10.97,均P＜0.05）.慢加急性肝功能衰竭组13C-MBT量化值、TBil、PTA、INR、MELD、Cr的ROC曲线下面积分别为0.71、0.67、0.80、0.81、0.88和0.87,当13C-MBT量化值为0.14时,对预后判断的敏感度为63.6％,特异度为69.8％.13C-MBT量化值以0.14为界进行3个月预后分析,13C-MBT量化值≥0.14,病死率为22.45％ （11/49）;13C-MBT量化值＜0.14,病死率为86.84％（33/38,x2=4.89,P＜0.05）.结论 MVmax40 、CUM40、CUM120和量化值随着肝脏储备功能的下降而减低,可用于慢加急性肝功能衰竭患者肝储备功能的评价.MELD诊断价值最高,但13C-MBT相对独立,是评价慢加急性肝功能衰竭患者肝脏储备功能和预后的有益补充,当其量化值＜0.14时预后较差.

Objective To investigate the clinical value of 13C-methacetin breath test （13C MBT） in the assessment of reserved liver function and prognosis of patients with acute on chronic liver failure by observing the characteristic of 13C-MBT.Methods Eighty-seven patients with acute on chronic liver failure （divided into early,middle and late stage subgroups）,36 patients with chronic hepatitis （mild or moderate type） and 56 patients with cirrhosis （compensative cirrhosis with Child-Pugh score of A） serving as controls were included in this study.All subjects received 13C-MBT,routine liver function test,renal function test and coagulation test after an overnight fast.Meanwhile model for end-stage liver disease （MELD） score was calculated.The three major parameters of 13C-MBT,i.e.maximum excretion rate before 40 min （MVmax40）,13CO2 cumulative excretion of 40 min （CUM40） and that of 120 min （CUM120） were recorded,and quantification value was calculated.Two metabolism curves （delta over baseline and metabolisation velosity curve） were drawn.Patients with acute on chronic liver failure were divided into survival group （43 patients） and death group （44 patients） by 3 months follow-up.Quantified value of 13C-MBT,total bilirubin （TBil）,prothrombin activity （PTA）,international normalized ratio （INR） and MELD were performed by the receiver-operator-characteristic curve analysis （ROC curve analysis）.Results The three parameters of 13C-MBT and the quantification value were all significantly statistically different among the three groups.In patients with acute on chronic liver failure,chronic hepatitis,and compensated cirrhosis,the MVmax40 were 0.70 ±0.14,0.34 ± 0.09 and 0.14 ±0.07,respectively （F=38.08,P〈0.01）,CUM40 were 0.75 ±0.17,0.34 ± 0.09 and 0.11±0.06,respectively （F=18.23,P〈0.01）,CUM120 were 0.74±0.18,0.46±0.13 and 0.21 ± 0.11,respectively （F=21.56,P〈0.01）,and the quantification values were 0.73 ± 0.15,0.34±0.13 and 0.21 ± 0.11,respectively （F =17.82,P〈 0.01）.For patients in subgroups with early,middle,and late stages of acute on chronic liver failure,the MVmax40,CUM40,CUM120,and the quantification values,the differences were significant （F=6.34,5.53,11.12,and 10.97,all P〈0.05）.The area under curve （AUC） of quantification value of 13C-MBT,TBil,PTA,INR,MELD and Cr were 0.71,0.67,0.80,0.81,0.88,and 0.87,respectively.When the quantification value of 13C-MBT was equal to 0.14,the sensitivity was 63.6% and specificity was 69.8% in the assessment of prognosis.Prognostic analysis of 3 month survival with 13C-MBT quantification cut off value of 0.14 showed that the mortality rate was 22.45% （11/49） when 13C-MBT quantification values were≥0.14,and 86.84 % （33/38） when 13C-MBT quantification values were 〈0.14 （x2 =4.89,P〈 0.05）.Conclusions The values of the three parameters and the quantification value of 13C-MBT decrease with the severity of the liver disease and 13C-MBT may be used to evaluate the reserved hepatic function in patients with acute on chronic liver failure.MELD is the best diagnostic method,while 13C-MBT is a better supplementary method to assess the reserved hepatic function and prognosis of patients with acute on chronic liver failure independently.When the quantification value of 13C-MBT is less than 0.14,the prognosis is poor.