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(intrahepatic cholestasis of pregnancy,ICP)是妊娠期妇女特有的严重并发症之一,临床上以皮肤瘙痒和血清胆汁酸升高(＞10μmol/L)为主要特征,重症可伴有黄疸和肝酶升高,常发生于妊娠中晚期.分娩后ICP的临床症状和实验室异常指标常可自动恢复正常,对孕妇危害不...     

妊娠期肝内胆汁淤积症3种治疗方案的疗效比较

目的 :评估熊去氧胆酸 (UDCA)、地塞米松 (DX)或葡萄糖、维生素 C、肌苷、鲁米那联用治疗妊娠肝内胆汁淤积症 (ICP)的效果。方法 :4 8例患者 ,随机分成三组 :A组 U DCA 1g/ d,14天为 1个疗程 ;B组 DX 9m g/ d,10天后渐减量而停药 ;C组 10 %葡萄糖、维生素 C、肌苷、鲁米那联用 ,观察疗效。结果 :三组患者治疗后的瘙痒评分 ,AL T、AST明显下降 (P<0 .0 5 ) ,组间无显著差异 (P>0 .0 5 ) ;A组、B组 TBA显著下降 (P<0 .0 1) ,而 C组无明显改变 (P>0 .0 5 ) ;与 C组相比 ,AB两组胎儿窘迫、早产、羊水粪染的发生明显减少 (P<0 .0 5 )。除 A组有 1例过敏外 ,母儿均无毒副反应。结论 :U DCA和 DX是治疗 ICP安全、有效的药物 ;联用葡萄糖、维生素 C、肌苷、鲁米那对改善肝功能 ,减轻瘙痒有一定作用     

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)是一种妊娠期特有肝脏疾病,其临床特点包括瘙痒、肝酶和血清胆汁酸水平升高。ICP通常发生在妊娠晚期,并于分娩后迅速消失。ICP病因是多因素的,遗传、内分泌及环境因素在其发病机制中相互作用。ICP的孕产妇结局通常是良性的,而胎儿并发症如早产、羊水粪染、胎儿窘迫和突然的不可预测的胎儿宫内死亡导致围产儿发病率和死亡率显著增加。熊去氧胆酸是目前治疗ICP最安全有效的药物。ICP的管理主要包括孕产妇肝功能与血清胆汁酸水平的监测,同时还包括评估胎儿安全性,并在完成促胎肺成熟后决定适时分娩。本文根据最近的文献资料综述了ICP最新的研究进展。     

肝细胞转运体与妊娠期肝内胆汁淤积症

妊娠期肝内胆汁淤积症是妊娠期常见的并发症之一。其对妊娠妇女影响不大,主要危及胎儿,可致胎儿宫内窘迫、自发性早产、甚至无法预测的胎儿宫内死亡等。研究表明,妊娠期肝内胆汁淤积症的发生可能与肝细胞上特异的介导胆汁分泌的膜转运蛋白(俗称肝细胞转运体)的损伤有关。对肝细胞转运体的研究,不仅对妊娠期肝内胆汁淤积症的病因及发病机制有进一步的认识,同时也可能为其治疗提供新的靶点与策略。     

肝细胞转运体与妊娠期肝内胆汁淤积症

妊娠期肝内胆汁淤积症是妊娠期常见的并发症之一.其对妊娠妇女影响不大.主要危及胎儿,可致胎儿宫内窘迫、自发性早产、甚至无法预测的胎儿宫内死亡等.研究表明,妊娠期肝内胆汁淤积症的发生可能与肝细胞上特异的介导胆汁分泌的膜转运蛋白(俗称肝细胞转运体)的损伤有关.对肝细胞转运体的研究,不仅对妊娠期肝内胆汁淤积症的病因及发病机制有进一步的认识,同时也可能为其治疗提供新的靶点与策略.     

熊去氧胆酸对雌孕激素诱导的肝内胆汁淤积孕鼠血生化指标、肝脏病理及肝细胞膜ATP酶的影响

目的 :探讨熊去氧胆酸 (UDCA)的应用对雌、孕激素诱导的肝内胆汁淤积孕鼠血生化指标、肝脏病理以及肝细胞膜ATP酶的影响。方法 :建立妊娠肝内胆汁淤积动物模型 ,随机分为 :胆淤非治疗组、治疗组 ,设立对照组。应用比色法测定各组肝细胞膜ATP酶 ,应用光学和电子显微镜进行肝脏病理学检查。结果 :①治疗组与胆淤非治疗组比较 ,治疗组的丙氨酸转氨酶 (ALT)、门冬氨酸转氨酶 (AST)、总胆酸 (TBA)明显降低 (P <0 0 5 ) ,而对照组与治疗组之间无差异。②病理组织学检查 :胆淤非治疗组肝脏光镜下见肝细胞周围胆酸形成。对照组和治疗组肝脏电镜下毛细胆管不扩张 ,无高电子密度物沉积。③胆淤非治疗组Na+ K+ ATP酶与对照组相比明显降低 (P <0 0 5 ) ;治疗组Na+ K+ ATP酶与对照组相比无差异 ,但却明显高于胆淤非治疗组 (P <0 0 5 )。结论 :熊去氧胆酸可能是治疗妊娠肝内胆汁淤积的有效药物     

血清甘胆酸的测定在妊娠肝内胆汁淤积症中的诊断价值

妊娠肝内胆汁淤积症（ＩＣＰ）是妊娠期特有一种以皮肤瘙痒和胆汁淤积为特征的严重合并症,诊断本症主要依靠临床综合指标,其中血清甘胆酸（ＣＧ）的测定具有重要的诊断价值。我院自１９９７年４月至１９９８年６月收治ＩＣＰ３３例,占此期间分娩总数９０４例的３６５...     

妊娠期肝内胆汁淤积症的诊断与治疗

妊娠期肝内胆汁淤积症 (ｉｎｔｒａｈｅｐａｔｉｃｃｈｏｌｅｓｔａｓｉｓｏｆｐｒｅｇ ｎａｎｃｙ ,ＩＣＰ)是一种重要的妊娠并发症 ,临床上以皮肤瘙痒和胆汁淤积为特征 ,对孕妇预后良好 ,对胎儿有不良影响 ,可引起早产、胎儿窘迫及胎死宫内、死产等 ,使围生儿患病率及病死率增加。1　诊断1.1　临床表现ＩＣＰ在妊娠中、晚期出现瘙痒 ,或瘙痒与黄疸同时共存 ,分娩后迅速消失。1.1.1　瘙痒　瘙痒往往是首先出现的症状 ,常起于 2 8～32周 ,但亦有早至妊娠 12周者。通常最先发生在手掌和脚掌 ,然后逐步延及小腿、大腿、上肢、后背、前胸及腹部…     

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...     

妊高征及妊娠期肝内胆汁淤积症患者血浆肝素水平测定及其变化

目的　探讨妊娠晚期孕妇血浆肝素水平降低对妊高征、妊娠期肝内胆汁淤积症 (ICP)发生的影响。方法　对 1 999年 1 0月至 2 0 0 0年 1 0月 70例孕妇用生色法测定血浆肝素 ,并同时测定血小板数与血浆纤维蛋白原水平。其中妊高征组 2 0例、ICP组 2 0例、正常妊娠组 30例。随机选取 30例非孕妇女作对照组。结果　三组孕妇血浆肝素水平均明显低于对照组 (P <0 0 5 ) ,妊高征组显著性低于正常妊娠组和ICP组 (P <0 0 1 ) ;正常妊娠组血小板数量明显低于对照组 (P <0 0 1 ) ,但其与妊高征组及ICP组的比较差异均无显著性 (P >0 0 5 ) ;三组孕妇血浆纤维蛋白原水平均极显著性高于对照组 (P <0 0 1 )。结论　随着妊娠终止 ,血浆中肝素和血小板随之恢复至正常范围。而妊高征患者产后血浆肝素尚未达到正常水平范围 ,说明该病的病理生理变化与血浆中肝素水平降低可能有关     

Alpha-hydroxybutyrate dehydrogenase activity in intrahepatic cholestasis of pregnancy.

OBJECTIVES: Intrahepatic cholestasis of pregnancy (ICP) is associated with increased perinatal mortality and morbidity. Alpha-hydroxybutyrate dehydrogenase (alpha-HBDH) is an enzyme that originates in the cytoplasm of hepatocytes and can be detected in the serum. The aim of this study was to determine the characteristics of alpha-HBDH activity in ICP. METHODS: The study included 100 women in their third trimester of pregnancy, 58 of whom had ICP (the study group) and 42 were healthy (the control group); another group, 26 nonpregnant women, was also analyzed to follow changes in alpha-HBDH activity during pregnancy. The concentrations or activity of fractionated bilirubin; bile acids; total alkaline phosphatase; alanine and aspartate aminotransferases; total high-density and low-density lipoprotein cholesterol; triglycerides; total protein; and alpha-HBDH were assessed. RESULTS: The activity of serum alpha-HBDH is increased during the third trimester of pregnancies complicated by ICP, and it correlates positively with total and direct bilirubin concentration and total alkaline phosphatase activity. CONCLUSIONS: Alpha-hydroxybutyrate dehydrogenase serum activity seems to be another biochemical parameter useful in the assessment of ICP severity.     

妊娠期肝内胆汁淤积症分子机制研究进展

妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)是一种多基因遗传病,ICP的发生可能与ABCB11、ABCB4、ABCC2、ATP 8B1、TJP2等相关遗传基因的突变等有关。本文就ICP的国内外遗传学分子机制的研究进展作一综述,探索ICP发生的可能机制,旨在为下一步研究ICP的可能的基因调控网络提供参考方向。     

乙型肝炎病毒感染与妊娠肝内胆汁淤积症的相关性研究

目的　探讨无症状乙型肝炎病毒 (HBV)感染是否会影响妊娠肝内胆汁淤积症 (ICP)的发生率、病程及相关并发症。方法　 1997年 1月至 2 0 0 1年 7月对 76 5 1例孕妇进行乙型肝炎 (乙肝 )血清学测定 ,分析比较乙肝血清学HBV表面抗原 (HBsAg)、HBVe抗原 (HBeAg)及HBV核心抗体 (HBcAb)阳性孕妇与阴性孕妇其ICP发生、转归的相关性。结果　在有HBV感染的孕妇中其ICP的发生率明显高于无HBV感染的孕妇 (分别为 9 7%及 4 2 % ,P <0 0 0 1)。有HBV感染的孕妇发生ICP瘙痒症状的时间明显早于无HBV感染的孕妇 ,分别为( 2 8 8± 3 2 )周及 ( 32 1± 2 7)周 ,P <0 0 0 1。有HBV感染的ICP孕妇终止妊娠时间明显早于无HBV感染的ICP孕妇 ,分别为 ( 36 1± 0 9)周及 ( 37 8± 1 6 )周 ,P <0 0 0 1。在ICP组中有无HBV感染其早产发生率差异有非常显著性意义 ,分别为 2 9 5 %及 12 2 % ,P <0 0 0 1。ICP孕妇中有无HBV感染产后 2 4h内阴道出血量差异也有非常显著性意义 ,分别为 ( 335 0± 76 7)mL及 ( 2 78 0± 97 6 )mL ,P<0 0 0 1。结论　感染了HBV的孕妇其ICP的发生率增高 ,应加强对这些孕妇的孕期监护 ,并且积极防治早产及产后出血的发生。     

The role of genetic mutations in intrahepatic cholestasis of pregnancy

ObjectiveIntrahepatic cholestasis of pregnancy (ICP) is a liver disorder of pregnancy characterized by pruritus, elevated liver enzymes and fasting serum bile acids. Genetic predisposition has been suggested to play a role in its etiology and mutations in the ATP8B1(OMIM 1602397) (FIC1), ABCB11(OMIM 1603201) (BSEP), and ABCB4(OMIM 1171060) (MDR3) genes have been implicated.In the present study, we aimed to investigate the possible role of ATP8B1, ABCB11, and ABCB4 gene mutations in the patients with ICP.Materials and methodsA total of 25 patients who were diagnosed with ICP were included in the study. Genetic test results and mutation status of the patients as assessed by the next-generation sequencing technology were retrospectively retrieved from the hospital database.ResultsOf all patients, significant alterations in the ATP8B1 (n = 2), ABCB11 (n = 1), and ABCB4 (n = 7) genes were observed in 10 patients using the molecular analysis testing. All these alterations were heterozygous. Of these alterations, four were reported in the literature previously, while six were not. Using the in-silico parameters, there was a pathogenic alteration in the ABCB4 gene in one patient, while there was no clinically relevant alteration in the other gene mutations in the remaining nine patients.ConclusionConsidering the fact that the alterations were compatible with clinical presentations of the ICP patients and the incidence of these mutations is low in the general population, we believe that our study results are clinically relevant. Further molecular genetic tests in ICP patients and functional studies supporting the results would shed light into the clinical importance of these alterations.     

无症状乙肝病毒感染对妊娠期肝内胆汁淤积症妊娠结局影响的探讨

目的:探讨无症状乙肝病毒感染对妊娠期肝内胆汁淤积症(ICP)的发生率及妊娠结局的影响。方法:采用回顾性调查方法对乙肝病毒感染的ICP孕妇118例和无乙肝病毒感染的ICP孕妇478例进行对比分析,利用卡方检验进行统计学分析,观察乙肝病毒感染对ICP的发生率及妊娠结局的影响。结果:有乙肝病毒感染孕妇的妊娠期肝内胆汁淤积症ICP发生率明显高于无乙肝病毒感染的孕妇(P<0.01),前者出现瘙痒症状时间明显早于后者(P<0.01)。有乙肝病毒感染的ICP孕妇的早产发生率也高于无乙肝病毒感染的孕妇(P<0.01)。两组ICP孕妇产后24h阴道出血量差异有统计学意义(P<0.01)。结论:无症状乙肝病毒感染可以使ICP的发生率增高,易引起早产,因此应加强对这类患者的孕产期监护和治疗,保证母婴的健康和安全。     

妊娠肝内胆汁郁积症47例临床分析

血清胆酸显著升高是妊娠肝内胆汁郁积症的一项特征性指标。应用放免分析法测定47例患者的血清结合胆酸,平均20.58±11.32μmol/L,较对照组增加8.3～144.8倍。按胆酸低、中、高分为三组,分别与临床症状、肝功能、分娩方式和妊娠结局进行比较,发现高胆酸组病情重、发病早和分娩并发症多。说明测定血清胆酸对诊断本病、判断病情及预后和及时处理具有重要的参考价值。     

Perinatal outcomes with intrahepatic cholestasis of pregnancy in twin pregnancies

Objective: To describe perinatal outcomes of twin pregnancies complicated by intrahepatic cholestasis of pregnancy (ICP).

Methods: We conducted a retrospective cohort study of women delivered at a large tertiary obstetric center in Shanghai, China from January 2006 to May 2014. Delivery data were abstracted from medical records of all twin gestations delivered at the hospital.

Results: A total of 129/1922(6.7%) twin and 1190/92?273 singleton (1.3%) pregnancies were complicated by ICP. An increased risk of stillbirth among twin pregnancies was observed (3.9% and 0.8% in the ICP and non-ICP groups, respectively; aOR 5.75, 95% CI 2.00–16.6). Stillbirths with ICP and twins occurred between 33 and 35 weeks gestation compared to 36–38 weeks gestation among singletons. ICP in twins was also associated with an increased risk of preterm birth (<37 weeks) with an aOR of 4.17 (95% CI 2.47–7.04) and an aOR of 1.89 (95% CI 1.26–2.85) for delivery <35 weeks. Twin pregnancies complicated by ICP also had increased meconium staining of amniotic fluid and lower birth weight.

Conclusions: Twin pregnancies with ICP have significantly increased risks of adverse perinatal outcomes including stillbirth and preterm birth. Stillbirth occurs at an earlier gestational age in twin gestation compared to singletons, suggesting that earlier scheduled delivery should be considered in these women.