Acute Fatty Liver of Pregnancy and its Differentiation from Other Liver Diseases in Pregnancy.
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ABSTRACT:
SUBMITTER: Maier JT
PROVIDER: S-EPMC4554520 | biostudies-literature | 2015 Aug
REPOSITORIES: biostudies-literature
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Acute Fatty Liver of Pregnancy and its Differentiation from Other Liver Diseases in Pregnancy.
Maier J T JT Schalinski E E Häberlein C C Gottschalk U U Hellmeyer L L
Geburtshilfe und Frauenheilkunde 20150801 8
<b>Background:</b> There are a number of threatening liver diseases that occur during pregnancy. Acute fatty liver of pregnancy is a rare disease associated with high maternal and foetal mortality. <b>Case Report:</b> We report on a young gravida 1 woman who presented to our level 1 perinatal centre in the 36 + 5 week of pregnancy with an isolated elevation of transaminases together with diffuse upper abdominal complaints. After comprehensive diagnostic work-up we performed an emergency delivery ...[more]
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Project description:BackgroundAcute fatty liver of pregnancy (AFLP) is a serious disease with high mortality. Recent data suggest that postpartum application of artificial liver support therapy (ALST) in AFLP management improves disease outcome. In current study, we tend to further evaluate whether the type, the timing, and the number of postpartum ALST sessions and other clinical factors including complications and liver and renal function will influence disease outcome in ALST era.MethodsMedical records of 15 AFLP patients having postpartum ALST in our hospital from 2010 to 2016 were first retrospectively reviewed. A systematic review and statistical analysis was then conducted with our cases and those having postpartum ALST reported in PubMed, Embase, Cochrane, and ClinicalTrials.gov till the end of June 2016.ResultsNine relevant studies were identified in the public databases. A total of 104 cases were enrolled for analysis including 15 cases from our hospital and 89 cases from the identified 9 studies. Univariate analysis revealed that 2 complications, postpartum hemorrhage and multiple organ dysfunctions (MODS), were associated with the outcome of AFLP patients undergoing postpartum ALST. Binary logistic regression analysis further indicated that MODS was the only independent factor affecting disease outcome. Surprisingly, factors including pre-ALST serum levels of total bilirubin and creatinine, the type and number of postpartum ALST sessions, time interval between delivery and ALST were unrelated to disease outcome.ConclusionCurrent data suggest that postpartum ALST improves the outcome of AFLP patients but more properly designed experiments are needed to confirm this point. Our study further indicates that occurrence of MODS carries a bad prognosis even in ALST era. Our study provides valuable information on guiding the clinical application of postpartum ALST in AFLP management.
| S-EPMC6160087 | biostudies-literature
Project description:BackgroundLimited data exists regarding the pregnancy and infant outcomes of Acute Fatty Liver of Pregnancy (AFLP).MethodsRetrospectively collected mothers with AFLP and mothers without AFLP in our center from 1/2008 to 6/2018. The primary assessment was to analyze and compare the frequency of negative maternal and fetal outcomes. The secondary assessment was to investigate the role of intrauterine balloon tamponade in reducing negative maternal outcomes.ResultsCompared to 220 matched mothers, 55 AFLP mothers were younger (P < 0.001), with fewer pregnancies (P = 0.033), complicated with more pregnancy induced hypertension (P < 0.001), twins(P = 0.002), fetal growth restriction (P = 0.044) and male fetus (P < 0.001). 3 (5.5%) of AFLP patients were diagnosed in the postpartum period. Mean gestational week of AFLP diagnosis was 35.25 ± 5.80 weeks. Jaundice (89.1%), nausea or vomiting (58.2%), anorexia (49.1%), fatigue (45.5%) and polydipsia (30.9%) were the main prodromal symptoms. The median duration from diagnosis to delivery was 1.55 ± 4.62 days and 75% (39/52) pregnancy were terminated the pregnancy at the day of diagnosis. 78.8% (41/52) patients received cesarean section, 53.6% (22/41) of which received preventive plasma transfusion before surgery and no one received artificial liver support during the treatment. In comparison, higher frequency of 16 maternal complications, severe negative outcomes (27.3% vs. 0.9%) and newborn asphyxia (24.6% vs.0.9%) were observed in AFLP population. 3 mothers (mortality rates: 5.5%) died of multiple organ system failure and 6 fetus/infants (death rates: 9.8%) died of distress. When compared to those without negative outcomes, patients with negative fetal outcomes were younger (P = 0.042), had more singleton rates (p = 0.041), increased mean value of ALT(P = 0.011) and T-Bilirubin (P = 0.014), decreased prothrombin activity (P = 0.011). Although no statistical significance for the small sample size, there were less refractory postpartum hemorrhage (0% vs.31.3%), hysterectomy (0% vs.12.5%), negative maternal outcomes (16.7% vs.56.3%) in patients underwent intrauterine balloon tamponade when postpartum hemorrhage exceeded 500 ml.ConclusionsSeveral symptoms were found to be the main prodromal symptoms of AFLP. Higher frequency of adverse maternal and fetal outcomes was observed in mothers with AFLP than mothers without AFLP. We found five potential risk factors of negative fetal outcomes.
| S-EPMC7216501 | biostudies-literature
Project description:BackgroundAcute fatty liver of pregnancy (AFLP) is a potentially lethal condition of pregnant women with a high mortality rate. Potential predictors related to postpartum recovery time and prognostic factors of AFLP are still unclear. This study aimed to evaluate potential predictors for prognosis and postpartum recovery time of AFLP.MethodsWe retrospectively analyzed the clinical data of 76 AFLP patients in our hospital from 2002 to 2017 and investigated potential predictors using univariate analysis and multivariate logistic regression analysis.ResultsHepatic encephalopathy (HE) was found to be associated with prognosis in AFLP patients (P = 0.005, OR = 26.844). The postpartum recovery time analysis showed that AFLP patients with a age < 25 had the shortest recovery time, but no significant difference (P = 0.134, OR = 5.952). The postpartum recovery time of patients with liver failure (LF) was significantly prolonged compared to those without LF (P = 0.036, OR = 10.052). Cryoprecipitate, and plasma infusion showed no significant effect on prognosis or recovery time. Artificial liver support therapy (ALST) had no effect on prognosis, but it might affect postpartum recovery time with no statistical significance (P = 0.128, OR = 5.470).ConclusionHE is a potential predictor for prognosis of AFLP. LF is a potential predictor for postpartum recovery time.
| S-EPMC7542749 | biostudies-literature
Project description:BackgroundLiver disease is a common feature of malaria in pregnancy, but its pathogenesis remains unclear.MethodsTo understand the pathogenesis of liver disease during malaria in pregnancy, comparative proteomic analysis of the liver in a mouse model of malaria in pregnancy was performed.ResultsDecreased levels of mitochondrial and peroxisomal proteins were observed in the livers of pregnant mice infected with the lethal rodent malaria parasite Plasmodium berghei strain NK65. By contrast, increased levels of perilipin-2, amyloid A-1, and interferon (IFN)-γ signalling pathway-related proteins were observed in the livers of infected pregnant mice, suggesting that IFN-γ signalling may contribute to the development of liver disease during malaria in pregnancy. IFN-γ signalling is a potential trigger of inducible nitric oxide synthase (iNOS) expression. Liver disease associated with microvesicular fatty infiltration and elevated liver enzymes in pregnant wild-type mice infected with malaria parasites was improved by iNOS deficiency.ConclusionsIn this study, a causative role of iNOS in liver disease associated with microvesicular fatty infiltration during malaria in pregnancy was demonstrated. These findings provide important insight for understanding the role of iNOS-mediated metabolic responses and the pathogenesis of high-risk liver diseases in pregnancy, such as acute fatty liver.
| S-EPMC8670279 | biostudies-literature
Project description:Acute fatty liver of pregnancy (AFLP) is a rare but potentially life-threatening hepatic disorder that leads to considerable maternal and fetal mortality. To explore the risk factors for maternal and fetal mortality in AFLP and develop new predictive models, through this retrospective study, we analyzed the demographic characteristics, clinical symptoms, and laboratory findings of 106 patients with AFLP who were admitted to Shandong Provincial Hospital. Risk factors for maternal and fetal mortality were analyzed by univariate and multivariate logistic regression analysis. The new models based on the multivariate logistic regression analysis and the model for end-stage liver disease (MELD) were tested in AFLP. The receiver operating characteristic curve (ROC) was applied to compare the predictive efficiency, sensitivity, and specificity of the two models. Prenatal nausea (p = 0.037), prolonged prothrombin time (p = 0.003), and elevated serum creatinine (p = 0.003) were independent risk factors for maternal mortality. The ROC curve showed that the area under the curve (AUC) of the MELD was 0.948, with a sensitivity of 100% and a specificity of 83.3%. The AUC of the new model for maternal mortality was 0.926, with a sensitivity of 90% and a specificity of 94.8%. Hepatic encephalopathy (p = 0.016) and thrombocytopenia (p = 0.001) were independent risk factors for fetal mortality. Using the ROC curve, the AUC of the MELD was 0.694, yielding a sensitivity of 68.8% and a specificity of 64.4%. The AUC of the new model for fetal mortality was 0.893, yielding a sensitivity of 100% and a specificity of 73.3%. Both the new predictive model for maternal mortality and the MELD showed good predictive efficacy for maternal mortality in patients with AFLP (AUC = 0.926 and 0.948, respectively), and the new predictive model for fetal mortality was superior to the MELD in predicting fetal mortality (AUC = 0.893 and 0.694, respectively). The two new predictive models were more readily available, less expensive, and easier to implement clinically, especially in low-income countries.
| S-EPMC8374939 | biostudies-literature
Project description:Fatty liver diseases, which are commonly associated with high-fat/calorie diet, heavy alcohol consumption and/or other metabolic disorder causes, lead to serious medical concerns worldwide in recent years. It has been demonstrated that metabolic homeostasis disruption is most likely to be responsible for this global epidemic. Sirtuins are a group of conserved nicotinamide adenine dinucleotide (NAD+) dependent histone and/or protein deacetylases belonging to the silent information regulator 2 (Sir2) family. Among seven mammalian sirtuins, sirtuin 1 (SIRT 1) is the most extensively studied one and is involved in both alcoholic and nonalcoholic fatty liver diseases. SIRT1 plays beneficial roles in regulating hepatic lipid metabolism, controlling hepatic oxidative stress and mediating hepatic inflammation through deacetylating some transcriptional regulators against the progression of fatty liver diseases. Here we summarize the latest advances of the biological roles of SIRT1 in regulating lipid metabolism, oxidative stress and inflammation in the liver, and discuss the potential of SIRT1 as a therapeutic target for treating alcoholic and nonalcoholic fatty liver diseases.
| S-EPMC5555103 | biostudies-literature
Project description:BackgroundAcute fatty liver of pregnancy (AFLP) is an acute, rare and potentially lethal disease typically occurring in the third trimester of pregnancy. So far, there is no effective means of prevention. Therefore, in this study, we retrospectively analyzed the clinical features of AFLP patients for a better understanding. Meanwhile, for the first time, the genetic background associated with the onset of AFLP was discussed by high-throughput sequencing, hoping to provide evidence for genetic counseling and prenatal diagnosis of AFLP.MethodsThirteen AFLP patients admitted to our hospital and other hospital from March 2012 to February 2020 were selected. Clinical data about general condition, laboratory test, liver biopsy and the prognosis of mother and fetus were collected for retrospective analysis. In addition, the peripheral blood of five patients with AFLP and one newborn infant of his mother with AFLP was sequenced with whole-exome sequencing and gene mutation was analyzed by bioinformatics methods.ResultsThe initial symptoms of AFLP varied differently, with jaundice (9/13, 69%), fatigue (8/13, 62%) and nausea and vomiting (6/13, 46%) being the most common. Moreover, the main maternal complications were coagulopathy (13/13, 100%), followed by acute renal dysfunction (10/13, 77%). Raised serum bilirubin, transaminases and uric acid were found in all patients (100%), hypoglycemia was found in six patients (46%) and fatty liver on ultrasound was seen in five patients (5/12, 42%). One (7%) maternal death occurred and all neonates survived delivery. In addition, to our surprise, whole-exome sequencing showed that no gene mutation in related enzymes involved in fatty acid metabolism was noted in the pregnant women and children receiving genetic testing.ConclusionsEarly visit, early detection, early termination of pregnancy and multidisciplinary comprehensive treatment are the key factors to improve the prognosis of AFLP patients and their newborn infants. Furthermore, although limited size of study, to our knowledge, this report is the first to present the lack of common mutation involved in fatty acid oxidation in Chinese patients with AFLP via whole-exome sequencing. Thus, further studies are needed with larger and more varied samples to validate the conclusion.
| S-EPMC8428114 | biostudies-literature
Project description:Introduction Acute fatty liver of pregnancy (AFLP) is a rare but potentially fatal condition occurring in the third trimester or early postpartum period. It is characterized by microvesicular fatty infiltration of the liver. Clinically, the three most prominent derangements in women with AFLP are hepatic dysfunction, renal insufficiency, and impaired coagulation. AFLP is associated with an increased incidence of morbidity and mortality in neonates, though the exact cause for this remains unclear. Deficiency of vitamin K in patients with liver disease has been widely reported. Case Description We present a unique case of severe intracranial bleeding because of the early vitamin K deficiency in a neonate whose mother had AFLP along with accompanying renal insufficiency. Conclusion We suggest that monitoring infants born to mothers with AFLP, for vitamin K deficiency bleeding will help reduce morbidity and mortality in these infants.
| S-EPMC4603847 | biostudies-other
Project description:Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are the two major types of chronic liver disease worldwide. Inflammatory processes play key roles in the pathogeneses of fatty liver diseases, and continuous inflammation promotes the progression of alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH). Although both ALD and NAFLD are closely related to inflammation, their respective developmental mechanisms differ to some extent. Here, we review the roles of multiple immunological mechanisms and therapeutic targets related to the inflammation associated with fatty liver diseases and the differences in the progression of ASH and NASH. Multiple cell types in the liver, including macrophages, neutrophils, other immune cell types and hepatocytes, are involved in fatty liver disease inflammation. In addition, microRNAs (miRNAs), extracellular vesicles (EVs), and complement also contribute to the inflammatory process, as does intertissue crosstalk between the liver and the intestine, adipose tissue, and the nervous system. We point out that inflammation also plays important roles in promoting liver repair and controlling bacterial infections. Understanding the complex regulatory process of disrupted homeostasis during the development of fatty liver diseases may lead to the development of improved targeted therapeutic intervention strategies.
| S-EPMC7852578 | biostudies-literature
Project description:Nuclear receptors (NRs) play a crucial role in non-alcoholic fatty liver disease (NAFLD) and have been widely studied(Tran et al. 2018). However, the underlying mechanisms of NR regulation remain largely unclear. Here, we show that miR-20b plays a key role in modulating PPARα, a master regulator of nutrient metabolism and energy homeostasis in the pathogenesis of fatty liver(Wahli et al. 1995; Dongiovanni and Valenti 2013). Using network analysis and RNA-seq to determine the correlation between NRs and microRNA in NAFLD patients, we revealed that miR-20b directly targets PPARα. The expression of miR-20b was remarkably upregulated in free fatty acid (FA)-treated hepatocytes and the livers of both obesity-induced mice and NAFLD patients. Overexpression of miR-20b dramatically increased hepatic lipid accumulation and plasma triglyceride levels. Furthermore, miR-20b significantly reduced fatty acid oxidation and mitochondrial biogenesis by directly targeting PPARα. Fenofibrate, a specific agonist of PPARα, lost its ability to ameliorate hepatic steatosis in miR-20b-introduced mice. Finally, inhibition of miR-20b dramatically increased FA oxidation and uptake, resulting in improved insulin sensitivity and a decrease in NAFLD progression. Taken together, these results demonstrate that the novel miR-20b directly targets PPARα, plays a significant role in hepatic lipid metabolism, and presents an opportunity for the development of novel therapeutics for NAFLD.
2021-03-09 | GSE168484 | GEO