妊娠期肝内胆汁淤积症

妊娠期肝内胆汁淤积症徐先明综述庄依亮审校（上海医科大学妇产科医院）妊娠期肝内胆汁淤积症（Ｉｎｔｒａｈｅｐａｔｉｃｃｈｏｌｅｓｔａｓｉｓｏｆｐｒｅｇｎａｎｃｙ，ＩＣＰ）易引起早产和胎儿窘迫、死胎、死产，近年来受到产科医生的重视，被列为高危妊娠之一，目前...     

妊娠期肝内胆汁淤积症

妊娠期肝内胆汁淤积症患者由于有较高的围产儿患病率和死亡率,已被列为高危妊娠受到学者们的日益关注.本文就近几年有关其病因、病理变化、临床表现、实验室检查以及诊断和治疗方面研究进展进行综述.     

妊娠期肝内胆汁淤积症

妊娠期肝内胆汁淤积症患者由于有较高的围产儿患病率和死亡率,已被列为高危妊娠受到学者们的日益关注,本文就近几年有关其病因,病理变化。临床表现,实验室检查以及诊断和治疗方面研究进展进行综述。     

妊娠期肝内胆汁淤积症病因学研究进展

妊娠期肝内胆汁淤积症(ICP)为高危妊娠,是妊娠期特有疾病.临床上以妊娠中晚期母体皮肤瘙痒和血清胆汁酸升高为特征,与围生儿不良结局密切相关,ICP已逐步引起产科医师的重视.然而,ICP的病因学复杂,至今尚不完全清楚,有可能是遗传易感妇女体内生殖激素及其代谢产物造成胆汁淤积,环境因素及其他因素也有可能参与其发病,其发病原...     

妊娠期肝内胆汁淤积症61例临床分析

妊娠期肝内胆汁淤积症cy,ICP)是妊娠期重要的并发症,以妊娠期出现皮肤瘙痒、黄疸和胆汁淤积为特征,早产率及围产儿死亡率高.1999年4月至2000年3月我院收治ICP61例,占此期间分娩总数1985例的3.02%.现分析如下.1 资料与方法1.1 临床资料 1999年4月至2000年3月我院产前检查筛查出ICP孕妇61例,24～34岁,平均26.7岁,于妊娠早、中、晚期分别测定肝功能.随机分为A、B两组,A组30例,按常规以葡萄糖醛酸内酯(肝泰乐)、维生素B6、天门冬氨酸钾镁,支链氨基酸针剂保肝治疗,B组31例以腺苷蛋氨酸(思美泰)1000mg/d、还原型谷胱甘肽(古拉定)1200mg/d保肝治疗,两组所用的其他常规对症药物及处理均相同,观察用药2周后肝功能变化.所有数据采用t检验.     

妊娠期肝内胆汁淤积症128例临床分析

因妊娠期肝内胆汁淤积症（ｉｎｔｒɑｈｅｐɑｔｉｃｃｈｏｌｅｓｔɑｓｉｓｏｆｐｒｅｇｎɑｎｃｙ,ＩＣＰ）可引起早产,胎儿宫内窘迫（ＦＩＵＤ）,围产儿死亡（ｐｅｒｉｎɑｔɑｌｉｎｆɑｎｔｄｅɑｔｈ）及产后出血,受到产科医生的重视。现对１９９１年１月１日至...     

妊娠期肝内胆汁淤积症胎盘病理的研究

妊娠期肝内胆汁淤积症胎盘病理的研究上海市第六人民医院妇产科病理研究室（２００２３３）刘伯宁有关妊娠期肝内胆汁淤积症（ｉｎｔｒａｈｅｐａｔｉｃｃｈｏｌｅｓｔａｓｉｓｏｆｐｒｅｇｎａｎｃｙ，ＩＣＰ）胎盘病理的研究较少，虽曾有文献报道在ＩＣＰ胎盘中，发现...     

妊娠期肝内胆汁淤积症的研究进展

妊娠期肝内胆汁淤积症（ICP）是妊娠中、晚期特发性肝脏疾病。由于血清胆汁酸升高,在临床上表现为以皮肤瘙痒和黄疸为特征,主要危害胎儿,出现胎儿窘迫、死胎、早产及其他新生儿并发症。ICP的病因和发病机制尚不明确。本文从遗传、激素和环境因素方面探讨了ICP的发病机制,通过胆汁酸对胎儿的影响,了解其对胎儿危害的机制,为临床上治疗ICP奠定基础。     

202例妊娠期肝内胆汁淤积症的妊娠结局分析

妊娠期肝内胆汁淤积症(intrahepatic cholestasisof pregnancy,ICP)是以妊娠中、晚期出现的皮肤搔痒、黄疸为特发症状的妊娠期特有疾病,可导致早产、羊水胎粪污染及围生儿死亡,是围生儿预后不良的重要原因。其不良妊娠结局已引起产科医师的广泛重视。通过对病例的回顾性分析,我     

妊娠期肝内胆汁淤积症发生死胎的临床因素分析

目的 探讨妊娠期肝内胆汁淤积症(ICP)孕妇发生胎儿死亡的临床特点、实验室指标及胎儿监护手段.方法 对1999年1月至2010年12月浙江大学医学院附属妇产科医院收治的发生死胎的21例ICP孕妇的临床资料进行回顾性分析.结果 (1)21例ICP孕妇的平均年龄(30.2±4.6)岁,其中＞35岁者4例;经产妇6例,1例2年前因ICP发生死胎而引产1次;20例单胎妊娠,1例双胎妊娠.(2)21例ICP孕妇的死胎均发生在孕晚期,胎儿死亡的孕周为29～41周,平均(33.8±4.2)周.12例发生在孕29～37周,9例发生在孕37周后.9例为门诊B超检查时确诊胎死宫内;9例因诊断ICP入院治疗期间发生胎心消失;2例临产后胎心消失;1例胎心监护提示V型减速,拟行急诊刮宫产术于麻醉期间胎心消失.在所有ICP孕妇中围产儿死亡率为0.148%(21/14 184).(3)21例ICP孕妇均有皮肤瘙痒,其中11例有全身皮肤瘙痒.10例在发生死胎前自觉胎动减少或消失.21例ICP孕妇血清甘胆酸水平均升高,其中21.49～64.48 μmol/L 11例,t≥64.48 μmol/L 10例.血清总胆汁酸水平升高16例(另5例未检查),最高达270μmoL/L.血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平升高14例,总胆红素＞21μmol/L 7例,直接胆红素升高12例.21例ICP孕妇中,重度15例,轻度6例.(4)9例孕妇门诊即确诊宫内死胎未做胎心监护,其余12例住院检查结果 为:胎心监护结果 可疑2例,无应激试验(NST)提示胎心轻度V型减速1例,B超提示脐动脉舒张期血流缺如3例,胎儿生物物理指标评分低值1例.(5)21例ICP孕妇均经阴道分娩.6例为自然宫缩娩出死胎,其余15例予米非司酮配合依沙吖啶羊膜腔注射或缩宫素引产,14例在48 h内成功娩出死胎,仅1例追加地诺前列酮栓后引产成功.所有死胎外观无异常,脐带长度均在正常范围,有4例脐带绕颈或绕体.胎盘胎膜外观无异常,18例羊水Ⅲ度胎粪污染,2例合并羊水过少.10例行死胎及胎盘病理检查,其中1例合并多发畸形,其余死胎病理检查未见明显异常,10例胎盘病理检查均有绒毛膜周围或底蜕膜、大血管周围的纤维蛋白沉积,同时伴有钙化、退行性变、红色梗死及局灶性合体细胞结节增多.结论 ICP孕妇发生死胎的孕周常在孕晚期,时间常在正常宫缩后,ICP重度可能是发生死胎的关键因素;尚无有效的胎儿监护指标可预测死胎的发生.因此,应综合评估病情,加强胎儿监护,适时终止妊娠.

Abstract：

Objective To investigate the clinical features,critical laboratory parameters,and fetal monitoring methods in intrahepatic cholestasis of pregnancy(ICP).Methods A retrospective analysis of 21 cases of ICP suffered with fetal death in Women's hospital.School of Medicine.Zhejiang University from January 1999 to December 2010 were discussed.Results(1)The average age of ICP patients suffered with fetal death were(30.2±4.6)years old.Among them,4 cases were older than 35 years,six cases were multipara.oneo of them suffered stillbirth 2 year before.Twenty cases were singleton pregnancies and 1 cage was twin pregnancy.(2)All 21 cases of fetal death occurred in the third trimester,12 cases occurred before 37 weeks,9 cases after 37 weeks.Nine cases were diagnosed by ultrasound in outpatient clinics,fetal heart beat disappeared in 9 patients after admission because of ICP, two disappeared after labor, one during anesthesia before emergent surgery. Perinatal mortality rate of ICP was 0. 148% (21/14 184), and fetal death occurred from 29 to 41 weeks with an average gestational age of ( 33.8 ± 4. 2 ) weeks, ( 3 ) Puritus occurred in all 21 cases while 11 of them had pruritus all over the body. Ten pregnant women felt the fetal movement decreased or disappeared before diagnosis of fetal death. The glycocholic acid levels increased in all of the 21 cases. Among them, glycocholic acid levels in 11 cases were (21.49 -64. 48) μmol/L, while in 10 cases were ≥64. 48 μmol/L Serum bile acid levels elevated in 16 cases which had been analyzed ( the other 5 cases had not been checked ), and the highest level reached 270 μmol/L Serum alanine aminotransferase and aspartate aminotransferase were increased in 14 cases. Seven cases had their total bilirubin ＞21 μmoL/L, and 12 cases had their direct bilirubin levels significantly elevated. Among the 21 cases of ICP, 15 cases were in severe status, while the other 6 cases were mild. (4) Nine patients had no antepartum surveillance since fetal death were diagnosed before admission. The results of antepartum surveillance were as follows: 2 cases had nonreassuring nonstress test (NST), one had mild "V" type deceleration. Absence of diastolic flow in umbilical artery were found in 3 cases, and low fetal biophysical score was got in one case. ( 5 ) All 21 patients had vaginal delivery. Six of them delivered after natural contraction, and the remaining 14 cases delivered after oral intake of mifepristone and amniotic injection of ethacridine, or oxytocin induced labor within 48 hours, only one case delivered after additional dinoprostone suppositories. The appearance of fetus, placentas and membranes were normal, the lengths of umbilical cord were average. Four cases were found with cords binding the necks or the bodies. Eighteen cases had grade Ⅲ amniotic fluid with meconium-stained, and 2 cases complicated by oligohydramnios. Ten cases had their fetuses and placentas examined by pathologist. Among them, one case had multiple malformations, no more obvious pathological abnormalities were found in other fetuses. Pathologic examination showed that fibrin deposited around chorion and deciduas basalis, large vessels accompanied by calcification, degeneration,hemorrhagic infarction, and increased focal syncytial nodules could be seen in all of the ten placentas. Conclusions Fetal death in pregnant women with ICP of ten occurs after the contractions, Severe ICP may be a key factor that involved in the occurrence of fetal death. Up to now, there is no valid indicators in fetal monitoring, which can predict fetal death. Extensive assessment of the severity and careful antepartum surveillance should be achieved before timely termination of pregnancy.     

胎盘胆盐输出泵蛋白的表达及其与妊娠期肝内胆汁淤积症的关系

目的：探讨胎盘组织中胆盐输出泵（bile salt export pump,BSEP）的表达水平及其与妊娠期肝内胆汁淤积症（intrahepatic cholestasis of pregnancy,ICP）的关系。方法：选取2012年2月—2013年8月在苏州市立医院本部产科住院分娩的ICP孕妇30例作为研究组（ICP组）,同期分娩的健康妊娠晚期孕妇30例作为对照组,采用免疫组化（SP）法和蛋白质印迹（western blotting）法测定2组孕妇胎盘组织中BSEP蛋白的表达。结果：BSEP蛋白表达于胎盘滋养细胞的细胞质中。ICP患者胎盘组织BSEP的表达低于正常胎盘组织,差异有统计学意义[（0.197 7±0.111 8） vs. （0.616 0±0.384 9）,P＜0.001]。结论：BSEP蛋白在胎盘组织中表达的降低可能与ICP有关。     

近20年妊娠肝内胆汁瘀积症诊断及处理的变化

目的探讨近20年妊娠肝内胆汁瘀积症(ICP)发病率及诊断、处理方法的变化.方法按每5年为1个时间段回顾性分析我院1980年1月至1999年12月间240例ICP的诊治情况,结果①ICP的发病率由1980年至1984年的0.27%上升为1995年至1999年的5.37%(P＜0.05).②诊断技术的改进,诊断规范化,特别是胆酸升高为ICP的特异性生化指标,使ICP确诊时间提前,当胆酸升高＞40 mg/L时,羊水粪染率明显增加(P＜0.01).③虽ICP发病率明显上升,但胎儿宫内窘迫发生率并未随之增加(P＞0.05).④分娩方式由阴道分娩逐渐过渡到以剖宫产结束分娩(P＜0.01).虽剖宫产率明显增高,但产后出血发生率并未增加,新生儿窒息率明显下降.结论ICP发生率增高,诊断规范化,血清胆酸检查辅以肝功能检查,缩短了确诊时间,剖宫产术是目前ICP终止妊娠的主要手段.     

妊娠期肝内胆汁淤积症患者多药耐药3基因外显子8和12突变的研究

目的:研究多药耐药3(MDR3)基因外显子8和12突变与妊娠期肝内胆汁淤积症(ICP)的关系,探讨ICP的发生机制。方法:从29例ICP患者及32例正常孕妇的外周血中提取DNA,聚合酶链反应(PCR)扩增MDR3基因外显子8和12,对PCR产物进行DNA测序分析。结果:ICP患者和对照组PCR均扩增出目的片段,且存在多态性位点G711A及A1260G,两组的8号外显子基因型频率和12号外显子基因型频率比较,差异均有统计学意义(P<0.05,P<0.01)。结论:云南临沧地区ICP的发生可能与MDR3外显子8和12的突变有关。     

妊娠期肝内胆汁瘀积症血脂改变及其临床意义

目的　探讨妊娠期肝内胆汁瘀积症 (ICP)血脂变化的特点及其临床意义。　方法　收集 74例妊娠晚期 ICP患者和 71例正常孕妇空腹血清 ,测定其血脂和载脂蛋白 ,进行比较 ;并观察ICP血脂变化与肝功能异常、母婴并发症及妊娠结局的关系。　结果　 (1) ICP组总胆固醇、甘油三酯、低密度脂蛋白、极低密度脂蛋白及载脂蛋白 B分别为 (7.3± 1.6 )、(4.4± 1.6 )、(3.9± 1.8)、(2 .0± 0 .8)和 (1.7± 0 .3) mm ol/ L ,显著高于正常妊娠组 (5 .9± 1.0、3.4± 1.6、2 .9± 1.0、1.6± 0 .8)和(1.0± 0 .3) m m ol/ L,(P均 <0 .0 5 ) ,高密度脂蛋白为 (1.2± 0 .5 ) m m ol/ L,显著低于正常妊娠组 (1.6± 0 .4) mm ol/ L,(P<0 .0 5 ) ;(2 )如将 95 %正常妊娠妇女血脂数值作为正常值范围 ,把 ICP病例分成血脂正常和异常组 ,则 ICP中血脂异常组丙氨酸转氨酶和碱性磷酸酶水平 (190 .3± 15 7.5和 334 .4±147.4) u/ L高于血脂正常组 (12 9.9± 10 7.1)和 (2 81.6± 10 2 .9) u/ L ,(P<0 .0 5 ) ,其羊水污染、胎儿窘迫、早产及新生儿并发症发生率显著增高 ,产后出血及围产儿死亡亦有增多的趋势。　结论　 ICP患者血脂多有异常 ,能反映病情的严重性 ,应做为 ICP常规监测指标。     

乙炔雌二醇诱发孕鼠肝内胆汁淤积

目的 探讨乙炔雌二醇（ＥＥ）在妊娠期肝内胆汁淤积症（ＩＣＰ）发病中的作用。方法 选择孕１５ｄ的清洁级ＳＤ大鼠２０只,随机分为观察组和对照组,分别皮下注射ＥＥ的丙二醇溶液２．５ｍｇ／Ｋｇ＾－１．ｄ＾－１和１,２－丙二醇（ＰＧ）,连续５ｄ。两组分别在用药前及用药后３ｄ和５ｄ检测血谷丙转氨酶（ＡＬＴ）、谷草转氨酶（ＡＳＴ）、碱性磷酸酶（ＡＬＰ）、总胆酸（ＴＢＡ）、胆固醇（ＣＨＯ）和甘油三酯（ＴＧ）的变化     

远程胎儿监护网络用于妊娠肝内胆汁瘀积症晚期监测的价值

目的　探讨远程胎儿监护网络在妊娠肝内胆汁瘀积症 (intrahepatic cholestasis of preg-nancy,ICP)产前监测的临床价值。　方法　采用远程胎儿监护网络 ,对 5 4例 ICP孕妇进行产前无负荷试验 (NST)监测 (研究组 ) ,同期进行常规胎儿监护 (胎动计数和定期到医院进行 NST检查 )的 ICP孕妇 5 4例作为对照 (对照组 ) ,分析两组胎儿监护结果和围产儿结局。　结果　研究组 NST异常检出率 (36 .1% )较对照组 (2 7.2 % )明显增加 (P<0 .0 5 )。研究组 NST异常图形为变异减速、基线变异减少或消失和胎儿心率 (fetal heart rate,FHR)过缓的百分率分别为 4 4 .1%、13.8%和 9.2 % ,与对照组(分别为 2 1.3%、2 9.8%和 2 3.4 % )比较 ,差异均有显著性 (P<0 .0 5 )。研究组新生儿窒息和早产儿的发生率分别为 11.1%和 9.3% ,低于对照组的 2 7.8%和 2 4 .1% (P<0 .0 5 )。两组剖宫产率的差异无显著性 (P>0 .0 5 )。　结论　利用远程胎儿监护网络进行 ICP产前监测 ,可改善围产儿预后 ,是 ICP孕妇自我监护的新选择。     

妊娠肝内胆汁淤积症患者血硒及胎盘硒水平变化与胎盘组织学改变的关系

OBJECTIVE: To explore the effect of deficiency of blood selenium and placental selenium on the damage of histomorphology of the placentas in ICP. METHODS: We measured the selenium concentration by a catalytic polorographic method in blood and placenta and glutathione peroxidase (GSH-Px) activity by a 5,5'-dithionbis (2-nitrobenzoic acid) direct method in blood in 30 women with ICP (ICP group) and 30 normal pregnant women (control group). Furthermore, the features of the placentas (10 from control group and 10 from ICP group) pathologic changes were observed microscopically. RESULTS: (1) The selenium concentrations in blood (0.0389 +/- 0.0090) mg/L and placenta (0.3770 +/- 0.0964) mg/kg and the activity of GSH-Px (59.31 +/- 11.42) U in ICP group were found to be significantly lower than those in blood (0.0477 +/- 0.0094) mg/L and placenta (0.4554 +/- 0.0626) mg/kg and the activity of GSH-Px (68.48 +/- 10.47) U in control group, respectively (P < 0.002). (2) The activity of GSH-Px had a significant positive correlation with selenium concentration in blood in ICP group (r = 0.05498, P < 0.001) and in control group (r = 0.06234, P < 0.001). There was a positive correlation between blood and placental selenium concentrations in ICP group (r = 0.6473, P < 0.001). On the other hand, there was not correlation in women with normal pregnancies. (3) Placentas obtained from women with ICP had swelling and fibrinoid necrosis of villi, increasing number of syncytial sprouts, thickening of vasculo-syncytial membrane (VSM) and decreasing size of the intervillous space under light microscopy. Placentas from control group did not show the pathologic changes as mentioned above. CONCLUSIONS: As selenium constitutes the active part of GSH-Px, these results suggest that the placental selenium deficiency may lead to reduced placental GSH-Px activity and the antioxidative defence may have been defective which may be associated with the damage of histomorphology of the placentas in ICP.     

丁二磺酸腺苷蛋氨酸联合地塞米松对妊娠期肝内胆汁淤积症患者免疫功能及疗效的影响

目的：探讨丁二磺酸腺苷蛋氨酸联合地塞米松对妊娠期肝内胆汁淤积症（ＩＣＰ）患者免疫功能及疗效的影响。方法：选取2013年9月—2015年9月住院的ICP患者78例,将所有研究对象分为观察组与对照组,各39例,对照组采用丁二磺酸腺苷蛋氨酸治疗,观察组采用丁二磺酸腺苷蛋氨酸联用地塞米松联合治疗。比较2组治疗前后血清总胆汁酸（TBA）、总胆红素（TBIL）、直接胆红素（DBIL）、谷丙转氨酶（ALT）、谷草转氨酶（AST）、白细胞介素12（IL-12）及肿瘤坏死因子α（TNF-α）水平,比较2组产后胎盘组织中TNF-α的表达水平及治疗效果。结果：观察组的治疗效果优于对照组,妊娠结局与围生儿状况同样优于对照组（P＜0.05）。2组患者治疗后TBA、TBIL、ALT、AST及IL-12水平均明显下降（P＜0.05）,且观察组较对照组下降更明显（P＜0.05）。观察组DBIL、TNF-α及产后胎盘TNF-α水平均低于对照组,观察组各指标治疗前后差值均高于对照组（P＜0.05）。结论：丁二磺酸腺苷蛋氨酸联合地塞米松治疗ICP,在缓解患者临床体征、降低血胆汁酸及改善肝功能等方面有显著的临床效果,并可改善患者的免疫功能状态、妊娠结局及围生儿状况。     

孕妇静脉血及其新生儿脐血硒水平及谷胱甘肽过氧化物酶活性与妊娠肝内胆汁淤积症的关系

目的　探讨孕妇静脉血及其新生儿脐血硒水平及谷胱甘肽过氧化物酶 (GSH Px)活性与妊娠肝内胆汁淤积症 (ICP)的关系。方法　采用催化极谱法及 5 ,5 ' 二硫代双 (二硝基苯甲酸 )直接法检测健康未孕妇女 30例 (健康未孕组 )血硒水平及GSH Px活性 ;检测ICP孕妇 (ICP组 )和正常妊娠妇女 (正常妊娠组 )各 30例孕晚期及产后母血、脐血硒水平及母血、脐血GSH Px活性。结果　 (1)ICP组产前、后母血硒水平分别为 (0 .0 389± 0 .0 0 90 )mg/L和 (0 .0 46 3± 0 .0 0 92 )mg/L ,GSH Px活性分别为 (5 9.31± 11.42 )活力单位 (U)和 (6 8.12± 11.46 )U ,正常妊娠组产前、后母血硒水平分别为 (0 .0 477± 0 .0 0 94)mg/L和 (0 .0 5 10± 0 .0 0 93)mg/L ,GSH Px活性分别为 (6 8.48± 10 .47)U和 (72 .6 7±9.83)U ,两组比较 ,差异均有显著性 (P <0 .0 0 5 )。 (2 )ICP组脐血硒水平为 (0 .0 387± 0 .0 0 93)mg/L ,GSH Px活性为 (5 7.6 6± 12 .2 5 )U ,正常妊娠组脐血硒水平为 (0 .0 46 1± 0 .0 0 89)mg/L ,GSH Px活性为(6 7.46± 11.93)U ,两组比较 ,差异均有极显著性 (P <0 .0 0 5 )。 (3)血硒水平与GSH Px活性呈正相关(P <0 .0 0 1)。结论　ICP患者血硒水平降低 ,导致GSH Px活性下降 ,自由基形成 ,破坏了肝细胞膜