HBV相关慢加急性肝衰竭TBil水平的合理界值分析

Determination of a reasonable threshold of total bilirubin for the diagnosis of hepatitis B virus-associated acute-on-chronic liver failure

目的探讨HBV相关慢加急性肝衰竭(HBV-ACLF)患者的合理胆红素诊断阈值,以期更为精准地早期诊断。方法回顾性分析解放军总医院第五医学中心2008年9月—2018年9月收治的1232例HBV-ACLF患者,根据基线血清TBil水平分为A组(TBil<205.2μmol/L)和B组(TBil≥205.2μmol/L),比较2组患者临床特征及28 d、90 d、1年及3年生存情况。计量资料两组间比较采用t检验或Mann-Whitney U秩和检验。计数资料组间比较采用χ^(2)检验。使用Kaplan-Meier法分析2组患者的生存率,并应用log-rank检验进行比较。结果2组间年龄(t=3.188,P=0.001)、男性(χ^(2)=33.833,P<0.001)、肝衰竭分型(χ^(2)=39.987,P<0.001)、WBC(Z=6.586,P<0.001)、HGB(Z=4.272,P<0.001)、PLT(Z=3.680,P<0.001)、Cr(Z=4.505,P<0.001)、TC(Z=8.644,P<0.001)、Na(Z=2.335,P=0.020)、白蛋白(Z=2.592,P=0.010)、HBV DNA(Z=3.703,P<0.001)、MELD评分(Z=11.828,P<0.001)、MELD-Na评分(Z=8.410,P<0.001)比较差异均有统计学意义。基线时2组间腹水、GIB发生率比较差异均有统计学意义(χ^(2)值分别为12.036、4.342,P值均<0.05)。28 d内最常见的新发并发症是感染,其次为HE,2组间感染发生率比较差异有统计学意义(χ^(2)=5.294,P<0.05)。A组和B组HBV-ACLF患者28 d无移植病死率分别为21.2%和29.5%[HR=1.473(95%CI:1.151~1.886),P=0.005],均符合ACLF患者短期高死亡率的临床特征(>15%)。尽管两组患者长期病死率存在差异,但生存曲线显示,两组患者无移植病死率在90 d后均无显著上升。结论在INR≥1.5的前提下,不建议将HBV-ACLF诊断标准中TBil水平的界值提高至205.2μmol/L,确保更多ACLF患者早期诊断,从而获得更多救治机会,尽可能实现早期诊断增加救治机会。

Objective To investigate a reasonable threshold of total bilirubin for the diagnosis of hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF),and to realize accurate early diagnosis.Methods A retrospective analysis was performed for the clinical data of 1232 patients with HBV-ACLF who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from September 2008 to September 2018,and according to the baseline serum level of total bilirubin(TBil),the patients were divided into group A(TBil<205.2μmol/L)and group B(TBil≥205.2μmol/L).the two groups were compared in terms of clinical features and 28-day,90-day,1-year,and 3-year survival.The t-test or the Mann-Whitney U rank sum test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.The Kaplan-Meier method was used to analyze survival rate,and the log-rank test was used for comparison.Results There were significant differences between the two groups in age(t=3.188,P=0.001)male sex(χ^(2)=33.833,P<0.001),liver failure classification(χ^(2)=39.987,P<0.001),white blood cell count(Z=6.586,P<0.001),hemoglobin(Z=4.272,P<0.001),platelet count(Z=3.680,P<0.001),creatinine(Z=4.505,P<0.001),total cholesterol(Z=8.644,P<0.001),Na(Z=2.335,P=0.020),albumin(Z=2.592,P=0.010),HBV DNA(Z=3.703,P<0.001),Model for End-Stage Liver Disease score(Z=11.828,P<0.001),and MELD-Na score(Z=8.410,P<0.001).At baseline,there were significant differences in the incidence rates of ascites and gastrointestinal bleeding between the two groups(χ^(2)=12.036、4.342,P<0.05).Infection was the most common new-onset complication within 28 days,followed by hepatic encephalopathy,and there was a significant difference in the incidence rate of infection between the two groups(χ^(2)=5.294,P<0.05).The 28-day transplant-free mortality rate was 21.2%in group A and 29.5%in group B(HR=1.473[95%CI:1.151~1.886],P=0.005),which was consistent with the clinical feature of a high short-term mortality rate(>15%)in patients with acute-on-chronic liver failure(ACLF).Although there was a difference in long-term mortality rate between the two groups,there was no significant increase in transplant-free mortality rate after 90 days in either group.Conclusion Under the premise of international normalized ratio≥1.5,it is not recommended to increase the threshold of TBil to 205.2μmol/L in the diagnostic criteria for HBV-ACLF,so as to ensure the early diagnosis of more ACLF patients and bring more opportunities for treatment and cure.