妊娠期HBV相关慢加急性肝衰竭的临床特征和转归

纪留娟; 梅雪; 袁伟; 邹颖; 刘玉; 王介非; 钱志平

doi:10.3969/j.issn.1001-5256.2022.04.010

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

上海市公共卫生临床中心，上海 201508

基金项目:

上海申康中心促进市级医院临床技能与临床创新能力三年行动计划项目 (SHDC2020CR1037B-004);

国家“十三五”科技重大专项 (2018ZX10725506-002);

上海市卫健委课题 (20184Y0058)

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。

详细信息

通信作者:
王介非，wangjiefei@shaphc.org

钱志平，qianzhiping@shaphc.org

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出版历程
- 收稿日期: 2021-09-13
- 录用日期: 2021-10-18
- 出版日期: 2022-04-20

Clinical features and prognosis of HBV-related acute-on-chronic liver failure in pregnancy

Shanghai Public Health Clinical Center Affiliated to Fudan University, Shanghai 201508, China

Research funding:

The Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support and Shanghai Hospital Development Center Funding (SHDC2020CR1037B-004);

National Science and Technology Major Project during the 13th Five-Year Plan Period (2018ZX10725506-002);

Project of Shanghai Municipal Health Commission (20184Y0058)

More Information

Corresponding author: WANG Jiefei, wangjiefei@shaphc.org(ORCID: 0000-0002-6283-5965); QIAN Zhiping, qianzhiping@shaphc.org(ORCID: 0000-0003-4641-3348)

摘要

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。
- 乙型肝炎病毒 /
- 慢加急性肝功能衰竭 /
- 妊娠并发症 /
- 体征和症状 /
- 预后
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.
- Hepatitis B Virus /
- Acute-On-Chronic Liver Failure /
- Pregnancy Complications /
- Signs And Symptoms /
- Prognosis

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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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