Pregnancy and liver transplantation

To define the risks and outcomes associated with pregnancy and liver transplantation, we reviewed our experience in managing eight pregnant women who had undergone orthotopic liver transplantation. Seven patients conceived after transplantation; the interval from transplantation to conception ranged from 3 weeks to 24 months. One patient received an allograft at 26 weeks' gestation for hepatic failure secondary to acute fulminant hepatitis B. Of the seven patients who conceived after transplantation, six had live births and one electively terminated her pregnancy. Five patients developed worsening hypertension and/or preeclampsia. Three patients developed severe preeclampsia and required delivery. One patient suffered acute allograft rejection during pregnancy which was successfully treated with corticosteroids. Two patients had persistent elevation of serum transaminases and two had severe anemia. The mean gestational age at delivery was 32.8 weeks. Of the six live births to women who conceived after transplantation, five infants survived and are well and one infant died. There were no congenital anomalies. All mothers are alive at this time. Pregnancy in recipients of hepatic allografts is associated with good perinatal outcome, but there is an increased risk of preeclampsia, worsening hypertension, and preterm delivery. Pregnancy does not appear to have a deleterious effect on hepatic graft function or survival. Joint management of these patients by a transplant specialist and a perinatologist is essential.     

妊娠期肝脏疾病的临床特点分析

目的:探讨妇女妊娠后引发的肝脏疾病的特点。方法:对金华市区4所医院近6年内收治的1775例妊娠期肝脏疾病的临床特点进行回顾分析,前3年为A组(539例),后3年为B组(1236例)。比较两组临床表现和对孕产妇、胎儿的影响,并与同期住院的正常孕产妇(24590例)进行比较。结果:妊娠期肝内胆汁淤积症、皮肤瘙痒,B组较A组明显增加(P<0.05),而病毒性肝炎、妊娠剧吐、子痫前期、子痫所占比例有所下降(P<0.05)。与正常妊娠组比,肝病组胎膜早破、产后出血、弥散性血管内凝血、早产、流产、胎儿宫内窘迫、死胎、新生儿窒息、新生儿死亡均极显著地增加(P<0.01)。结论:近3年妊娠期肝脏疾病种类与前期有所不同;妊娠期肝病对孕产妇和胎儿有显著影响(P<0.05)。临床医生要高度重视,并进行有效的预防和治疗。     

Fulminant hepatitis A infection in second trimester of pregnancy requiring living-donor liver transplantation

We present an 18-year-old pregnant woman who was referred to our emergency clinic as a case of acute hepatic failure and hepatic encephalopathy. Laboratory tests showed abnormal liver function tests and serological workup was consistent with acute hepatitis A infection. Ultrasonography revealed a single live fetus with fetal biometry compatible with 18 gestational weeks. The patient underwent a highly urgent liver transplantation using a right lobe graft from her husband. Histological examination of the explanted liver showed acute, lymphocyte-rich, diffuse necrotizing hepatitis, consistent with acute necrotizing hepatitis A. After the operation her allograft function gradually recovered. Her follow-up obstetrics ultrasound revealed a male fetus with severely decreased amniotic fluid. The patient was informed about the poor prognosis of her pregnancy and the pregnancy was terminated by vaginal misoprostol induction. She has maintained a good general condition and liver function for 4 months postoperatively, up to the present time.     

Successful pregnancy after a liver transplant

The literature contains limited reports on successful pregnancy outcomes after a liver transplant. We report an uncomplicated pregnancy and delivery in a patient 35 months after liver transplantation because of chronic active hepatitis with resultant liver failure secondary to non-A non-B hepatitis.     

Overview of infection causing hepatitis other than non-A to E hepatitis virus during pregnancy

Abnormal liver function tests during pregnancy are common. While hepatic injury during pregnancy mostly has minimal adverse influence on maternal and fetal outcomes, severe maternal and fetal morbidities, and even death, sometimes occur. Here, we review the epidemiology, clinical features, diagnosis, and management of hepatitis during pregnancy caused by the less common pathogens, including Epstein–Barr virus (EBV), cytomegalovirus (CMV), herpes simplex viruses (HSVs), dengue fever, malaria, leptospirosis, Q fever, typhoid fever, and other occasional infections, as well as the implications on breastfeeding of the infants. Hepatitis during pregnancy with fever and systemic clinical presentations, which are not attributable to the common infectious agents, should raise the suspicion of infection with above-mentioned pathogens, and appropriate laboratory tests are required. Early recognition of severe hepatitis or acute liver failure is critical in initiating appropriate and specific therapy, together with systemic supportive care, to reduce maternal and fetal mortality and long-term sequelae.     

Liver diseases in pregnancy

Mild abnormalities of liver function tests are frequently seen in pregnancy but return to normal after delivery. A raised serum alkaline phosphatase is common, along with a decline in the serum albumin, but the aminotransferases remain within normal limits. The physician must interpret abnormal liver function tests in pregnancy with these changes in mind, but most liver diseases in pregnancy result in more marked alterations. Viral hepatitis is the most common cause of jaundice in pregnancy, and the maternal prognosis is generally good. Perinatal transmission of hepatitis B virus is likely when the mother is positive for HBsAg. Concurrent administration of hepatitis B vaccine and HBIG to the infant has an efficacy of 90 per cent in preventing transmission to the infant. ICP is the second most common cause of jaundice in pregnancy. The condition is generally benign, although maternal and fetal mortality occasionally result, probably due to premature delivery and the bleeding tendency of cholestatic patients. Vitamin K administration may correct the coagulopathy, and cholestyramine is effective in controlling pruritus. AFLP is rare but carries a high mortality rate for both the mother and the fetus. Early diagnosis, correction of the coagulopathy, and prompt delivery may improve the outcome significantly. Patients with cirrhosis have reduced fertility, and in those who become pregnant, fetal loss is high. The effect of pregnancy or hepatocellular function is variable, but, when evidence of liver failure is present in the first trimester, termination should be considered. Variceal size and the risk of bleeding may be assessed by endoscopy. Pregnant cirrhotic patients with large esophageal varices and a history of bleeding can undergo shunt surgery. Conservative management may be appropriate for patients with small varices and no history of bleeding.     

Acute fatty liver of pregnancy and acetaminophen toxicity leading to liver failure and postpartum liver transplantation. A case report

BACKGROUND: Acute fatty liver of pregnancy is a rare entity. A MEDLINE English-language search from 1966 to the present revealed no reports of acetaminophen toxicity and acute fatty liver in pregnancy. CASE: An 18-year-old, African American woman, gravida 1, presented at 33 weeks' gestation with signs and symptoms consistent with acute fatty liver of pregnancy and fetal death. Markedly elevated transaminases prompted a search for other etiologies, and acetaminophen toxicity was diagnosed. Liver biopsy revealed acute fatty liver of pregnancy and toxin-induced injury consistent with acetaminophen use. The patient's condition deteriorated, resulting in fulminant hepatic failure and requiring postpartum orthotopic liver transplantation. CONCLUSION: The combination of acute fatty liver of pregnancy and acetaminophen toxicity resulted in acute liver failure. Attention to clinical and biochemical parameters can lead to diagnosis and management.     

Reversible peripartum liver failure: a new perspective on the diagnosis, treatment, and cause of acute fatty liver of pregnancy, based on 28 consecutive cases.

OBJECTIVE: We sought to describe our experience with the clinical diagnosis, management, and course of patients with acute fatty liver of pregnancy. STUDY DESIGN: Twenty-eight cases of acute fatty liver of pregnancy at the Los Angeles County and University of Southern California Medical Center from 1982 to June 1997 were identified, and presenting symptoms, clinical course, laboratory values, maternal complications, and neonatal outcomes were studied. RESULTS: The incidence of acute fatty liver of pregnancy was 1 in 6659 births. There were no maternal deaths. Initial presentation was at an average of 37 weeks of gestation with a characteristic prodrome of malaise, nausea, vomiting, and abdominal pain. No patient was admitted with the diagnosis of acute fatty liver of pregnancy. The condition was diagnosed most commonly on the second hospital day after laboratory results indicated coagulopathy, renal insufficiency, and liver function abnormalities. One patient underwent liver biopsy at cesarean delivery. Radiologic studies did not aid with the diagnosis. Twenty-one patients were admitted in spontaneous labor, and 16 labors were complicated by abnormal fetal heart rate patterns or meconium. There was 1 stillbirth and 1 neonatal death as a result of perinatal asphyxia. Maternal morbidity consisted of hypoglycemia, infection, renal insufficiency, coagulopathy, encephalopathy, and wound complications. All patients had evidence of disseminated intravascular coagulopathy with profoundly decreased antithrombin levels. All patients recovered normal liver function post partum. CONCLUSIONS: Reversible peripartum liver failure may be diagnosed and managed on the basis of clinical and laboratory criteria. With adequate support, these patients may have full recovery of hepatic function.     

Diagnóstico posparto de la enfermedad de Wilson en gestante con síndrome HELLP y coagulopatía

HELLP syndrome is a clinical-analytical entity defined by microangiopathic hemolytic anemia, elevated liver enzymes, and thrombocytopenia. Liver involvement in this syndrome is common to several liver diseases. Some of these liver diseases are inherent to pregnancy (acute fatty liver of pregnancy, gestational intrahepatic cholestasis), while others are related to intercurrent disease (acute viral hepatitis) or to previous chronic liver disease. We report a case of postpartum diagnosis of chronic liver disease secondary to Wilson disease, with onset in the third trimester of pregnancy and HELLP syndrome associated with acute liver failure and coagulopathy. We review the differential diagnosis and the scientific literature on the topic.     

Diagnosis of early acute fatty liver of pregnancy

Acute fatty liver of pregnancy (AFLP) is usually diagnosed at autopsy, with severe hepatic failure, or after the appearance of extrahepatic disease. We present an atypical patient with mild AFLP in whom hepatic biopsy allowed earlier diagnosis. A low threshold for liver biopsy in patients not experiencing fulminant disease can afford diagnostic information prior to the onset of serious sequelae.     

Fatal disseminated herpes simplex virus infection in a previously healthy pregnant woman. A case report

BACKGROUND: In contrast to the frequent occurrence of localized herpes simplex virus (HSV) infections during pregnancy, disseminated disease has rarely been reported. CASE: A 21-year-old woman in the 27th week of gestation developed a catastrophic illness characterized by fever, progressive pneumonia, respiratory failure, leukopenia, disseminated intravascular coagulation (DIC), anicteric hepatitis, septic shock and acute renal failure. Initial studies for an infectious etiology were negative. In spite of empiric broad-spectrum antimicrobial therapy, her condition continued to deteriorate. Sparse vesicular skin lesions suggestive of HSV infection subsequently appeared. Despite initiation of acyclovir therapy, the patient died. HSV type 2 was cultured from a skin vesicle, and at autopsy there was extensive necrosis of the liver and lung with immunohistochemical stains positive for HSV antigen. CONCLUSION: In the third trimester of pregnancy, HSV can occasionally disseminate in immunocompetent women. A clinical syndrome of unexplained fever, pneumonia, anicteric hepatitis, leukopenia and DIC without mucocutaneous lesions should prompt investigation and possible treatment for disseminated HSV infection.     

Liver diseases and pregnancy. II: Liver diseases without causal relation to pregnancy--general principles for treatment of patients with liver disease

In addition to a previous paper [7] a survey is given of acute viral hepatitis, drug-induced liver-disease, chronic hepatitis, cirrhosis of the liver, hyperbilirubinemia, hepatic porphyria, and obstructive jaundice as hepatobiliary diseases independent of pregnancy. Finally, some questions of treatment of pregnant women suffering from liver disease are stressed.     

Acute fatty liver in the second trimester

Background: Acute fatty liver of pregnancy is a rare, potentially fatal disease that occurs in the late third trimester or early postpartum period. The case of a woman with acute fatty liver in the second trimester is presented.Case: A 35-year-old woman, gravida 5, para 4, presented at 22 weeks’ gestation with nausea, vomiting, malaise, weight loss, and moderately elevated liver transaminase levels. The differential diagnoses included viral gastroenteritis and cholelithiasis. During the next 12 days, her transaminase levels increased, jaundice developed, her sensorium changed, and coagulopathy appeared. After the patient was transferred to a tertiary care hospital, acute fatty liver of pregnancy was diagnosed. The woman rapidly improved after delivery.Conclusion: Although acute fatty liver of pregnancy usually occurs in the late third trimester or early postpartum period, it can occur in the second trimester.     

Acute fatty liver of pregnancy: a retrospective study of 32 cases in South China

Abstract

Objective: To describe 32 cases of acute fatty liver of pregnancy (AFLP) and identify the potential clinical predictors of maternal and fetal outcomes in South China.

Methods: Thirty-two cases of AFLP previously treated in the First Affiliated Hospital of Nanchang University in the past 10 years were enrolled in the current study.

Results: Sex of fetus and delivery method was the potential clinical predictor of fetal outcome. The main manifestations of AFLP were jaundice (n?=?32), nausea and vomiting (n?=?28), malaise (n?=?25), and ascites (n?=?25), and its complications included acute renal failure (n?=?26), hepatic encephalopathy (n?=?17), infection (n?=?10), and postpartum hemorrhage (n?=?7). Evidence of fatty changes of liver was demonstrated by B ultrasound and computed tomography (CT). Eighteen patients were recovered due to rapid diagnosis, early termination of pregnancy and supportive treatments.

Conclusions: Male sex and vaginal delivery was the risk factor of fetal outcome. Detailed history taking and proper management of potential predictors are important in making the decision of prompt delivery and choosing the appropriate delivery method. Further studies are needed to expand our knowledge on this disease.     

Antenatal detection of abnormal liver function tests - a marker for poor perinatal outcome.

The purpose of this study was to examine (a) the incidence of liver disease diagnosed in our antenatal population, (b) the diagnostic value of initial symptoms and liver function tests (LFTs), (c) the adequacy of investigation and management of the liver disorder and (d) the obstetric and neonatal outcome in this group of patients. Women with abnormal LFTs that delivered at our hospital over a 2-year period were identified from computerised hospital records and data was obtained from chart review. Forty-six out of a total of 13 181 (0.35%) women had liver disease diagnosed in pregnancy: Diagnoses included intrahepatic cholestasis of pregnancy (13), pre-eclampsia and the HELLP syndrome (eight), acute fatty liver of pregnancy (three), hyperemesis gravidarum (one), hepatitis C (13), B (four) and hepatitis A (one), cholelithiasis (two) and hepatitis of unknown aetiology (one). Symptoms at presentation were more predictive of the final diagnosis than the initial LFT profile. Investigation of the liver disorder was incomplete in 50% of cases.One mother required intensive care for 6 weeks postpartum and three others had significant postpartum haemorrhage. There was one neonatal death and 24 neonates were admitted to the special care baby unit. Eighteen women attended for their postnatal check up at 6 weeks. Eight of these women were referred to a hepatologist. Detection of liver disease in pregnancy identifies a group at risk of poor neonatal and maternal outcome. Structured guidelines should be implemented in obstetric units to facilitate appropriate investigation, treatment and referral patterns for these women.     

Primary hepatic malignancy in pregnant women.

Three women dying from hepatic carcinoma during pregnancy are presented. One of these women with a hepatocellular carcinoma and alpha fetoprotein in the serum and antibody to hepatitis B antigen. A fourth patient died 2 months post partum with a cholangiocarcinoma. A false positive pregnancy test suggested that she had metastatic choriocarcinoma in the liver, and a panhysterectomy was performed. The clinical diagnosis with the use of alpha fetoprotein and chorionic gonadotropin for detection of hepatoma and the etiopathogenesis of primary hepatic malignancy in pregnancy are discussed.     

Clinical features of hemolysis, elevated liver enzymes, and low platelet count syndrome in undiagnosed Wilson disease: report of two cases

Introduction  

Wilson’s disease (WD) is an autosomal recessive disorder characterized by toxic accumulation of copper mainly in the liver and brain. The hepatic manifestation of WD is diverse and may include asymptomatic elevation of aminotransferase, chronic hepatitis, cirrhosis, or acute/fulminant hepatic failure. Characteristic of acute hepatic failure in WD is concomitance of acute intravascular hemolytic anemia that in some patients may represent a first clinical symptom of WD. The diagnosis of acute Wilsonian liver failure is difficult, as similar signs may be observed in other clinical conditions. In pregnant patients with unrecognized WD, liver failure with hemolysis may be interpreted as the low platelet count (HELLP) syndrome.     

Three cases of acute fatty liver of pregnancy: Postpartum clinical course depends on interval between onset of symptoms and termination of pregnancy

We report our experience with three cases of acute fatty liver of pregnancy. Case 1 complained of hydrodipsia 4 days before delivery. Case 2 presented with nausea, vomiting and dizziness 6 days before delivery. Case 3 developed loss of appetite and general fatigue with jaundice 10 days before delivery. They underwent termination of pregnancy after diagnosis was made. Case 3 still developed hepatic encephalopathy, and finally she required liver transplantation. We hypothesise that the interval between the onset of symptoms and termination of pregnancy is an important factor for acuity of the disorder and patient morbidity or mortality.     

Hepatitisinfektion in der Schwangerschaft und bei der Geburt

The most common cause of jaundice in pregnancy is viral hepatitis, potentially accompanied by temporary dysfunction of the liver. Whereas acute viral hepatitis in pregnancy frequently describes an asymptomatic course, thereby only rarely affecting the fetus, some of the known hepatitis viruses might cause severe morbidity in the neonatal period particularly when the infection is noted near term or sub partu. However, efforts have been made in order to reduce the number of acute neonatal infections (hepatitis B immune globulin and vaccine). Conversely, no immunoprophylaxis for hepatitis C is available yet, although the vertical transmission rate is low. Perinatal transmission of hepatitis E is unusual, but maternal disease is often severe. The clinical relevance of the commonly found hepatitis G virus remains unknown. Liver inflammation caused by other viruses, toxic agents or autoimmune hepatitis are rare conditions in pregnancy.