Search Results (12)

Acute liver injury during pregnancy is rare and predominantly associated with pregnancy-related conditions including acute fatty liver of pregnancy; Hemolysis, Elevated Liver Enzymes and Low Platelets syndrome; intrahepatic cholestasis of pregnancy; and preeclampsia. Drug-induced liver injury (DILI) is a less common and often overlooked cause of acute liver injury in pregnant patients. A literature search on acute liver injury during pregnancy and therapeutic plasma exchange was conducted, revealing the most common causative factors and syndromes. A 39-year-old woman was diagnosed with acute liver injury in the 23rd week of her third pregnancy and, upon extensive differential diagnoses, a suspicion of DILI occurred after the use of methyldopa. Methyldopa, the drug of choice for the treatment of hypertensive disorders of pregnancy, has a high safety profile for the developing fetus and is well tolerated by pregnant women, yet, in susceptible individuals, a hepatotoxic effect may occur. The drug was discontinued and symptomatic treatment with ursodeoxycholic acid and prednisone was implemented with marginal effect. Upon a multidisciplinary joint consultation, plasmapheresis procedures were introduced, granting a significant improvement in the patient’s liver function and enabling the continuation of the pregnancy. Plasmapheresis treatment was safely and effectively used for the first time in the therapeutic process in a pregnant patient with DILI. Interdisciplinary cooperation of specialists with gastroenterology, nephrology, and obstetrics expertise is crucial to achieving a timely diagnosis and begin effective treatment for pregnant patients with acute liver injury. Full article

During pregnancy, a series of physiological changes occur in women, particularly affecting the cardiovascular system with significant hemodynamic alterations. Subsequently, this leads to renal adaptations manifesting through variations in glomerular filtration rate. This close interconnection between the heart and kidneys implies that issues arising in one organ will disrupt this fundamental balance, inevitably involving all associated organs. The purpose of this review is to gather all possible nephrological conditions that may arise during pregnancy, as well as pre-existing conditions that may become apparent or worsen during this period. This review describes the natural history, treatment, and impact of these conditions on pregnancy itself. Among the most common conditions are preeclampsia and HELLP syndrome, severe complications characterized by hypertension, proteinuria, and multiorgan damage that require immediate clinical attention. Additionally, women with chronic kidney disease are at higher risk of developing maternal–fetal complications, such as preterm birth and intrauterine growth restriction. Common causes of acute renal failure are also analyzed, including thrombotic microangiopathy, acute fatty liver of pregnancy, acute onset or flare of systemic lupus erythematosus, and catastrophic antiphospholipid antibody syndrome. Given the importance of proper renal function during pregnancy, it is essential to have a thorough understanding of nephrological diseases that may affect this phase of women’s lives. This knowledge is crucial for managing these conditions effectively to avoid risks to the survival of both the mother and the newborn. Full article

Mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies have been a part of the Slovenian newborn screening (NBS) program since 2018. We describe a case of early lethal presentation of MTPD/LCHADD in a term newborn. The girl was born after an uneventful pregnancy and delivery, and she was discharged home at the age of 3 days, appearing well. At the age of 4 days, she was found without signs of life. Resuscitation was not successful. The NBS test performed using tandem mass spectrometry (MS/MS) showed a positive screen for MTPD/LCHADD. Genetic analysis performed on a dried blood spot (DBS) sample identified two heterozygous variants in the HADHA gene: a nucleotide duplication introducing a premature termination codon (p.Arg205Ter) and a nucleotide substitution (p.Glu510Gln). Post-mortem studies showed massive macro-vesicular fat accumulation in the liver and, to a smaller extent, in the heart, consistent with MTPD/LCHADD. A neonatal acute cardiac presentation resulting in demise was suspected. We conducted a systematic literature review of early neonatal deaths within 14 days postpartum attributed to confirmed fatty acid oxidation disorders (FAODs), which are estimated to account for 5% of sudden infant deaths. We discuss the pitfalls of the NBS for MTPD/LCHADD. Full article

Acute fatty liver of pregnancy (AFLP), although rare, is a potentially fatal obstetrical disorder. It is characterized by acute liver failure of varying degrees with associated coagulopathy that occurs often in the third trimester of pregnancy. The following review discusses the history, etiopathogenesis, and subsequent clinical and laboratory findings that are associated with this disorder. It additionally attempts to aid in differentiating AFLP from other common obstetrical and non-obstetrical diseases with special emphasis on its differentiation from hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. This review also discusses recommendations for delivery and postpartum care with focus on return to baseline and additional life-saving measures that may need to be pursued in the most difficult and refractory cases. Finally, it addresses maternal and perinatal outcomes associated with the disorder and the effect that this disorder can have on future pregnancies. Full article

Liver disease is not uncommon during pregnancy and is associated with increased maternal and fetal/neonatal morbidity and mortality. Physiological changes during pregnancy, including a hyperestrogenic state, increase in circulating plasma volume and/or reduction in splanchnic vascular resistance, and hemostatic imbalance, may mimic or worsen liver disease. For the clinician, it is important to distinguish among the first presentation or exacerbation of chronic liver disease, acute liver disease non-specific to pregnancy, and pregnancy-specific liver disease. This last group classically includes conditions such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, liver disorders associated with the pre-eclampsia spectrum, and an acute fatty liver of pregnancy. All of these disorders often share pathophysiological mechanisms, symptoms, and laboratory findings (such as elevated liver enzymes), but a prompt and correct diagnosis is fundamental to guide obstetric conduct, reduce morbidity and mortality, and inform upon the risk of recurrence or development of other chronic diseases later on in life. Finally, the cause of elevated liver enzymes during pregnancy is unclear in up to 30–40% of the cases, and yet, little is known on the causes and mechanisms underlying these alterations, or whether these findings are associated with worse maternal/fetal outcomes. In this narrative review, we aimed to summarize pragmatically the diagnostic work-up and the management of subjects with elevated liver enzymes during pregnancy. Full article

The liver is one of the richest organs in mitochondria, serving as a hub for key metabolic pathways such as β-oxidation, the tricarboxylic acid (TCA) cycle, ketogenesis, respiratory activity, and adenosine triphosphate (ATP) synthesis, all of which provide metabolic energy for the entire body. Mitochondrial dysfunction has been linked to subcellular organelle dysfunction in liver diseases, particularly fatty liver disease. Acute fatty liver of pregnancy (AFLP) is a life-threatening liver disorder unique to pregnancy, which can result in serious maternal and fetal complications, including death. Pregnant mothers with this disease require early detection, prompt delivery, and supportive maternal care. AFLP was considered a mysterious illness and though its pathogenesis has not been fully elucidated, molecular research over the past two decades has linked AFLP to mitochondrial dysfunction and defects in fetal fatty-acid oxidation (FAO). Due to deficient placental and fetal FAO, harmful 3-hydroxy fatty acid metabolites accumulate in the maternal circulation, causing oxidative stress and microvesicular fatty infiltration of the liver, resulting in AFLP. In this review, we provide an overview of AFLP and mitochondrial FAO followed by discussion of how altered mitochondrial function plays an important role in the pathogenesis of AFLP. Full article

Hepatic dysfunction in pregnant women is always challenging for the obstetrician, as the spectrum of hepatic abnormalities can be very large and have various implications, both for mother and fetus. There is a diagnostic and therapeutic polymorphism of hepatic dysfunction in pregnancy and insufficient knowledge related to the etiopathogenesis and epidemiology of this disease. The clinical forms of hepatic dysfunction encountered in pregnancy can vary from liver diseases related to pregnancy (e.g., HELLP syndrome, intrahepatic cholestasis, hyperemesis gravidarum, or acute fatty liver of pregnancy) to de novo ones occurring in pregnancy, and pre-existing liver disease (cholelithiasis, Budd–Chiari syndrome, and cirrhosis). We performed a systematic literature search over 10 years. The review protocol assumed a search of two databases (PubMed^®/MEDLINE and Web of Science Core Collection). The strategy regarding the management of these diseases involves multidisciplinary teams composed of different specialists (obstetricians, gastroenterologists and anesthetists) from specialized tertiary centers. Despite the improving prognosis of pregnant women with liver diseases, the risk of maternal–fetal complications remains very high. Therefore, it is necessary to ensure careful monitoring by a multidisciplinary team and to inform the patients of the potential risks. Full article

Liver disease in pregnancy may present as an acute condition related to the gestational period, characterized by pruritus, jaundice, and abnormal liver function. The disease may be misdiagnosed with other liver diseases, some of which may have consequences for fetal health. It is therefore advisable to implement rapid diagnostic strategies to provide information for the management of pregnancy in these conditions. We report the case of a healthy woman with a twin pregnancy from homologous in vitro fertilization (IVF), who in the third trimester presented jaundice and malaise. Biochemical investigations and liver hyperechogenicity raised the suspicion of acute fatty liver disease of pregnancy (AFLP). Non-invasive prenatal whole-exome sequencing (WES) in the trio identified the Phe305Ile heterozygous variant in the ATP8B1 gene. Considering the twin pregnancy, the percentage of the variant versus the wild allele was of 31%, suggesting heterozygosity present in the mother alone. This analysis showed that the mother was affected by benign recurrent intrahepatic cholestasis of pregnancy (ICP1: # 147480) and indicated the opportunity to anticipate childbirth to avoid worsening of the mother’s health. WES after the birth of the twins confirmed the molecular data. Full article

This article discusses the importance and effectiveness of viscoelastic hemostatic assays (VHAs) in assessing hemostatic competence and guiding blood component therapy (BCT) in patients with postpartum hemorrhage (PPH). In recent years, VHAs such as thromboelastography and rotational thromboelastometry have increasingly been used to guide BCT, hemostatic adjunctive therapy and prohemostatic agents in PPH. The three pillars of identifying hemostatic competence include clinical observation, common coagulation tests, and VHAs. VHAs are advantageous because they assess the cumulative contribution of all components of the blood throughout the entire formation of a clot, have fast turnaround times, and are point-of-care tests that can be followed serially. Despite these advantages, VHAs are underused due to poor understanding of correct technique and result interpretation, a paucity of widespread standardization, and a lack of large clinical trials. These VHAs can also be used in cases of uterine atony, preeclampsia, acute fatty liver of pregnancy, amniotic fluid embolism, placental abruption, genital tract trauma, surgical trauma, and inherited and prepartum acquired coagulopathies. There exists an immediate need for a point-of-care test that can equip obstetricians with rapid results on developing coagulopathic states. The use of VHAs in predicting and treating PPH, although in an incipient state, can fulfill this need. Full article

Acute fatty liver of pregnancy (AFLP), a catastrophic illness for both the mother and the unborn offspring, develops in the last trimester of pregnancy with significant maternal and perinatal mortality. AFLP is also recognized as an obstetric and medical emergency. Maternal AFLP is highly associated with a fetal homozygous mutation (1528G>C) in the gene that encodes for mitochondrial long-chain hydroxy acyl-CoA dehydrogenase (LCHAD). The mutation in LCHAD results in the accumulation of 3-hydroxy fatty acids, such as 3-hydroxy myristic acid, 3-hydroxy palmitic acid and 3-hydroxy dicarboxylic acid in the placenta, which are then shunted to the maternal circulation leading to the development of acute liver injury observed in patients with AFLP. In this review, we will discuss the mechanistic role of increased 3-hydroxy fatty acid in causing lipotoxicity to the liver and in inducing oxidative stress, mitochondrial dysfunction and hepatocyte lipoapoptosis. Further, we also review the role of 3-hydroxy fatty acids in causing placental damage, pancreatic islet β-cell glucolipotoxicity, brain damage, and retinal epithelial cells lipoapoptosis in patients with LCHAD deficiency. Full article

Objectives. Acute liver failure (ALF) is a life-threatening condition that can rapidly progress into coma and death due to the cerebral edema and multi-organ dysfunction. The ALF etiology and risk factors have been investigated inWest Europe, North America, and Asia; however, there are still no published data about the causes and prognosis of ALF in Central and East European countries. The aim of our study was to analyze the causes, outcomes, and prognostic factors of ALF in patients referred to tertiary care center in Lithuania.
Material and methods. A total of 28 consecutive patients admitted to the tertiary care center (one of two university-level medical centers in Lithuania) over the period of January 1996 and December 2004 and who fulfilled the entry criteria of ALF (presence of hepatic encephalopathy (HE) and prothrombin international normalized ratio (INR) >1.5) were included into a prospective study.
Results. In our study the most frequent causes of ALF were acute viral hepatitis B (21.4 %), drug-induced hepatitis (21.4%), and indeterminate hepatitis (17.9%); other etiologies included Budd-Chiari syndrome (10.7%), ischemic hepatitis (10.7%), Wilson’s disease (7.1%), Amanita phalloides-induced liver damage (3.6%), acute fatty liver of pregnancy (3.6%), and malignant infiltration of the liver (3.6%). Among patients with drug-induced liver injury, only one case of acetaminophen poisoning was diagnosed. Clinical status of 9 persons in all patients with ALF corresponded to criteria for liver transplantation (LT) (one liver transplantation was performed), 6 of them had contraindications, and 13 patients did not fulfill requirements for urgent LT. The patients’ survival rate in these groups was 11.1%, 16.7% and 69.2%, respectively. In 27 nontransplanted patients univariate analysis revealed the grade of HE on the day of enrolment, total serumbilirubin, pH, and prothrombin INR as risk factors for death fromALF.Multivariate logistic regressive analysis determined only prothrombin INR >3.24 and serum pH £7.29 as independent predictors of lethal outcome in ALF.
Conclusions. Acute viral hepatitis B, drug-induced liver injury, and indeterminate hepatitis are the main ALF causes in Lithuania. In non-transplanted patients, the main predictors of lethal outcome were severe coagulopathy and metabolic acidosis. Improvement of liver donation system for urgent liver transplantation is essential requirement for amelioration of ALF patient’s survival. Full article

The aim of this review article is to improve knowledge of the liver disease in pregnancy. The article summarizes the results of own experience and the recent reviews of liver disorders unique to pregnancy. Abnormalities in liver tests occur in 3% of pregnancies with causes ranging from self-limiting to rapidly fatal. In Kaunas University of Medicine Hospital, a retrospective analysis disclosed a rate of 0.52% of liver diseases in 16252 pregnant women over a 5-year period. Several liver diseases occur only during pregnancy and are considered to be associated with the pregnant state. The liver disorders unique to pregnancy have characteristic clinical features and timing of onset. Hyperemesis gravidarum occurs in the first trimester, intrahepatic cholestasis of pregnancy in the second or third trimester, preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome, and acute fatty liver of pregnancy usually in the third trimester. The disorders of late pregnancy – preeclampsia, HELLP syndrome, and acute fatty liver of pregnancy – may progress to severe liver dysfunction. The correct diagnosis is critical, as any delay can result in morbidity or mortality of both the mother and fetus. Early delivery and advances in supportive management are the only available option for improving the prognosis. Full article