乙型肝炎肝硬化急性恶化患者慢加急性肝衰竭的发生情况及预后分析

Development and prognosis of acute-on-chronic liver failure in patients with acute deterioration of hepatitis B virus-related liver cirrhosis

目的研究乙型肝炎肝硬化急性恶化(AD)患者28 d发生慢加急性肝衰竭(ACLF)的情况以及90 d预后分析。方法选取2014年10月-2016年10月解放军总医院第五医学中心收治的670例乙型肝炎肝硬化AD患者,根据TBil、PTA分为A组(134例,51.3μmol/L<TBil<171.1μmol/L且PTA<40%)、B组(393例,51.3μmol/L<TBil<171.1μmol/L且40%≤PTA<60%)、C组(143例,TBil>171.1μmol/L且40%<PTA<60%),研究患者的临床特征、28 d ACLF发生情况及其影响因素、90 d生存情况及其影响因素。正态分布计量资料多组间比较采用方差分析,进一步两两比较采用LSD-t检验。非正态分布计量资料多组间比较采用Kruskal-Wallis H检验。多组间计数资料比较采用χ^2检验或Fisher精确法。组间累积发生率计算采用Kaplan-Meier分析,组间比较采用log-rank检验。分别采用Cox回归、logistic回归分析ACLF发生以及90 d生存的影响因素。结果A、B、C三组间MELD评分以及Child-pugh评分差异显著(20.2±4.6 vs 14.7±3.6 vs 22.7±5.6,F=211.118,P<0.001;10.6±0.8 vs 9.3±1.2 vs 10.4±1.2,F=66.427,P<0.001),B组均低于A组和C组(P值均<0.05)。69例(10.3%)患者在28 d内发生ACLF,A组19例(14.2%)、B组17例(4.3%)、C组33例(23.1%)。B组ACLF发生率低于A组(χ^2=15.937,P<0.001)和C组(χ^2=48.502,P<0.001)。各组发生ACLF的独立性影响因素,A组为AST(RR=1.033,P=0.030)、细菌感染(BIs)(RR=14.326,P=0.001)、血钠(Na)(RR=0.888,P=0.019)、AFP(RR=1.003,P<0.001),B组为男性(RR=0.201,P=0.035)、ALT(RR=0.996,P=0.006)、AST(RR=1.008,P<0.001)、GGT(RR=1.004,P=0.018)、PTA(RR=0.642,P<0.001)、TBil(RR=1.039,P=0.002)、BIs(RR=49.656,P<0.001)、HBV DNA(RR=2.206,P<0.001),C组为急性静脉曲张破裂出血(AVB)(RR=3.172,P=0.025)、BIs(RR=2.946,P=0.007)。79例(11.8%)患者在90 d内死亡,A组29例(21.6%),B组15例(3.8%),C组35例(24.5%),B组均低于A组(χ^2=41.492,P<0.001)和C组(χ^2=52.905,P<0.001)。三组发生ACLF患者90 d病死率均高于各自未发生ACLF患者(A组:χ^2=4.151,P=0.042;B组:P=0.022;C组:χ^2=16.968,P<0.001)。各组90 d生存的独立性影响因素,A组为肌酐(OR=1.075,P=0.007)、Na(OR=0.450,P<0.001);B组为AVB(OR=1378.999,P=0.026)、Na(OR=0.392,P=0.018);C组为AVB(OR=31.699,P=0.038)、Na(OR=0.841,P=0.023)、发生ACLF(OR=14.258,P=0.017)。结论乙型肝炎肝硬化AD患者可分为三型,高黄疸型(C组)、低凝血型(A组)更容易出现ACLF且预后更差。BIs是三类患者发生ACLF共同的影响因素。血Na水平是三类患者90 d预后共同的影响因素。

Objective To investigate the 28-day incidence rate of acute-on-chronic liver failure(ACLF)and the 90-day prognosis of patients with acute deterioration(AD)of hepatitis B virus(HBV)-related liver cirrhosis(LC).Methods A total of 670 patients with AD of HBV-related LC who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from October 2014 to October 2016 were enrolled,and according to total bilirubin(TBil)and prothrombin time activity(PTA),they were divided into group A with 134 patients(51.3μmol/L<TBil<171.1μmol/L and PTA<40%),group B with 393 patients(51.3μmol/L<TBil<171.1μmol/L and 40%≤PTA<60%),and group C with 143 patients(TBil>171.1μmol/L and 40%<PTA<60%).The patients were analyzed in terms of clinical features,28-day incidence rate of ACLF and its influencing factors,and 90-day survival and its influencing factors.An analysis of variance was used for comparison of normally distributed continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups;the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups.The chi-square test or the Fisher’s exact test was used for comparison of categorical data between multiple groups.The Kaplan-Meier method was used to calculate cumulative incidence rate,and the log-rank test was used for comparison between groups.Cox regression analysis and logistic regression analysis were used to investigate the influencing factors for the onset of ACLF and 90-day survival.Results There were significant differences between groups A,B,and C in Model for End-Stage Liver Disease score(20.2±4.6 vs 14.7±3.6 vs 22.7±5.6,F=211.118,P<0.001)and Child-Pugh score(10.6±0.8 vs 9.3±1.2 vs 10.4±1.2,F=66.427,P<0.001),and group B had significantly lower scores than groups A and C(all P<0.05).Among the 670 patients,69(10.3%)developed ACLF within 28 days,with 19 patients(14.2%)in group A,17 patients(4.3%)in group B,and 33 patients(23.1%)in group C.Group B had a significantly lower incidence rate of ACLF than group A(χ^2=15.937,P<0.001)and group C(χ^2=48.502,P<0.001).In group A,aspartate aminotransferase(AST)(risk ratio[RR]=1.033,P=0.030),bacterial infections(BIs)(RR=14.326,P=0.001),blood sodium(Na)(RR=0.888,P=0.019),and alpha-fetoprotein(AFP)(RR=1.003,P<0.001)were independent influencing factors for ACLF;in group B,male sex(RR=0.201,P=0.035),alanine aminotransferase(RR=0.996,P=0.006),AST(RR=1.008,P<0.001),gamma-glutamyl transpeptidase(RR=1.004,P=0.018),PTA(RR=0.642,P<0.001),TBil(RR=1.039,P=0.002),BIs(RR=49.656,P<0.001),and HBV DNA(RR=2.206,P<0.001)were independent influencing factors for ACLF;in group C,acute variceal bleeding(AVB)(RR=3.172,P=0.025)and BIs(RR=2.946,P=0.007)were independent influencing factors for ACLF.Of all 670 patients,79(11.8%)died within 90 days,with 29 patients(21.6%)in group A,15 patients(3.8%)in group B,and 35 patients(24.5%)in group C,and group B had a significantly lower mortality rate than group A(χ^2=41.492,P<0.001)and group C(χ^2=52.905,P<0.001).In each group,the patients with ACLF had a significantly higher 90-day mortality rate than those without ACLF(group A:χ^2=4.151,P=0.042;group B:P=0.022;group C:χ^2=16.968,P<0.001).In group A,creatinine(odds ratio[OR]=1.075,P=0.007)and Na(OR=0.450,P<0.001)were independent influencing factors for 90-day survival;in group B,AVB(OR=1378.999,P=0.026)and Na(OR=0.392,P=0.018)were independent influencing factors for 90-day survival;in group C,AVB(OR=31.699,P=0.038),Na(OR=0.841,P=0.023),and development of ACLF(OR=14.258,P=0.017)were independent influencing factors for 90-day survival.Conclusion Patients with AD of HBV-related LC can be divided into three clinical types,and the patients with high jaundice type(group C)or low coagulation type(group A)tend to develop ACLF and have poorer prognosis.BIs are the common influencing factor for ACLF in these three types of patients,and blood Na level is the common influencing factor for 90-day prognosis.