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摘要：
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摘要：目的 探讨血浆二胺氧化酶（diamine oxidase，DAO）浓度联合iMELD评分对乙型肝炎病毒
相关慢加急性肝衰竭（hepatitis B virus-related acute-on-chronic liver failure，HBV-ACLF）近期预
后的病毒预测价值。方法 选取2015年8月至2018年12月上海交通大学医学院附属新华医院崇明分
院收治的98例HBV-ACLF患者为HBV-ACLF组，选取54例同期健康体检者为对照组。根据随访1个
月后HBV-ACLF患者的预后分为生存组（66例）和病死组（32例）。检测各组血浆DAO、总胆固
醇（total cholesterol，TC）、甘油三酯（triglyceride，TG）、白蛋白（albumin，ALB）、总胆红
素（total bilirubin，TBil）、肌酐（serum creatinine，SCr）、血清钠、丙氨酸氨基转移酶（alanine
aminotransferase，ALT）、天门冬氨酸氨基转移酶（aspartate aminotransferase，AST）、凝血酶原时
间（prothrombin time，PT）及凝血酶原活动度（prothrombin activity，PTA）水平，计算MELD评分。
DAO、iMELD评分与各指标的相关性采用Pearson相关性分析，HBV-ACLF患者病死的危险因素采用
多因素Logistic回归分析，采用受试者工作特征（receiver operator characteristic，ROC）曲线分析DAO
和iMELD评分预测HBV-ACLF患者预后的价值。结果 HBV-ACLF组患者DAO水平[（105.87 ± 44.76）ng/ml
vs（8.65 ± 3.56）ng/ml]和iMELD评分[（44.63 ± 26.63）分vs （4.54 ± 2.23）分]显著高于对照组，差异
有统计学意义（t = 21.376、14.809，P ＜ 0.001）。病死组DAO水平[（116.63 ± 33.54）ng/ml vs（79.65 ±
18.52）ng/ml]和iMELD评分[（56.36 ± 16.63）分vs（28.65 ± 13.24）分]显著高于存活组，差异有统计学
意义（t = 23.654、18.654，P ＜ 0.001）。DAO、iMELD评分与AST、ALT、TBil、HBV DNA、TC、
TG呈正相关（r ＞ 0.4，P ＜ 0.05），与ALB、PTA、TC、TG呈负相关（r ＜ -0.4，P ＜ 0.05）。DAO ≥
105.87 ng/ml，iMELD ≥ 44.63分的HBV-ACLF患者，其腹水发生率（53.8% vs 15.0%，47.2% vs 7.2）、肝
肾综合征发生率（55.2% vs 15.0%，57.1% vs 21.4%）、肝硬化发生率（38.7% vs 10.0%，44.2% vs 5.6%）、肝
性脑病发生率（43.6% vs 10.0%，42.9% vs 21.4%）及病死率（40.0% vs 5.0%，42.9% vs 7.2%）分别显著高
于DAO ＜ 105.87 ng/ml，iMELD ＜ 44.63分的患者（P ＜ 0.05）。病死组患者ALT [（390.21 ± 10.23）U/L vs
（372.32 ± 10.54）U/L]、AST[（452.32 ± 11.25）U/L vs（441.32 ± 9.65）U/L]、HBV DNA [（9.63 ± 2.45）拷贝/ml vs
（5.96 ± 2.85）拷贝/ml]、TBil [（13654.36 ± 121.36）μmol/L vs（12065.36 ± 365.21）μmol/L]、PT [（36.96 ±
5.54）s vs（25.63 ± 8.65）s]、PTA [（37.69 ± 5.48）% vs（57.65 ± 5.24）%]、MELD评分[（30.36 ± 5.45）
分 vs（24.63 ± 5.63）分]、SCr [（149.32 ± 3.25）μmmol/L vs（142.32 ± 2.32）μmmol/L]、DAO [（116.63 ±
33.54）ng/ml vs（79.65 ± 18.52）ng/ml]及iMELD评分[（56.36 ± 16.63）分 vs（28.65 ± 13.24）分]显
著高于生存组，ALB [（18.32 ± 3.52）g/L vs（26.54 ± 3.45）g/L]显著低于生存组，差异有统计学意义
（P ＜ 0.05）。多因素Logistic回归分析表明，DAO ≥ 105.87 ng/ml、iMELD评分≥ 44.63分、HBV DNA＞
7.69拷贝/ml为HBV-ACLF患者病死的危险因素（OR = 2.36、2.48、3.16，P ＜ 0.05）。DAO + iMELD评分、
DAO及iMELD评分的ROC曲线下面积（area under curve，AUC）分别为0.834、0.814、0.798，差异有统
计学意义（z = 7.654，P ＜ 0.001）；DAO与iMELD评分的AUC差异无统计学意义（z = 1.654，P =
0.074），均显著小于DAO + iMELD评分（z = 11.654、10.905，P ＜ 0.001）。DAO和iMELD评分预
测HBV-ACLF患者预后的敏感性和特异度差异无统计学意义（P ＞ 0.05），均显著低于DAO + iMELD
评分（P ＜ 0.05）。结论 高水平DAO和iMELD评分是HBV-ACLF患者病死的独立危险因素；DAO联
合iMELD评分预测HBV-ACLF患者预后的特异度和敏感性较高，值得在临床中推广应用。
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Abstract: Objective To investigate the predictive value of plasma diamine oxidase (DAO) concentration
combined with iMELD score on short-term prognosis of hepatitis B virus-related acute-on-chronic liver
failure (HBV-ACLF). Methods Total of 98 cases with HBV-ACLF in Chongming Branch, Xinhua Hospital
Affiliated to School of Medicine, Shanghai Jiaotong University from August 2015 to December 2018 were
selected as HBV-ACLF group and 54 healthy people were enrolled as control group. Patients with HBV-
ACLF were divided into survival group (66 cases) and death group (32 cases) according to the prognosis after
1 month follow-up. Levels of plasma DAO concentration, total cholesterol (TC), triglyceride (TG), albumin
(ALB), total bilirubin (TBil), creatinine (SCr), serum sodium alanine aminotransferase (ALT), aspartate
aminotransferase (AST), prothrombin time (PT), prothrombin activity (PTA), MELD and iMELD scores
were calculated. The correlation between DAO, iMELD score and above indexes were analyzed by Pearson
correlation analysis. The risk factors of death of patients with HBV-ACLF were analyzed by multivariate
Logistic regression analysis. The values of DAO and iMELD score on predicting the prognosis of patients
with HBV-ACLF were analyzed by receiver operator characteristic (ROC) curve. Results The level of DAO
[(105.87 ± 44.76) ng/ml vs (8.65 ± 3.56) ng/ml] and iMELD score (44.63 ± 26.63 vs 4.54 ± 2.23) of patients
in HBV-ACLF group were higher than those in control group, the differences were statistically significant
(t = 21.376, 14.809; P ＜ 0.001). The level of DAO [(116.63 ± 33.54) ng/ml vs (79.65 ± 18.52) ng/ml] and
iMELD score (56.36 ± 16.63 vs 28.65 ± 13.24) of patients in death group were higher than those in survival
group, the differences were statistically significant (t = 23.654, 18.654; P ＜ 0.001). DAO and iMELD score
were positively correlated with AST, ALT, TBil, HBV DNA, TC and TG (r ＞ 0.4, P ＜ 0.05), and negatively
correlated with ALB and PTA (r ＜ -0.4, P ＜ 0.05). The incidence of ascites (53.8% vs 47.2%), the incidence
of liver and kidney syndrome (55.2% vs 57.1%), the incidence of liver cirrhosis (38.7% vs 44.2%), the incidence of hepatic
encephalopathy (43.6% vs 42.9%) and mortality (40.0% vs 42.9%) of HBV-ACLF patients with DAO ≥ 105.87 ng/ml
and iMELD score ≥ 44.63 were significantly higher than those with DAO ＜ 105.87 ng/ml and iMELD score ＜ 44.63,
the differences were statistically significant (all P ＜ 0.05). Levels of ALT [(390.21 ± 10.23) U/L vs (372.32 ± 10.54) U/L],
ALT [(452.32 ± 11.25) U/L vs (441.32 ± 9.65) U/L], HBV DNA [( 9.63 ± 2.45) copies/ml vs (5.96 ± 2.85) copies/ml],
TBil [(13654.36 ± 121.36) μmol/L vs (12065.36 ± 365.21) μmol/L], PT [(36.96 ± 5.54) s vs (25.63 ± 8.65) s],
PTA [(37.69 ± 5.48)% vs (57.65 ± 5.24)%], MELD score [(30.36 ± 5.45) points vs (24.63 ± 5.63) points], SCr
[(149.32 ± 3.25) μmmol/ L vs (142.32 ± 2.32) μmmol/L], DAO [(116.63 ± 33.54) ng/ml vs (79.65 ± 18.52) ng/ml]
and iMELD score [(56.36 ± 16.63) vs (28.65 ± 13.24)] of patients in death group were significantly higher
than those in survival group, ALB [(18.32 ± 3.52) g/L vs (26.54 ± 3.45) g/L] was significantly lower than that
in survival group, the differences were statistically significant (all P ＜ 0.05). Multivariate Logistic regression
analysis showed that DAO ≥ 105.87 ng/ml, iMELD score ≥ 44.63 and HBV DNA＞ 7.69 copies/ml
were independent risk factors for death of patients with HBV-ACLF (OR = 2.36, 2.48, 3.16; P ＜ 0.05). The
area under curve (AUC) of DAO + iMELD score, DAO and iMELD score were 0.834, 0.814 and 0.798,
respectively, the difference was statistically significant (z = 7.654, P ＜ 0.001), AUC of DAO and iMELD
score had no statistical significantly difference (z = 1.654, P = 0.074) and were significantly smaller than those of
DAO + iMELD score (z = 11.654, 10.905; P ＜ 0.001). Sensitivity and specificity of DAO and iMELD score had
no statistical significantly difference (P ＞ 0.05) and were significantly smaller than that of DAO + iMELD score (P ＜
0.05). Conclusions High levels of DAO and iMELD score are risk factors for adverse outcomes of patients
with HBV-ACLF. DAO combined with iMELD has high sensitivity and specificity in predicting the prognosis
of patients with HBV-ACLF, which is worthy of clinical application.
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