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Abnormal liver tests occur in 3%-5% of pregnancies, with many potential causes, including coincidental liver disease (most commonly viral hepatitis or gallstones) and underlying chronic liver disease. However, most liver dysfunction in pregnancy is pregnancy-related and caused by 1 of the 5 liver diseases unique to the pregnant state: these fall into 2 main categories depending on their association with or without preeclampsia. The preeclampsia-associated liver diseases are preeclampsia itself, the hemolysis (H), elevated liver tests (EL), and low platelet count (LP) (HELLP) syndrome, and acute fatty liver of pregnancy. Hyperemesis gravidarum and intrahepatic cholestasis of pregnancy have no relationship to preeclampsia. Although still enigmatic, there have been recent interesting advances in understanding of these unique pregnancy-related liver diseases. Hyperemesis gravidarum is intractable, dehydrating vomiting in the first trimester of pregnancy; 50% of patients with this condition have liver dysfunction. Intrahepatic cholestasis of pregnancy is pruritus and elevated bile acids in the second half of pregnancy, accompanied by high levels of aminotransferases and mild jaundice. Maternal management is symptomatic with ursodeoxycholic acid; for the fetus, however, this is a high-risk pregnancy requiring close fetal monitoring and early delivery. Severe preeclampsia itself is the commonest cause of hepatic tenderness and liver dysfunction in pregnancy, and 2%-12% of cases are further complicated by hemolysis (H), elevated liver tests (EL), and low platelet count (LP)-the HELLP syndrome. Immediate delivery is the only definitive therapy, but many maternal complications can occur, including abruptio placentae, renal failure, subcapsular hematomas, and hepatic rupture. Acute fatty liver of pregnancy is a sudden catastrophic illness occurring almost exclusively in the third trimester; microvesicular fatty infiltration of hepatocytes causes acute liver failure with coagulopathy and encephalopathy. Early diagnosis and immediate delivery are essential for maternal and fetal survival.
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PMID:Liver disease in pregnancy. 1826 10

Gastrointestinal complications of diabetes include gastroparesis, intestinal enteropathy (which can cause diarrhea, constipation, and fecal incontinence), and nonalcoholic fatty liver disease. Patients with gastroparesis may present with early satiety, nausea, vomiting, bloating, postprandial fullness, or upper abdominal pain. The diagnosis of diabetic gastroparesis is made when other causes are excluded and postprandial gastric stasis is confirmed by gastric emptying scintigraphy. Whenever possible, patients should discontinue medications that exacerbate gastric dysmotility; control blood glucose levels; increase the liquid content of their diet; eat smaller meals more often; discontinue the use of tobacco products; and reduce the intake of insoluble dietary fiber, foods high in fat, and alcohol. Prokinetic agents (e.g., metoclopramide, erythromycin) may be helpful in controlling symptoms of gastroparesis. Treatment of diabetes-related constipation and diarrhea is aimed at supportive measures and symptom control. Nonalcoholic fatty liver disease is common in persons who are obese and who have diabetes. In persons with diabetes who have elevated hepatic transaminase levels, it is important to search for other causes of liver disease, including hepatitis and hemochromatosis. Gradual weight loss, control of blood glucose levels, and use of medications (e.g., pioglitazone, metformin) may normalize hepatic transaminase levels, but the clinical benefit of aggressively treating nonalcoholic fatty liver disease is unknown. Controlling blood glucose levels is important for managing most gastrointestinal complications.
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PMID:Gastrointestinal complications of diabetes. 1861 80

Abnormal liver function tests occur in 3 - 5% of pregnancies for different reasons. Apart from pre-existing liver diseases liver diseases occurring during pregnancy, such as gall stones or viral hepatitis, most liver dysfunctions in pregnancy are caused by one of the five pregnancy-related liver diseases. The five known pregnancy-related liver diseases can be classified in two main categories depending on their association with or without preeclampsia. The preeclampsia-associated liver diseases are the preeclampsia itself, the HELLP-syndrome ("Hemolysis" (H), "Elevated Liver Tests" (EL), "Low Platelet Count" (LP)) and the acute fatty liver of pregnancy. Hyperemesis gravidarum and intrahepatic cholestasis of pregnancy are not associated with preeclampsia. Hyperemesis gravidarum is characterised by intractable vomiting in the first trimester of pregnancy. 50% of patients with this condition have liver dysfunction. Intrahepatic cholestasis of pregnancy presents with pruritus and elevated bile acids in the second half of pregnancy. Patients have often mild jaundice and highly elevated liver enzymes. Treatment of choice is ursodeoxycholic acid to relieve the mother's symptoms. With this condition mainly the fetus is at risk. Severe preeclampsia is the most common cause of liver dysfunction in pregnancy, and is in some cases further complicated by HELLP syndrome. The prompt delivery of the baby is the only definitive therapy. However, many life-threatening maternal complications like liver hematoma or rupture and abruptio placentae can occur. Acute fatty liver of pregnancy is also a severe illness occuring mostly in the third trimester; microvesicular fat deposition in the liver can cause liver failure with coagulopathy and encephalopathy. Only the immediate delivery of the fetus can save mother and child.
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PMID:[Liver diseases in pregnancy]. 1894 56

A 24-year-old female at 34-week gestation, presented with malaise, nausea, vomiting, jaundice, and absent foetal movements. A clinical diagnosis of acute fatty liver of pregnancy was made. Although early caesarean section was performed, postoperative course was complicated by acute respiratory distress syndrome (ARDS) sepsis, and continuing coagulopathy. Supportive management in an intensive care unit resulted in successful outcome.
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PMID:Acute fatty liver of pregnancy: a case report of an uncommon disease. 1988 Nov 79

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.
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PMID:Three cases of acute fatty liver of pregnancy: postpartum clinical course depends on interval between onset of symptoms and termination of pregnancy. 2071 81

Familial hypocholesterolemia, namely abetalipoproteinemia, hypobetalipoproteinemia and chylomicron retention disease (CRD), are rare genetic diseases that cause malnutrition, failure to thrive, growth failure and vitamin E deficiency, as well as other complications. Recently, the gene implicated in CRD was identified. The diagnosis is often delayed because symptoms are nonspecific. Treatment and follow-up remain poorly defined.The aim of this paper is to provide guidelines for the diagnosis, treatment and follow-up of children with CRD based on a literature overview and two pediatric centers 'experience.The diagnosis is based on a history of chronic diarrhea with fat malabsorption and abnormal lipid profile. Upper endoscopy and histology reveal fat-laden enterocytes whereas vitamin E deficiency is invariably present. Creatine kinase (CK) is usually elevated and hepatic steatosis is common. Genotyping identifies the Sar1b gene mutation.Treatment should be aimed at preventing potential complications. Vomiting, diarrhea and abdominal distension improve on a low-long chain fat diet. Failure to thrive is one of the most common initial clinical findings. Neurological and ophthalmologic complications in CRD are less severe than in other types of familial hypocholesterolemia. However, the vitamin E deficiency status plays a pivotal role in preventing neurological complications. Essential fatty acid (EFA) deficiency is especially severe early in life. Recently, increased CK levels and cardiomyopathy have been described in addition to muscular manifestations. Poor mineralization and delayed bone maturation do occur. A moderate degree of macrovesicular steatosis is common, but no cases of steatohepatitis cirrhosis. Besides a low-long chain fat diet made up uniquely of polyunsaturated fatty acids, treatment includes fat-soluble vitamin supplements and large amounts of vitamin E. Despite fat malabsorption and the absence of postprandial chylomicrons, the oral route can prevent neurological complications even though serum levels of vitamin E remain chronically low. Dietary counseling is needed not only to monitor fat intake and improve symptoms, but also to maintain sufficient caloric and EFA intake. Despite a better understanding of the pathogenesis of CRD, the diagnosis and management of the disease remain a challenge for clinicians. The clinical guidelines proposed will helpfully lead to an earlier diagnosis and the prevention of complications.
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PMID:Guidelines for the diagnosis and management of chylomicron retention disease based on a review of the literature and the experience of two centers. 2092 Feb 15

Liver disorders occurring during pregnancy may be specifically pregnancy-related, or may be due to an intercurrent or chronic liver disease, which may present in anyone, pregnant or not. This review focuses on the liver diseases unique to pregnancy. Hyperemesis gravidarum, which occurs during early pregnancy, may be associated with liver dysfunction. Intrahepatic cholestasis of pregnancy typically occurs during the second or third trimester. Pruritus and the associated biological signs of cholestasis improve rapidly after delivery. Mutations in gene encoding biliary transporters, especially ABCB4 encoding the multidrug resistance 3 protein, have been found to be associated with this complex disease. Ursodeoxycholic acid is currently the most effective medical treatment in improving pruritus and liver tests. Pre-eclampsia, which presents in late pregnancy frequently involves the liver, and HELLP syndrome (Hemolysis-Elevated Liver enzymes-Low Platelets) is a life-threatening complication. Prognosis of acute fatty liver of pregnancy has been radically transformed by early delivery, and clinicians must have a high index of suspicion for this condition when a woman presents nausea or vomiting, epigastric pain, jaundice, or polyuria-polydipsia during the third trimester. Acute fatty liver of pregnancy has been found to be associated with a defect of long-chain 3-hydroxyacyl coenzyme A dehydrogenase in the fetus, and mothers and their offspring should undergo DNA testing at least for the main associated genetic mutation (c.1528G>C).
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PMID:Liver diseases unique to pregnancy: a 2010 update. 2131 Jun 83

Preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low-platelet count), and acute fatty liver of pregnancy are the main causes of thrombotic microangiopathy and evere liver dysfunction during pregnancy and represent different manifestations of the same pathological continuum. The case of a 35-week pregnant woman who was admitted to an intensive care unit immediately after a Cesarean section due to fetal death and the presence of nausea, vomiting, and jaundice is reported. Postpartum preeclampsia and acute fatty liver of pregnancy were diagnosed. The patient developed an acute subdural hematoma and an intracerebral hemorrhage, which were subjected to neurosurgical treatment. The patient died from refractory hemolytic anemia and spontaneous bleeding of multiple organs. Preeclampsia HELLP syndrome, and acute fatty liver of pregnancy might overlap and be associated with potentially fatal complications, including intracranial hemorrhage, as in the present case. Early detection and diagnosis are crucial to ensure management and treatment success.
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PMID:Spontaneous acute subdural hematoma and intracerebral hemorrhage in a patient with thrombotic microangiopathy during pregnancy. 2391 84

Objectives. Our aim is to explore the clinical outcome of patients with acute fatty liver of pregnancy (AFLP), and evaluate the effect of early diagnosis and treatment. Methods. Seven patients who were diagnosed with AFLP were retrospectively analyzed from February 2005 to January 2013. The clinical records of the patients with AFLP were reviewed for clinical features, laboratory examinations, and maternal and perinatal prognosis. Routine laboratory evaluation revealed hyperbilirubinemia, moderately elevated liver transaminase, but negative serum hepatitis virus in each patient. For additional evidence, 126 cases of AFLP were reviewed retrospectively from original articles researched in A Medline-based English and Chinese Knowledge Infrastructure between the same periods. Results. The initial symptoms of all the 7 cases with AFLP were gastrointestinal symptoms; anorexia, nausea, vomiting, and progressive jaundice. Complications revealed with renal insufficiency in all 7 patients. Hepatic failure, MODS, hypoglycemia and DIC were seen in 4 patients (57.1%). Hemorrhagic shock, ARDS, and hepatic encephalopathy were seen in 3 patients (42.8%). There was only one case of maternal death (14.2%), three cases of perinatal death (30%) and one postnatal death (10%). Conclusion. AFLP occurs in late pregnancy is a rare clinical syndrome occurs at about 36 weeks of gestation. Early diagnosis and prompt termination of pregnancy is the key of management with multidisciplinary collaboration, comprehensive treatment and effective prevention are helpful to improve prognosis of the cases with AFLP and perinatal death.
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PMID:Retrospective study of seven cases with acute Fatty liver of pregnancy. 2393 63

Multiple Acyl-CoA dehydrogenation deficiency (MADD) is an autosomal recessive disorder of fatty acid oxidation and amino-acid metabolism. Most patients with late-onset MADD are well responsive to treatment with riboflavin, which is also termed as riboflavin-responsive MADD (RR-MADD). In this study, we summarized the clinical profiles and genetic features of 13 Chinese patients with RR-MADD and reanalyzed the existing data on RR-MADD patients in Mainland China. In a cohort comprising 13 patients, all were seen to present with severe muscular symptoms occasionally accompanied with mild involvements of extramuscular organs. A total of 18 mutations (13 reported and 5 novel) of the ETFDH gene were identified in this series of patients. Exon deletion/duplication was not found in all patients. ETF:QO expression from the muscle specimens was significantly decreased in all patients. At the time of this study the total number of RR-MADD cases had reached 148 in Mainland China since 2009. The muscle symptoms in Mainland China were similar to those in other regions. However, the common extramuscular symptoms were fatty liver and recurrent vomiting in mainland Chinese patients rather than encephalopathy found in Caucasian patients. A total of 68 mutations had been identified in 148 patients with RR-MADD. The c.250G>A had a high mutation frequency in Southern China, whereas c.770A>G and c.1227A>C were more geographically widespread hot spot mutations in Mainland China.
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PMID:Riboflavin-responsive multiple Acyl-CoA dehydrogenation deficiency in 13 cases, and a literature review in mainland Chinese patients. 2452 93


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