妊娠期肝病对围产儿的影响

目的探讨妊娠期肝病对围产儿的影响,如何预防或减少早产和新生儿窒息率,降低围产儿死亡率。方法对1995至2008年在本院收治并分娩的妊娠期肝病患者1802例及所分娩的新生儿进行回顾性分析。结果1802例妊娠期肝病中,妊娠合并病毒性肝炎1317例,其中以慢性肝炎最多见,占74.0%,其次是急性肝炎,占17.6%,重型肝炎占5.4%,肝炎肝硬化占3.0%。慢性肝炎的围产儿死亡率、新生儿窒息率和早产率分别为0.6%、10.1%和18.5%,重型肝炎分别为23.9%、49.3%和35.2%。重型肝炎与慢性肝炎相比,围产儿死亡率、新生儿窒息率和早产率显著升高（χ^2=41.64,P〈0.01;x^2=29.99,P〈0.01;χ^2=11.71,P〈0.01）。妊娠期特有肝病485例,占妊娠期肝病的18.4%,其中以妊娠期肝内胆汁淤积症（ICP）最多见（310例,占63.9%）,妊娠期急性脂肪肝（AFLP）14例,占2.9%。ICP中围产儿死亡率、新生儿窒息率和早产率分别为1.6%、36.8%和57.4%,AFLP中分别为21.4%、78.6%和85.7%。妊娠期急性脂肪肝与肝内胆汁淤积症相比,新生儿窒息率和早产率显著升高（χ^2=9.88,P〈0.01;χ^2=4.42,P〈0.05）。34例死亡围产儿的母亲中,乙型肝炎26例,占76.5%,其中重型乙型肝炎有17例,占65.4%。结论最常见的妊娠期肝病是病毒性慢性肝炎和妊娠期肝内胆汁淤积症,对围产儿危害最大的是妊娠合并重型肝炎和妊娠合并急性脂肪肝。     

病毒性肝炎——总论

妊娠期肝病分布特征与产科结局——蒋佩茹等（上海复旦大学附属上海市公共卫生中心妇产科201508）；《上海预防医学》，2006，18（2）：53．55【目的：了解妊娠期肝病的病因、临床类型的分布特征和产科结局。方法：对903例妊娠期肝病中属病毒性肝炎的病因构成及临床类型构成、妊娠期特有肝病类型构成、妊娠期肝病的产后结局进行统计分析。结果：903病例中，妊娠期合并病毒性肝炎672例，占74．4％；妊娠期特有的肝病23l例，占25．6％。妊娠期合并病毒性肝炎的病因以乙型肝炎最多见，占59．2％，乙型肝炎病毒携带状态占18．9％。妊娠期合并病毒性肝炎的临床类型以慢性肝炎最常见，占42．9％。妊娠期特有肝病的类型以妊娠期肝内胆汁淤积症OCP）最多见。急性肝炎围生儿死亡率、新生儿窒息率和早产率分别为2．3％、29．3％和24．8％，慢性肝炎分别为3．1％、17．8％和19．9％。ICP围生儿死亡率、新生儿窒息率和早产率分别为0．00％、l7．8％和20．0％，妊娠期合并重症肝病对产妇病死率的影响不大于非孕妇。结论：妊娠期病毒性肝炎病因以乙型肝炎多见，临床类型以慢性肝炎多见；妊娠期特有肝病以ICP多见。妊娠期肝病对围生儿死亡率、新生儿窒息率和早产率有影响，但妊娠和分娩对妊娠期肝病无显影响。】     

妊娠期肝病183例分析

分析 18 3例妊娠期肝病的病因、孕期情况及转归 ,探讨如何加强孕期保健及改善妊娠期肝病患者母儿预后的方法。结果 :妊娠各期合并病毒性肝炎 15 6例 ,与妊娠有关的肝病 2 7例 ;孕产妇死亡 2例 ,胎死宫内 4例 ;孕产妇出现肝性脑病、肾功能不全、弥散性血管内凝血、严重感染及产后出血等严重并发症 ,结论 :病毒性肝炎仍是妊娠期肝病的主要病因 ,妊娠急性脂肪肝 (AFL P)、妊娠特发性黄疸与妊高症是危害母婴健康的重要病因。婚前乙肝疫苗接种及注意个人卫生 ,孕期加强肝功能监测有助于减少妊娠期病毒性肝炎的发生 ;孕期将血清胆汁酸列为常规检查有助于早诊断、早治疗 ,减少母婴并发症 ;提高对 AFL P的认识 ,早期诊断 ,立即终止妊娠可改善 AFL P的预后     

妊娠急性脂肪肝Swansea诊断标准与国内诊断标准一致性研究

目的评价Swansea诊断标准与国内诊断标准对于妊娠急性脂肪肝(acutefattyliverof pregnancy,AFLP)患者诊断的一致性。方法回顾性分析首都医科大学附属北京地坛医院2008年1月至2018年1月收治的出院诊断为AFLP患者的资料,使用Swansea诊断标准进行评分。对同期收治的非AFLP妊娠期肝病(包括HELLP综合征、妊娠合并脂肪肝、妊娠期肝内胆汁淤积症、妊娠合并其他肝功能衰竭)患者进行Swansea诊断标准评分,并使用国内诊断标准进行判定。对Swansea诊断标准与国内诊断标准进行Kappa一致性检验,计算Swansea诊断标准的受试者工作特征曲线(receiver operating characteristic curve,ROC)下面积。结果出院诊断为AFLP的患者74例,HELLP综合征14例,妊娠合并脂肪肝87例,妊娠期肝内胆汁淤积症220例,妊娠合并其他肝功能衰竭9例。因74例患者中仅4例进行了肝组织活检,故以Swansea评分≥5分作为判定标准。出院诊断为AFLP的患者中,按照Swansea标准诊断AFLP 68例,非AFLP妊娠期肝病6例。非AFLP妊娠期肝病患者共计330例,按照Swansea标准诊断AFLP 13例,非AFLP妊娠期肝病317例。Swansea诊断与国内诊断标准一致性的Kappa值为0.848,ROC曲线下面积为0.940(95%CI:0.902～0.978)。结论 Swansea诊断标准与国内诊断标准诊断AFLP的一致性较好,可在临床中推广应用。     

妊娠期病毒性肝炎

妊娠期病毒性肝炎是指妊娠期间感染各型肝炎病毒而出现急性肝炎的临床表现。由于妊娠妇女的新陈代谢旺盛,肝脏负担加重。当妊娠中毒症时又可出现全身小动脉痉挛,使肝实质缺血、缺氧。因而,在妊娠期中特别在后期感染病毒性肝炎,病情常较严重,易发展为重症肝炎。这里略谈几点主要问题,供大家参考。一、发病率一般认为妊娠期并发病毒性肝炎较健康人群为高,据报告其发生率为非孕妇的5.9～8倍,约占妊娠人数0.025～0.08%。其中64%发生在妊娠早期;36%为中、后期。据Schiff报告在妊娠期黄疸中,病毒性肝炎约占40%,国内报告可高达     

姙娠合并急性黄色肝萎缩两例报告

本院自1954年7月至1959年7月底,五年中内科住院传染性肝炎患者共151人,共中4例急性黄色肝萎缩,皆为女性,两例与妊娠有关。急性黄色肝萎缩占我院传染性肝炎2.6％;在同时期产科分娩总数共5529,产科急性黄色肝萎缩发病率为3.6％。在妊娠期,传染性肝炎较非妊娠者易转变成急性黄色肝萎缩,这又与妊娠中毒症有关。本报告第二例有子癎前期的征象,患者在妊娠中毒症或肝脏有损害的基础上,再合并传染性肝炎,则易于转变为急     

中国妇女妊娠期肝异常的常见病因及对妊娠结局的影响Meta分析

目的分析中国妇女妊娠期肝异常的常见病因及对母婴结局的影响.方法计算机检索中国知网,万方数据库,维普数据库,收集中国近20年间发表的关于妊娠期肝异常的所有文献.并采用R软件、Stata软件进行数据的Meta分析.结果最终纳入37篇研究文献,累计病例共计8367例.Meta分析结果显示中国妇女妊娠期肝异常的常见病因构成比(95%CI)为:肝炎39%(30%-48%),妊娠高血压综合征17%(10%-25%),妊娠性肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)17%(14%-19%),妊娠期急性脂肪肝(AFLP)3%(2%-4%),妊娠剧吐8%(6%-11%),HELLP综合征3%(1%-5%).其中由肝炎引起的妊娠期肝异常的妊娠结局中,孕妇早产、剖宫产、产后出血的概率分别为20%、35%、15%;胎儿窘迫、围产儿死亡的概率分别为26%、16%;妊娠高血压综合征引起的妊娠期肝功能异常中,孕妇早产、剖宫产、产后出血的概率分别为21%、62%、16%;胎儿窘迫、围产儿死亡的概率分别为40%、15%;由妊娠性ICP引起的妊娠期肝功能异常中孕妇早产、剖宫产、产后出血的概率分别为36%、70%、15%,胎儿窘迫、围产儿死亡的概率分别为35%、16%.并且妊娠期肝异常与不良妊娠结局显著相关,其OR值(95%CI)分别为:早产4.48(3.89-6.60),剖宫产3.75(3.28-4.29),产后出血5.36(4.07-7.05),胎儿窘迫3.78(3.16-4.53),围产儿死亡6.39(3.27-12.49),妊娠期高血压4.67(3.44-6.35),新生儿窒息3.07(2.18-4.32).结论肝炎是引起妊娠期肝功能异常的首要病因,其次为妊娠高血压综合征、妊娠性肝内胆汁淤积症;并且均可不同程度增加妊娠及分娩时母婴风险.     

肝内胆汁淤积的预后

肝内胆汁淤积可发生于各种原因所致的肝脏疾病,例如发生于各型病毒性肝炎、原发性胆汁性肝硬化、药物性肝炎,妊娠末期肝内胆汁淤积、胆管癌等,其预后与其原发病有关。病毒性肝炎各个临床型,包括急性、慢性和重症肝炎均可发生肝内胆汁淤积。由于病毒性肝炎肝组织     

妊娠合并肝病的产科处理

妊娠期肝病对孕产妇及围产儿均有威胁,其中以妊娠合并病毒性肝炎(包括甲型、乙型和非甲非乙型肝炎)多见。据报道,孕妇感染病毒性肝炎或原有肝病恶化的发生率为非孕妇的9倍,重症(暴发性)肝炎为非孕妇的65.5倍。本文重点讨论妊娠合并常见肝病的产科处理。 一、妊娠合并乙型肝炎的处理 妊娠合并乙型肝炎较多见,不仅可致流产、早产、死胎、死产、新生儿窒息等,还可通过乙肝     

92例药物性肝炎临床分析

目的提高对药物性肝炎的认识。方法对92例药物性肝炎的原因、发病规律及临床特征进行分析。结果西药致肝损害74例(80.43%),中药致肝损害18例(占19.57%)。HBsAg阳性42例,其中急性黄疸型肝炎19例占45.2%,重症肝炎8例占19.05%,死亡3例占7.1%。HBsAg阴性50例,其中急性黄疸性肝炎12例占24%,重症肝炎2例占4%,无死亡病例。结论引发药物性肝炎的致病因素和影响药物性肝炎的预后因素有药物种类、用药时间、联合用药、患者自身健康状况、是否合并乙肝病毒感染等。     

Acute fatty liver of pregnancy -- an underlying condition for herpes simplex type 2 fulminant hepatitis necessitating liver transplantation

The infrequent occurrence of herpes simplex virus (HSV) hepatitis in healthy women in comparison with the high prevalence of HSV infections suggests that, in addition to deranged immunity, an underlying condition in the liver might be necessary to develop HSV hepatitis. We report the case of a 28-year-old pregnant woman in the 28 (th) week of gestation. Following HSV type 2 infection of the uterine cervix, acute liver failure developed, necessitating urgent liver transplantation. In addition to fulminant HSV type 2 hepatitis, the explanted liver also showed the histological features of acute fatty liver of pregnancy. The presented case suggests a possible pathogenetic role of acute fatty liver of pregnancy in the development of fulminant HSV hepatitis following recurrent infection with HSV in healthy pregnant women. We believe that early histopathological diagnosis, followed by specific antiviral treatment and liver transplantation in selected patients may improve the clinical outcome of otherwise almost uniformly fatal HSV hepatitis.     

Viral Hepatitis and Intrahepatic Cholestasis of Pregnancy

Summary: Specific serological tests which are now available for the diagnosis of infection with hepatitis A and hepatitis B viruses, were used to distinguish viral hepatitis from other causes of liver disease in pregnancy. Forty-nine (51·6%) of 95 pregnant patients had viral hepatitis, 24 hepatitis A and 25 hepatitis B. The majority of patients (26 of 28) presenting before 22 weeks gestation had viral hepatitis. By contrast, 23 (34·3%) of the remaining 67 patients presenting with abnormal liver function tests at ≫ 22 weeks gestation, had viral hepatitis; the majority of the remainder had features compatible with intrahepatic cholestasis of pregnancy. Although there were significant clinical and biochemical differences between the two groups, accurate diagnosis was only possible by using specific virological tests.     

妊娠期病毒性肝炎临床特点分析

目的了解妊娠期病毒性肝炎的临床特点。方法回顾性分析2009年1月至2013年3月于广州市第八人民医院因病毒性肝炎住院的77例妊娠妇女的临床资料,分析肝炎病因、血清病毒学特点、肝损害程度与孕期的相关性。计量资料的组间比较采用Kruskal-Wallis H检验。结果病因:乙型肝炎多见,共72例(93.51%),有10.27%患者感染甲、乙或戊型肝炎病毒所致急性病毒性肝炎;肝损害程度:中度肝损害64例(83.12%),重度肝损害7例(9.09%),肝衰竭3例(3.90%);肝炎发作时孕期:妊娠早期16例(20.78%),妊娠中期49例(63.64%),妊娠晚期12例(15.58%);肝功能指标:总胆汁酸(TBA)、TBil、白蛋白(Alb)、ALT、AST、凝血酶原活动度(PTA)在HBeAg阳性和阴性患者间,以及在HBV DNA106IU/ml和HBV DNA≤106IU/ml患者间差异均无统计学意义(P0.05)。结论妊娠期病毒性肝炎主要由HBV引起,多数引起中度肝损害,重度肝损害或肝衰竭常发生于妊娠中晚期,因此育龄妇女妊娠期须注意防治慢性乙型肝炎。     

Aetiology and outcome of acute viral hepatitis in pregnancy

The aetiologic types of sporadic acute viral hepatitis in 169 pregnant women were compared with those of 70 non-pregnant women and 287 adult men. The majority of pregnant women (87.6%) came with acute hepatitis in the last trimester of pregnancy. Non-A, non-B (NANB) hepatitis accounted for 81.6% of hepatitis during pregnancy in comparison with 48.6% in non-pregnant women and 57.1% in adult men. Hepatitis A was extremely uncommon during pregnancy. Hepatitis B infection accounted for 17% of all cases in pregnant women compared with 45% in controls. Acute viral hepatitis in pregnancy had a poor outcome as assessed by maternal and/or fetal mortality (28.5%). The outcome was equally bad in hepatitis NANB and hepatitis B. Pregnant women generally had significantly lower immunoglobulin levels in comparison with non-pregnant women. In acute NANB hepatitis during pregnancy, serum IgG and IgM levels were lower and higher, respectively, compared with those in non-pregnant women and pregnant women with acute hepatitis B. It is suggested that an immune suppression during pregnancy might be responsible for increased susceptibility to acute NANB viral hepatitis, which, by itself, seems to induce only a transient acute phase IgM response.     

Glutathione S-transferase and liver function in intrahepatic cholestasis of pregnancy and pruritus gravidarum

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease associated with poor maternal and fetal outcome. The diagnosis is based on pruritus with abnormal liver function in the absence of other pathological conditions. However, pruritus in pregnancy is common, and it may be the only presenting feature in ICP. No reliable test currently exists that can discriminate between those women destined to develop ICP and those with the benign condition of pruritus gravidarum (PG). The purpose of this prospective study was to investigate longitudinally the serum concentration of glutathione S-transferase alpha (GSTA, a specific marker of hepatocellular integrity) and to compare this with the temporal profile of conventional liver function markers in women with ICP (n = 63), PG (n = 43), and normal pregnant controls (n = 26). Blood was sampled on at least 3 separate occasions between 16 weeks of gestation and 4 weeks postpartum. Serum concentrations of GSTA increased with gestation in ICP, being significantly higher from 24 (+/-2) weeks compared with controls (400% difference; 95% CI, 240%-734%; P < .001). GSTA was also higher in ICP versus PG (433% difference; 95% CI, 228%-790%; P < .001) throughout the gestational period studied. Significant differences in the ICP compared with control and PG groups were also found for total bile acids, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase. In conclusion, the measurement of GSTA provides a test of liver dysfunction that distinguishes women with ICP from those with PG. Additionally, on the basis of this study, reference ranges for biochemical markers of liver function require reevaluation in pregnancy.     

Clinical course and management of acute and chronic viral hepatitis during pregnancy

Pregnancy is a para‐physiologic condition, which usually evolves without any complications in the majority of women, even if in some circumstances moderate or severe clinical problems can also occur. Among complications occurring during the second and the third trimester very important are those considered as concurrent to pregnancy such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, HELLP syndrome and acute fatty liver of pregnancy. The liver diseases concurrent to pregnancy typically occur at specific times during the gestation and they may lead to significant maternal and foetal morbidity and mortality. Commonly, delivery of the foetus, even preterm, usually terminates the progression of these disorders. All chronic liver diseases, such as chronic viral hepatitis, autoimmune hepatitis, Wilson's disease, and cirrhosis of different aetiologies may cause liver damage, independently from pregnancy. In this review we will also comment the clinical implications of pregnancies occurring in women who received a orthotopic liver transplantation (OLT) Therefore, the management of immunosuppressive therapy before and after the delivery in women who received liver transplant is becoming a relevant clinical issue. Finally, we will focus on acute and chronic viral hepatitis occurring during pregnancy, on management of advanced liver disease and we will review the literature on the challenging issue regarding pregnancy and OLT.     

Abnormal steroid sulfate in plasma of women with intrahepatic cholestasis of pregnancy.

Concentrations of numerous sulfate steroids were checked in the plasma of 10 women in normal pregnancy (NP), 21 women with intrahepatic cholestasis of pregnancy (ICP) and 10 pregnant women suffering from viral hepatitis with jaundice (VHP). A considerable increase in 5 alpha pregnane and 5 beta pregnane 3 alpha, 20 alpha diols, mono- and disulfates and in 5 alpha pregnane 3 beta, 20 alpha diols disulfates was observed only in ICP and not in VHP. This observation permits us to hypothesize that these hormone changes can have a causative role in the pathogenesis of ICP.     

Neonatal effects of maternal antiphospholipid syndrome

Antiphospholipid antibodies (aPL) can impair the physiologic development of a fetus during pregnancy not only by causing thrombosis of the placental vessels, but also by directly binding throphoblast cells and modifying their functions. Consequently, the presence of aPL in pregnant women is linked to an increased rate of pregnancy complications. These include recurrent early miscarriages, late fetal losses, and hypertensive disorders of gestation. In this clinical setting, preeclampsia is usually early and severe and can be complicated by the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome). The close association between aPL and obstetric pathology supports the inclusion of these manifestations in the clinical classification criteria of antiphospholipid syndrome. About 30% of children born to mothers with aPL passively acquire these autoantibodies; fortunately, the occurrence of thrombosis seems extremely rare in these babies. The prospective ongoing studies of children born to antiphospholipid syndrome patients reassure us about their general good health; however, some data suggest that learning difficulties might occur, possibly related to in utero exposure to aPL.     

Identification of Matrix Metalloproteinase-2 and 9 as Biomarker of Intrahepatic Cholestasis of Pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a severe liver disease uniquely occurring during pregnancy. In this study we aimed to identify novel biomarker for the diagnosis of ICP in Chinese population. 50 healthy pregnant women, 50 mild ICP patients and 48 severe ICP patients were enrolled for this study. Liver function tests, including serum total bilirubin, direct bilirubin, alanine transami-nase, aspartate aminotransferase and cholyglycine, were performed in all participants. After an overnight fast serum levels of total bile acids (TBA), matrix metalloproteinase (MMP)-2 and MMP-9 were measured, and their correlation with liver function tests were analyzed. The observed increase in serum TBA in ICP patients was not statistically significant which made it unreliable for diagnosis of ICP in Chinese population. On the other hand, both MMP-2 and MMP-9 serum levels exhibited a progressive and significant elevation in mild and severe ICP patients compared with healthy pregnant women, which also positively correlated with liver function tests. Serum levels of both MMP-2 and MMP-9 could be reliably used as laboratory abnormalities for accurate diagnosis and sensitive grading of ICP in Chinese population.