The liver in pregnancy: disease vs benign changes

Liver dysfunction in a pregnant woman may be caused by the pregnancy, it may be unrelated to the pregnancy, or it may be a chronic condition that existed before the pregnancy. In any case, the clinical clues of liver dysfunction in pregnancy are not specific, and certain "abnormalities" in liver function tests may represent benign changes of pregnancy. On the other hand, prompt recognition of the signs of liver disease in pregnant patients leads to timely management and may save the life of both mother and baby.     

Liver disease in pregnancy

Acute viral hepatitis is the most common cause of jaundice in pregnancy. The course of acute hepatitis is unaffected by pregnancy, except in patients with hepatitis E and disseminated herpes simplex infections, in which maternal and fetal mortality rates are significantly increased. Chronic hepatitis B or C infections may be transmitted to neonates; however, hepatitis B virus transmission is effectively prevented with perinatal hepatitis B vaccination and prophylaxis with hepatitis B immune globulin. Cholelithiasis occurs in 6 percent of pregnancies; complications can safely be treated with surgery. Women with chronic liver disease or cirrhosis exhibit a higher risk of fetal loss during pregnancy. Preeclampsia is associated with HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome, acute fatty liver of pregnancy, and hepatic infarction and rupture. These rare diseases result in increased maternal and fetal mortality. Treatment involves prompt delivery, whereupon the liver disease quickly reverses. Therapy with penicillamine, trientine, prednisone or azathioprine can be safely continued during pregnancy.     

妊娠期孕妇肝功能异常123例临床分析

目的探讨妊娠期孕妇肝功能异常的病因及对妊娠结局的影响。方法分析123例（占同期住院妊娠孕妇的2．45％）妊娠期肝功能异常病人的病因及预后情况。结果123例由妊娠相关因素引起的肝功能异常56例（占45．53％），非妊娠特异因素引起的肝功能异常45例（占36．59％），另22例孕妇（17．89％）肝功能异常无特定的原因。123例肝功能异常孕妇的临床诊断主要包括：妊娠剧吐9例，妊娠高血压综合征（PIH）18例，妊娠期肝内胆汁郁积症（ICP）28例．妊娠期急性脂肪肝1例，乙型肝炎（HB）35例，自身免疫性肝炎3例，脂肪性肝炎3例，甲、丙、戊型肝炎各1例，药物性肝炎1例。与妊娠相关的肝功能异常发生在孕中期（26．02％）和孕晚期（64．23％）相对多于孕早期（9．76％）。孕早期以妊娠剧吐为主。孕中、晚期以病毒性肝炎（HV）、ICP和PIH为多见。这部分病人的早产率、产后出血率、剖宫产率、胎儿宫内窘迫率有明显增加（P〈0．05）。结论乙型病毒性肝炎、妊娠期肝内胆汁郁积症、妊娠高血压综合征是引起妊娠期肝功能异常的主要原因，这些合并症均可不同程度地增加妊娠及分娩时母子的危险性。     

Pregnancy in Chronic Active Hepatitis

The outcome of pregnancy in chronic active hepatitis (CAH) wasstudied retrospectively, together with a survival analysis ofpatients and a comparison of fertility with that expected fromcontrols drawn from the normal Australian population. Clinicalrecords of 73 cases of CAH included 37 women who were potentiallyfertile (aged 15–45 years) and there were 30 pregnanciesamong 16 of these women. Hepatic and obstetric complicationsand the outcome for the foetus and the mother were comparedwith the results from 36 reports accumulated from the literature. The results showed an incremental increase in survival of patientswith CAH according to decade of diagnosis from 1950 and similarseverity of liver disease in those who did, or did not, becomepregnant. Fertility was reduced in patients with CAH. Relapseof CAH occurred during pregnancy in only two patients, hepaticcomplications were minimal, and there was no consistent patternof alteration in liver function; 12 of 16 mothers are alivefor a mean period of eight years after pregnancy. Obstetriccomplications Included urinary tract Infections (six), toxaemiaof pregnancy (nine) and prematurity (seven); of the 30 pregnancies,four were terminated on medical advice in the early years ofthe study, three ended in spontaneous abortion, and there werefour perinatal deaths giving a foetal loss rate of 33 per cent.Despite the maternal disease and use of prednisolone and azathioprineduring pregnancy, the single congenital abnormality was pyloricstenosis. We conclude that in CAH fertility is reduced but pregnancieswhich occur can proceed without detriment to the mother providedthat prednisolone treatment is maintained; that a higher thannormal foetal loss can be expected; and that babies may be bornprematurely but will be normal.     

Pregnancy-associated severe liver dysfunction

Determining the cause of liver disease in pregnancy can present a difficult challenge for clinicians. Minor elevations in aminotransferases may be a harbinger of life-threatening processes, such as acute fatty liver of pregnancy (AFLP) or hemolysis, elevated liver enzyme levels, low platelet count (HELLP) syndrome. Preeclampsia, HELLP syndrome, and AFLP form a spectrum of disease that ranges from involving mild symptoms to severe life-threatening multiorgan system dysfunction. They have been shown to be the primary causes of severe hepatic dysfunction during pregnancy. This article attempts to define the clinical and diagnostic features, pathophysiology, and treatment options of these diseases.     

Ectopic Pregnancy: A Growing Concern

Ectopic pregnancy rates have increased threefold since 1970. Ectopic pregnancy continues to be the leading cause of maternal death in the first trimester of pregnancy. The identification of clients with ectopic pregnancies may be difficult. In this article, risk factors, assessment techniques, and treatment strategies are reviewed. A questionnaire is included for use during pregnancy verification to identify those clients who may be at risk of having an ectopic pregnancy. The role of the nurse practitioner in providing comprehensive care is also addressed.     

Myeloid-derived suppressor cells are implicated in regulating permissiveness for tumor metastasis during mouse gestation

Metastasis depends on the ability of tumor cells to establish a relationship with the newly seeded tissue that is conducive to their survival and proliferation. However, the factors that render tissues permissive for metastatic tumor growth have yet to be fully elucidated. Breast tumors arising during pregnancy display early metastatic proclivity, raising the possibility that pregnancy may constitute a physiological condition of permissiveness for tumor dissemination. Here we have shown that during murine gestation, metastasis is enhanced regardless of tumor type, and that decreased NK cell activity is responsible for the observed increase in experimental metastasis. Gene expression changes in pregnant mouse lung and liver were shown to be similar to those detected in premetastatic sites and indicative of myeloid cell infiltration. Indeed, myeloid-derived suppressor cells (MDSCs) accumulated in pregnant mice and exerted an inhibitory effect on NK cell activity, providing a candidate mechanism for the enhanced metastatic tumor growth observed in gestant mice. Although the functions of MDSCs are not yet understood in the context of pregnancy, our observations suggest that they may represent a shared mechanism of immune suppression occurring during gestation and tumor growth.     

Pregnancy in chronic active hepatitis

The outcome of pregnancy in chronic active hepatitis (CAH) was studied retrospectively, together with a survival analysis of patients and a comparison of fertility with that expected from controls drawn from the normal Australian population. Clinical records of 73 cases of CAH included 37 women who were potentially fertile (aged 15-45 years) and there were 30 pregnancies among 16 of these women. Hepatic and obstetric complications and the outcome for the foetus and the mother were compared with the results from 36 reports accumulated from the literature. The results showed an incremental increase in survival of patients with CAH according to decade of diagnosis from 1950 and similar severity of liver disease in those who did, or did not, become pregnant. Fertility was reduced in patients with CAH. Relapse of CAH occurred during pregnancy in only two patients, hepatic complications were minimal, and there was no consistent pattern of alteration in liver function; 12 of 16 mothers are alive for a mean period of eight years after pregnancy. Obstetric complications included urinary tract infections (six), toxaemia of pregnancy (nine) and prematurity (seven); of the 30 pregnancies, four were terminated on medical advice in the early years of the study, three ended in spontaneous abortion, and there were four perinatal deaths giving a foetal loss rate of 33 per cent. Despite the maternal disease and use of prednisolone and azathioprine during pregnancy, the single congenital abnormality was pyloric stenosis. We conclude that in CAH fertility is reduced but pregnancies which occur can proceed without detriment to the mother provided that prednisolone treatment is maintained; that a higher than normal foetal loss can be expected; and that babies may be born prematurely but will be normal.     

Severe hepatic dysfunction in pregnancy

Acute liver disease in pregnancy may have fatal consequences. Pre-eclampsia, HELLP syndrome and acute fatty liver of pregnancy form a spectrum of disease that range from mild symptoms to severe life-threatening multi-organ dysfunction. Early recognition of signs and prognostic indicators may enable prompt referral to specialist centres providing the multidisciplinary support required to reduce maternal and perinatal morbidity and mortality. We review the common causes of acute hepatic failure associated with pregnancy, and current management practices.     

Clinical review: Special populations - critical illness and pregnancy

Critical illness is an uncommon but potentially devastating complication of pregnancy. The majority of pregnancy-related critical care admissions occur postpartum. Antenatally, the pregnant patient is more likely to be admitted with diseases non-specific to pregnancy, such as pneumonia. Pregnancy-specific diseases resulting in ICU admission include obstetric hemorrhage, pre-eclampsia/eclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, amniotic fluid embolus syndrome, acute fatty liver of pregnancy, and peripartum cardiomyopathy. Alternatively, critical illness may result from pregnancy-induced worsening of pre-existing diseases (for example, valvular heart disease, myasthenia gravis, and kidney disease). Pregnancy can also predispose women to diseases seen in the non-pregnant population, such as acute respiratory distress syndrome (for example, pneumonia and aspiration), sepsis (for example, chorioamnionitis and pyelonephritis) or pulmonary embolism. The pregnant patient may also develop conditions co-incidental to pregnancy such as trauma or appendicitis. Hemorrhage, particularly postpartum, and hypertensive disorders of pregnancy remain the most frequent indications for ICU admission. This review focuses on pregnancy-specific causes of critical illness. Management of the critically ill mother poses special challenges. The physiologic changes in pregnancy and the presence of a second, dependent, patient may necessitate adjustments to therapeutic and supportive strategies. The fetus is generally robust despite maternal illness, and therapeutically what is good for the mother is generally good for the fetus. For pregnancy-induced critical illnesses, delivery of the fetus helps resolve the disease process. Prognosis following pregnancy-related critical illness is generally better than for age-matched non-pregnant critically ill patients.     

Can acetaminophen excess result in maternal and fetal toxicity?

This is the third case reported of maternal acetaminophen overdose during pregnancy. Such overdose may be associated with maternal liver toxicity. Fetal hepatotoxicity may be seen in association with maternal hepatotoxicity. As a result, the infant's blood coagulation times may be prolonged, and intracranial hemorrhage at delivery is a concern. Our case shows such a complication after chronic exposure to acetaminophen.     

Hepatic disorders severely affected by pregnancy: medical and obstetric management

Hepatic disorders severely affected by pregnancy include choledochal cysts that can be compressed by the gravid uterus and potentially rupture; hepatic adenomas that exhibit accelerated growth because of hyperestrogenemia during pregnancy; acute intermittent porphyria that is exacerbated by increased female sex hormones during pregnancy; splenic artery aneurysms that can rupture during pregnancy because of compression by the gravid uterus; Budd-Chiari syndrome that is promoted by hyperestrogenemia; and hepatitis E and herpes simplex hepatitis that are particularly severe during pregnancy. Hepatic disorders unique to pregnancy include intrahepatic cholestasis of pregnancy; acute fatty liver of pregnancy; preeclampsia and eclampsia; and hemolysis, elevated liver function tests, and low platelet count (HELLP) syndrome. Most disorders uniquely related to pregnancy are treated by prompt fetal delivery as soon as the fetus is sufficiently mature.     

孕妇血清总胆汁酸测定的临床意义

目的 了解正常孕妇和妊娠期肝内胆汁淤积症（ICP）患者血清总胆汁酸水平。方法 检测ICP组、妊娠高血压疾病组（PIH）、正常孕妇以及正常未孕女性及男性组血清总胆汁酸（TBA）的水平,同时对ICP组其他肝功能相关指标也进行检测。结果 ICP组TBA水平较其他3组明显增高,而其他3组之间差异无显著性。ICP孕妇TBA与血清碱性磷酸酶（ALP）、γ-谷氨酰转肽酶（GGT）、直接胆红素（DBIL）的检测水平有良好的相关性;且TBA在灵敏度和特异性上均优于以上指标。结论 血清总胆汁酸的测定对孕妇胆汁淤积症的诊断、疗效评估以及预后判断均具有重要意义。     

Three-dimensional sonographic measurement of liver volume in the small-for-gestational-age fetus.

OBJECTIVE: To assess the growth of the fetal liver in normal pregnancies and to evaluate the ability of fetal liver volume measurement for prediction of small-for-gestational-age fetuses. METHODS: Three-dimensional sonographic examinations were performed on 14 appropriate-for-gestational-age and 10 small-for-gestational-age fetuses. Liver volume and liver length were measured every 2 weeks after 20 weeks' menstrual age until delivery. RESULTS: A curvilinear relationship was found between the menstrual age and liver volume (R2 = 88.4%; P < .0001), and a normal range of liver volume measurement for estimating the growth of the fetal liver during normal pregnancy was generated. Liver length was normal in 7 of 10 small-for-gestational-age fetuses, whereas liver volume values in all small-for-gestational-age fetuses were below normal ranges in the mid to late third trimester. CONCLUSIONS: Our findings suggest that liver volume may be a useful measurement for diagnosing small-for-gestational-age fetuses in the mid to late third trimester but that liver length may not be predictive. Further studies involving a larger sample size would be needed to confirm this suggestion.     

Acute liver failure caused by herpes simplex virus in a pregnant patient: Is there a potential role for therapeutic plasma exchange?

A young woman presented with a febrile illness in the third trimester of pregnancy. Laboratory investigation revealed severe acute hepatitis with thrombocytopenia and coagulopathy. Liver injury progressed despite emergent caesarian section and delivery of a healthy infant. Therefore, therapeutic plasma exchange (TPE) was performed on three consecutive days post‐partum for a presumed diagnosis of acute liver failure (ALF) associated with pregnancy due to hemolysis, elevated liver enzymes, and low platelets (HELLP) or acute fatty liver of pregnancy (AFLP). Treatment with TPE was followed by biochemical and clinical improvement but during her recovery herpes simplex virus type 2 (HSV‐2) infection was diagnosed serologically and confirmed histologically. Changes in the immune system during pregnancy make pregnant patients more susceptible to acute HSV hepatitis, HSV‐related ALF, and death. The disease is characterized by massive hepatic inflammation with hepatocyte necrosis, mediated by both direct viral cytotoxicity and the innate humoral immune response. TPE may have a therapeutic role in acute inflammatory disorders such as HSV hepatitis by reducing viral load and attenuating systemic inflammation and liver cell injury. Further investigation is needed to clarify this potential effect. The roles of vigilance, clinical suspicion, and currently accepted therapies are emphasized. J. Clin. Apheresis, 28:426–429, 2013. © 2013 Wiley Periodicals, Inc.     

Echogenicity of fetal lung and liver quantified by the grey-level histogram width.

Grey-level histogram width (GLHW) values of fetal lung and liver were studied in 52 healthy fetuses in 24 to 38 weeks of pregnancy, comparing them to the mean grey level (MGL), grey-level standard deviation (GLSD) and the coefficient of variation (GLCV). Fetal lung GLHW was larger in 30-38 weeks than at 24-29 weeks, but there was no change in liver GLHW. GLHW was smaller in fetal lung than in the liver in 24-29 weeks, with no difference in 30-38 weeks. The lung/liver GLHW ratios were less than 1 in 24-29 weeks, but they were 1 or more in 30-35 weeks. Both MGL of fetal lung and liver showed linear increases during pregnancy, but no difference was found between the two. Fetal lung GLSD tended to decrease during pregnancy. The GLCV values of fetal lung and liver decreased during pregnancy, and differed between 24-29 weeks and 30-38 weeks, whereas there was no difference between fetal lung and liver. The correlation coefficients of GLHW and MGL of fetal lung and liver to the weeks of pregnancy were moderate, and the coefficients of GLSD and GLCV to the weeks of pregnancy were small. In conclusion, quantitatively measured echogenicity of fetal lung increased in 30 or more weeks of pregnancy, and suggested antepartum changes of fetal lung tissue. The GLHW is reliable, because it was reproducible in various gain settings of various ultrasonic imaging devices. The MGL, GLSD and GLCV are less reliable, because the grey level varied by the gain changes among various machines.     

妊娠甲状腺功能亢进患者抗甲状腺药物治疗

妊娠合并甲状腺功能亢进(甲亢),尤其是临床甲亢易出现不良妊娠结局,包括子痫、流产、早产、妊娠期糖尿病、胎儿宫内生长受限等,严重威胁孕妇和后代健康。抗甲状腺药物(ATD)是此时治疗甲亢的首选方案,但是近年来研究发现甲巯咪唑和丙基硫氧嘧啶均有致畸作用,此外还可能引起肝损害等严重不良反应,但它们影响的程度不同。因此,如何合理给予ATD治疗妊娠合并甲亢对于保障孕妇和后代健康十分重要,特别应注意严格控制妊娠早期(6～10周)ATD的使用。     

Neurocritical care complications of pregnancy and puerperum

Neurocritical care complications of pregnancy and puerperum such as preeclampsia/eclampsia, hemolysis, elevated liver enzymes, low platelets syndrome, thrombotic thrombocytopenic purpura, seizures, ischemic and hemorrhagic stroke, postpartum angiopathy, cerebral sinus thrombosis, amniotic fluid emboli, choriocarcinoma, and acute fatty liver of pregnancy are rare but can be devastating. These conditions can present a challenge to physicians because pregnancy is a unique physiologic state, most therapeutic options available in the intensive care unit were not studied in pregnant patients, and in many situations, physicians need to deliver care to both the mother and the fetus, simultaneously. Timely recognition and management of critical neurologic complications of pregnancy/puerperum can be life saving for both the mother and fetus.