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HBV相关慢加急性肝衰竭患者短期预后的影响因素分析
DOI: 10.3969/j.issn.1001-5256.2021.01.012
利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突，特此声明。
作者贡献声明：刘晨瑞、李亚萍负责课题设计，资料分析，撰写论文；罗森、冯丹丹、吴凤萍参与收集数据，修改论文；翟嵩、党双锁负责拟定写作思路，指导撰写文章并最后定稿。
Influencing factors for the short-term prognosis of patients with HBV-related acute-on-chronic liver failure
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摘要:
目的 分析探究影响HBV相关慢加急性肝衰竭(HBV-ACLF)短期预后的危险因素。 方法 收集2009年1月—2019年12月西安交通大学第二附属医院收治的240例非肝移植HBV-ACLF患者的临床资料，按照入院后28 d和90 d存活情况进行分组(28 d:生存组164例，死亡组76例；90 d:生存组140例，死亡组100例)。收集患者发病诱因、肝功能指标、MELD评分、MELD-Na评分和出现的并发症等资料。计量资料用2组间比较采用Mann-Whithey U检验，计数资料2组间比较采用χ2检验。根据ROC曲线，计算ROC曲线下面积(AUC)，采用约登指数确定临界值，HBV-ACLF短期预后的危险因素分析采用logistic多因素回归分析。 结果 HBV-ACLF患者的诱因主要包括HBV自发激活(55.6%)、核苷类似物停药或耐药引起HBV激活(25.2%)等。依28 d存活情况分组，基线资料中年龄、PTA、NLR、血钠、MELD评分、MELD-Na评分、TBil水平2组间比较差异均有统计学意义(Z值分别为-2.400、-6.015、-5.070、-5.103、-5.044、-7.430、-6.637，P值均＜0.05)；依90 d生存情况分组，基线资料中年龄、PTA、NLR、血钠、MELD评分、MELD-Na评分、TBil、胆固醇水平2组间比较差异均有统计学意义(Z值分别为-2.205、-7.728、-3.335、-4.015、-6.053、-7.908、-6.655、-3.607，P值均＜0.05)。logistic多因素回归分析显示，TBil＞260.20 mmol/L、PTA＜24.8%、NLR＞5.63、血钠＜130.8 mmol/L、MELD＞17.84分、MELD-Na＞25.1分是影响患者28 d生存的独立危险因素[OR(95%CI)分别为4.572 (1.321~15.823)、8.934(3.026~26.374)、2.632(1.126~6.152)、27.467(6.113~123.423)、4.303(1.048~17.663)、3.453(1.614~7.387)，P值均＜0.05]；TBil＞260.20 mmol/L、PTA＜25.5%、血钠＜135.3 mmol/L、MELD＞17.84分、MELD-Na＞25.1分是影响患者90 d生存的独立危险因素[OR(95%CI)分别为5.148(1.918~13.822)、15.718(5.161~47.866)、10.080(3.244~31.323)、11.157(2.580~48.254)、4.391(2.057~9.372)，P值均＜0.05]。240例患者中160例(66.7%)90 d内发生感染，其中细菌感染140例、病毒感染12例，真菌感染8例。160例出现感染的患者其90 d病死率显著高于无感染的患者(46.3% vs 32.5%, χ2=6.720，P=0.010)。240例患者中176例28 d内出现腹水，44例出现胸腔积液，36例发生急性肾损伤，60例发生肝性脑病，12例发生消化道出血, 2组间急性肾损伤、Ⅲ~Ⅳ度肝性脑病、消化道出血所占比例比较差异均有统计学意义(χ2值分别为64.088、29.811、7.797, P值均＜0.05)。 结论 HBV-ACLF患者基线TBil、PTA、血钠、MELD评分、MELD-Na评分是影响患者28 d和90 d预后的独立危险因素。HBV激活引起的肝脏炎症坏死是ACLF的始动因素，而感染、急性肾损伤、肝性脑病和消化道出血是影响患者预后的主要的并发症。 Abstract:Objective To investigate the influencing factors for the short-term prognosis of patients with HBV-related acute-on-chronic liver failure (HBV-ACLF). Methods Clinical data were collected from 240 HBV-ACLF patients without liver transplantation who were admitted To The Second Affiliated Hospital of Xi'an Jiaotong University from January 2009 to December 2019, and the patients were divided into groups according to survival on days 28 and 90 after admission (28-day survival group with 164 patients and 28-day death group with 76 patients; 90-day survival group with 140 patients and 90-day death group with 100 patients). The data collected included predisposing factors, liver function parameters, Model for End-Stage Liver Disease (MELD) score, MELD combined with serum sodium concentration (MELD-Na) score, and complications. The Mann-Whitney U 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 receiver operating characteristic (ROC) curve was plotted to calculate the area under the ROC curve (AUC), and a multivariate logistic regression analysis was used to investigate the risk factors for the short-term prognosis of HBV-ACLF. Results The main predisposing factors of HBV-ACLF included spontaneous activation of HBV (55.6%) and HBV activation caused by the withdrawal of or resistance to nucleoside analogues (25.2%). There were significant differences in age, prothrombin time activity (PTA), neutrophil-lymphocyte ratio (NLR), serum sodium, MELD score, MELD-Na score, and total bilirubin (TBil) at baseline between the 28-day survival group and the 28-day death group (Z=-2.400, -6.015, -5.070, -5.103, -5.044, -7.430, and -6.637, all P < 0.05), and there were also significant differences in age, PTA, NLR, serum sodium, MELD score, MELD-Na, TBil, and cholesterol at baseline between the 90-day survival group and the 90-day death group (Z=-2.205, -7.728, -3.335, -4.015, -6.053, -7.908, -6.655, and -3.607, all P < 0.05). The multivariate logistic regression analysis showed that TBil > 260.20 mmol/L (odds ratio [OR]=4.572, 95% confidence interval [CI]: 1.321-15.823, P < 0.05), PTA < 24.8% (OR=8.934, 95%CI: 3.026-26.374, P < 0.05), NLR > 5.63 (OR=2.632, 95%CI: 1.126-6.152, P < 0.05), serum sodium < 130.8 mmol/L (OR=27.467, 95%CI: 6.113-123.423, P < 0.05), MELD score > 17.84 (OR=4.303, 95%CI: 1.048-17.663, P < 0.05), and MELD-Na score > 25.1 (OR=3.453, 95%CI: 1.614-7.387, P < 0.05) were independent risk factors for 28-day survival; TBil > 260.20 mmol/L (OR=5.148, 95%CI: 1.918-13.822, P < 0.05), PTA < 25.5% (OR=15.718, 95%CI: 5.161-47.866, P < 0.05), serum sodium < 135.3 mmol/L (OR=10.080, 95%CI: 3.244-31.323, P < 0.05), MELD score > 17.84 (OR=11.157, 95%CI: 2.580-48.254, P < 0.05), MELD-Na score > 25.1 (OR=4.391, 95%CI: 2.057-9.372, P < 0.05) were independent risk factors for 90-day survival. Among the 240 patients, 160 (66.7%) experienced infection within 90 days, among whom 140 had bacterial infection, 12 had viral infection, and 8 had fungal infection. The 160 patients with infection had a significantly higher 90-day mortality rate than the patients without infection (46.3% vs 32.5%, χ2=6.720, P=0.010). Of all 240 patients, 176 had ascites, 44 had pleural effusion, 36 had acute renal injury, 60 had hepatic encephalopathy, and 12 had gastrointestinal bleeding within 28 days, and there were significant differences in the proportion of patients with acute renal injury, grade Ⅲ-Ⅳ hepatic encephalopathy, or gastrointestinal bleeding between the 28-day survival group and the 28-day death group (χ2=64.088, 29.811, 7.797, all P < 0.05). Conclusion TBil, PTA, serum sodium, MELD score, and MELD-Na score at baseline are independent risk factors for the 28- and 90-day prognosis of HBV-ACLF. Liver inflammation and necrosis caused by HBV activation may be the initiating factor for ACLF, and infection, acute renal injury, hepatic encephalopathy, and gastrointestinal bleeding are the main complications affecting the prognosis of patients. -
Key words:
- Hepatitis B Virus /
- Acute-On-Chronic Liver Failure /
- Prognosis
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表 1 2组患者基线数据的比较(依28 d生存情况分组)
项目 生存组(n=164) 死亡组(n=76) 统计值 P值 年龄(岁) 49.00(32.00~54.00) 51.50(46.25~58.50) Z=-2.400 0.016 男/女(例) 120/44 60/16 χ2=0.924 0.336 PTA (%) 37.05(29.50~39.70) 21.90(18.53~32.10) Z=-6.015 ＜0.001 NLR 2.55(1.79~4.15) 5.42(3.02~8.09) Z=-5.070 ＜0.001 血钠(mmol/L) 137.20(134.40~139.10) 133.35(128.93~137.65) Z=-5.103 ＜0.001 MELD评分 18.14(15.25~22.00) 23.13(18.95~26.15) Z=-5.044 ＜0.001 MELD-Na评分 20.37(15.56~22.53) 27.62(23.14~33.42) Z=-7.430 ＜0.001 TBil (mmol/L) 242.25(228.50~311.90) 372.25(297.90~463.77) Z=-6.637 ＜0.001 血小板计数(109/L) 97.50(52.00~158.00) 100.00(55.75~139.25) Z=-0.464 0.643 SCr(μmol/L) 57.87(46.36~69.61) 59.05(48.23~71.59) Z=-0.464 0.643 胆固醇(mmol/L) 2.28(1.43~2.78) 1.94(1.46~2.29) Z=-1.232 0.218 AFP(ng/ml) 16.36(5.33~104.10) 30.06(5.44~571.23) Z=-1.645 0.100 
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表 2 2组患者基线数据的比较(依90 d生存情况分组)
项目 生存组(n=140) 死亡组(n=100) 统计值 P值 年龄(岁) 49.00(33.00~54.00) 51.00(43.00~57.00) Z=-2.205 0.027 男/女(例) 100/40 80/20 χ2=2.286 0.131 PTA(%) 38.20(33.50~39.80) 23.50(19.20~31.50) Z=-7.728 ＜0.001 NLR 2.64(1.87~4.94) 3.69(2.48~7.63) Z=-3.335 ＜0.001 血钠(mmol/L) 137.00(134.70~139.00) 133.40(130.20~139.50) Z=-4.015 ＜0.001 MELD评分 17.60(14.22~21.25) 22.00(20.15~26.01) Z=-6.053 ＜0.001 MELD-Na评分 18.56(15.25~22.40) 27.26(21.32~32.85) Z=-7.908 ＜0.001 TBil (mmol/L) 234.20(224.40~309.70) 343.06(277.92~442.55) Z=-6.655 ＜0.001 血小板计数(109/L) 102.00(57.00~151.00) 93.00(52.00~140.00) Z=-0.423 0.673 SCr(μmol/L) 58.33(48.24~69.61) 54.50(47.41~68.03) Z=-0.619 0.536 胆固醇(mmol/L) 2.33(1.53~2.91) 1.93(1.36~2.28) Z=-3.607 ＜0.001 AFP(ng/ml) 14.98(5.22~90.70) 41.52(7.12~248.70) Z=-1.881 0.060
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表 3 各指标的AUC和临界值(基于28 d、90 d生存情况)
指标 28 d 90 d AUC(95%CI) 临界值 P值 AUC(95%CI) 临界值 P值 TBil(mmol/L) 0.769(0.704~0.834) 260.2 ＜0.001 0.761(0.698~0.824) 260.2 ＜0.001 PTA(%) 0.732(0.661~0.803) 24.8 ＜0.001 0.781(0.720~0.842) 25.5 ＜0.001 NLR 0.705(0.633~0.777) 5.63 ＜0.001 0.611(0.536~0.686) 3.55 0.004 血钠(mmol/L) 0.720(0.646~0.795) 130.8 ＜0.001 0.660(0.582~0.738) 135.3 ＜0.001 MELD评分 0.705(0.636~0.774) 17.84 ＜0.001 0.735(0.671~0.799) 17.84 ＜0.001 MELD-Na评分 0.802(0.744~0.860) 25.1 ＜0.001 0.807(0.752~0.861) 25.1 ＜0.001
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表 4 HBV-ACLF患者基线数据与28 d预后的多因素分析
指标 OR(95%CI) P值 校正OR(95%CI) 校正P值 TBil＞260.2 mmol/L 10.861(4.905~24.048) ＜0.001 4.572(1.321~15.823) 0.016 PTA＜24.8% 10.278(5.183~20.382) ＜0.001 8.934(3.026~26.374) ＜0.001 NLR＞5.63 4.146(2.259~7.611) ＜0.001 2.632(1.126~6.152) 0.026 血钠＜130.8 mmol/L 14.182(6.099~32.978) ＜0.001 27.467(6.113~123.423) ＜0.001 MELD评分＞17.84 14.087(4.915~40.377) ＜0.001 4.303(1.048~17.663) 0.043 MELD-Na评分＞25.1 6.717(3.683~12.248) ＜0.001 3.453(1.614~7.387) ＜0.001
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表 5 HBV-ACLF患者基线数据与90 d预后的多因素分析
指标 OR(95%CI) P值 校正OR(95%CI) 校正P值 TBil＞260.2 mmol/L 12.410(6.201~24.836) ＜0.001 5.148(1.918~13.822) 0.001 PTA＜25.5% 21.000(9.290~47.471) ＜0.001 15.718(5.161~47.866) ＜0.001 NLR＞3.55 3.182(1.856~5.454) ＜0.001 1.066(0.443~2.563) 0.887 血钠＜135.3 mmol/L 3.879(2.255~6.671) ＜0.001 10.080(3.244~31.323) ＜0.001 MELD评分＞17.84 25.412(8.860~72.885) ＜0.001 11.157(2.580~48.254) 0.001 MELD-Na评分＞25.1 7.111(3.975~12.721) ＜0.001 4.391(2.057~9.372) ＜0.001
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表 6 HBV-ACLF患者并发症与28 d预后的关系
并发症 生存组(n=164) 死亡组(n=76) χ2值 P值 腹水[例(%)] 116(71) 60(79) 1.793 0.181 胸腔积液[例(%)] 28(17) 16(21) 0.549 0.459 急性肾损伤[例(%)] 4(2) 32(42) 64.088 ＜0.001 Ⅲ~Ⅳ度肝性脑病[例(%)] 8(5) 24(32) 29.811 ＜0.001 消化道出血[例(%)] 4(2) 8(11) 7.797 ＜0.001
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