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妊娠期HBV相关慢加急性肝衰竭的临床特征和转归
DOI: 10.3969/j.issn.1001-5256.2022.04.010
伦理学声明：本研究于2020年8月10日经上海市公共卫生临床中心伦理委员会审批，批号为2020-S179-01。
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。
作者贡献声明：纪留娟参与收集、分析数据及论文撰写；梅雪、袁伟、邹颖、刘玉参与修改论文；钱志平、王介非指导撰写论文并最后定稿。
Clinical features and prognosis of HBV-related acute-on-chronic liver failure in pregnancy
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摘要:
目的 探讨妊娠期HBV相关慢加急性肝衰竭(HBV-ACLF)患者的临床特征和转归。 方法 回顾性分析上海市公共卫生临床中心2008年6月—2020年7月收治的26例妊娠期HBV-ACLF患者的临床资料，包括年龄、发病孕周、产次、首发症状、入院时并发症、实验室指标(WBC、Hb、PLT、ALT、TBil、Alb、SCr、MELD评分、HBsAg、HBV DNA等)、腹部超声、分娩方式、胎儿情况、治疗措施、预后转归等。正态分布的计量资料2组间比较采用t检验；非正态分布的计量资料2组间比较采用Wilcoxon秩和检验；计数资料2组间比较采用χ2检验或Fisher精确检验。 结果 26例患者中8例均在发病后28 d内死亡，病死率达30.8%。经产妇22例，占84.6%，ACLF往往发生在妊娠晚期(20/26，76.9%)，平均发病孕周为(30.9±5.8)周。HBV-ACLF临床表现不典型，首发症状常为乏力、纳差(21/26，80.8%)和尿黄(19/26，73.1%)等。死亡组的TBil(Z=-2.056，P=0.041)、凝血酶原时间(Z=-2.362，P=0.016)、国际标准化比值(Z=-2.528，P=0.009)、MELD评分(Z=-2.223，P=0.026)、首发症状至诊断时间(t=-2.468，P=0.021)、HBV DNA水平(χ2=7.571，P=0.021)、肝性脑病严重程度(χ2=24.775，P＜0.001)、并发症发生率(χ2=5.951，P=0.042)显著高于存活组，而纤维蛋白原(Z=-2.667，P=0.006)、凝血酶原活动度(Z=-2.365，P=0.016)水平明显低于存活组。 结论 HBV-ACLF是妊娠晚期严重并发症，经产妇多见，短期病死率极高。其早期临床表现隐匿，高MELD评分、高病毒载量和并发症的出现往往提示预后不良。 Abstract:Objective To investigate the clinical features and prognosis of pregnant women with HBV-related acute-on-chronic liver failure (HBV-ACLF). Methods A retrospective analysis was performed for the clinical data of 26 pregnant women with HBV-ACLF who were admitted to Shanghai Public Health Clinical Center from June 2008 to July 2020, including age, gestational weeks at disease onset, parity, initial symptoms, complications on admission, laboratory markers [white blood cell count, hemoglobin, platelet count, alanine aminotransferase, total bilirubin (TBil), albumin, serum creatinine, Model for End-Stage Liver Disease (MELD) score, HBsAg, and HBV DNA], abdominal ultrasound, mode of delivery, fetus conditions, treatment measures, and prognosis. The t-test was used for comparison of normally distributed continuous data between two groups, and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test and the Fisher's exact test were used for comparison of categorical data between two groups. Results Among the 26 patients, 8 died within 28 days after disease onset, and the mortality rate reached 30.8%. There were 22 multiparous patients, accounting for 84.6%, and HBV-ACLF often occurred in the third trimester of pregnancy (20/26, 76.9%), with a mean gestational age of 30.9±5.8 weeks. HBV-ACLF often had atypical clinical manifestations, and initial symptoms included weakness, poor appetite (21/26, 80.8%), and yellow urine (19/26, 73.1%). Compared with the survival group, the death group had significantly higher levels of TBil (Z=-2.056, P=0.041), prothrombin time (Z=-2.362, P=0.016), international normalized ratio (Z=-2.528, P=0.009), and MELD score (Z=-2.223, P=0.026), a significantly longer time from initial symptom to diagnosis (Z=-2.468, P=0.021), significantly higher HBV DNA level (χ2=7.571, P=0.021), degree of hepatic encephalopathy (χ2=24.775, P < 0.001), and incidence rate of complications (χ2=5.951, P=0.042), and significantly lower levels of fibrinogen (Z=-2.667, P=0.006) and prothrombin time activity (Z=-2.365, P=0.016). Conclusion HBV-ACLF is a serious complication in the third trimester of pregnancy and is often observed in multiparous patients, with an extremely high short-term mortality. It often has atypical clinical manifestations in the early stage, and high MELD score, high viral load, and complications often indicate a poor prognosis. -
表 1 妊娠期HBV-ACLF存活组和死亡组患者的临床特征比较
Table 1. Comparison of clinical characteristics between HBV-ACLF survival group and death group during pregnancy
临床指标 存活组(n=18) 死亡组(n=8) 统计值 P值 年龄(岁) 28.0±4.0 29.0±3.5 t=-0.886 0.385 发病孕周(周) 30.2±6.2 32.5±5.0 t=-0.897 0.379 TBil(μmol/L) 216.1(181.4~262.7) 311.9(221.4~372.4) Z=-2.056 0.041 Alb(g/L) 28.3±2.6 26.5±3.0 t=1.608 0.121 SCr(μmol/L) 51.6(37.1~56.8) 49.0(43.0~54.7) Z=-0.222 0.849 PT(s) 24.3(21.6~30.4) 43.5(25.9~46.9) Z=-2.362 0.016 PTA(%) 33.5(24.8~40.8) 17.0(15.3~33.0) Z=-2.365 0.016 INR 2.2(1.9~3.0) 4.6(2.4~5.2) Z=-2.528 0.009 FIB(g/L) 1.7(1.5~2.1) 0.9(0.6~1.5) Z=-2.667 0.006 血糖(mmol/L) 4.6±1.4 4.2±1.7 t=0.672 0.508 WBC(×109/L) 13.8±6.7 16.9±7.9 t=-1.034 0.312 Hb(g/L) 116.3±20.8 116.4±21.5 t=-0.008 0.993 PLT(×109/L) 162.3±67.8 164.6±68.5 t=-0.081 0.936 MELD评分 18.8(15.7~25.5) 28.7(20.6~32.5) Z=-2.223 0.026 首发症状至诊断时间(d) 6.5±3.5 10.0±3.0 t=-2.468 0.021 首发症状至抗病毒时间(d) 9.5±4.5 11.5±3.0 t=-0.845 0.408 
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表 2 妊娠期HBV-ACLF并发症分析
Table 2. Analysis of HBV-ACLF complications during pregnancy
并发症 存活组(n=18) 死亡组(n=8) χ2值 P值 感染[例(%)] 10(55.6) 6(75.0) 0.066 腹水[例(%)] 5(27.8) 4(50.0) 0.382 急性肾损伤[例(%)] 3(16.7) 3(37.5) 0.330 产后出血[例(%)] 3(16.7) 2(25.0) 0.628 肝性脑病[例(%)] 24.775 ＜0.001 无 11(61.1) 0 Ⅰ~Ⅱ期 7(38.9) 0 Ⅲ~Ⅳ期 0 8(100.0) 并发症数目[例(%)] 5.951 0.042 无 4(22.2) 0 1~2种并发症 10(55.6) 2(25.0) ≥3种并发症 4(22.2) 6(75.0)
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表 3 妊娠期HBV-ACLF患者的母婴结局
Table 3. Maternal and infant outcomes of HBV-ACLF patients during pregnancy
母婴结局 存活(n=18) 死亡(n=8) χ2值 P值 孕妇 HBV DNA[例(%)] 7.571 0.021 ＜105 IU/mL 5(27.8) 1(12.5) 105~106 IU/mL 10(55.5) 1(12.5) ＞106 IU/mL 3(16.7) 6(75.0) HBeAg[例(%)] 0.216 阳性 10(55.6) 2(25.0) 阴性 8(44.4) 6(75.0) 生产方式[例(%)] 0.108 剖宫产 12(66.7) 5(62.5) 阴道分娩 6(33.3) 1(12.5) 未生产 0 2(25.0) 胎儿[例(%)] 21(80.8) 5(19.2) 10.301 0.002 足月儿(37~42周) 8(38.1) 0 早产儿(＜37周) 13(61.9) 2(40.0) 胎死宫内 0 3(60.0)
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