Acute Fatty Liver Disease Research Articles

Acute fatty liver of pregnancy: An atypical case report

HIGHLIGHTS Acute Fatty Liver of Pregnancy (AFLP) is an uncommon condition but life-threatening obstetric emergency, that increases the risk of fetal death due to preterm birth. AFLP can be challenging for primary health workers (especially for general practitioners (GP) and midwives) since it mimics preeclampsia, viral hepatitis, intrahepatic cholestasis of pregnancy, and HELLPS syndrome, so more concern is needed in this case. ABSTRACT Objective: To present an atypical case of acute fatty liver of pregnancy. Case Report: A 33-year-old woman was referred to the Emergency department of Dr. Soedarso Tertiary Referral Hospital, Pontianak, Indonesia, previously from the district hospital over 580 KM with diagnosis of multigravida (gravida 3 para 2) at 31 weeks gestation, suspected acute fatty liver disease (AFLP), severe oligohydramnios, and intrauterine growth restriction (IUGR). The patient had a history of nausea, vomiting, epigastric pain, polydipsia and polyuria, and seizure for less than 5 minutes with loss of consciousness. The patient originally did not know she was pregnant and using a contraceptive implant. She missed her period in the last six months ago, which was the first onset of epigastric pain. Further clinical examination resulted in pitting oedema but jaundice as a cardinal sign was not present. Laboratory data showed leukocytosis, normal haemoglobin level, normal blood glucose, hyperuricemia, increased function liver test with high transaminase and bilirubin, normal coagulation profile. Urinalysis showed proteinuria. The viral hepatitis and HIV tests were negative. Transabdominal ultrasound demonstrated a single intrauterine pregnancy with no echogenic liver features. Cardiotocography (CTG) showed category 2. This patient was diagnosed with AFLP based on Swansea Criteria (7 out of 10) and terminated pregnancy two days after diagnosis. A baby boy was born with birth weight 1.100 gr, birth length 34 cm, apgar score (AS) 9 and 10 at 1 and 5 minutes. The mother had a good prognosis, while the baby died on day 23 of life. Conclusion: Acute Fatty Liver during Pregnancy is an uncommon but life-threatening obstetric emergency. Early screening, diagnosis, timely handling delivery, and intensive supportive care are essential to decrease morbidity and mortality for both mother and fetus. Multidisciplinary opinion needed for the best management of this case.

ZnR/GPR39 regulates hepatic insulin signaling, tunes liver bioenergetics and ROS production, and mitigates liver fibrosis and injury

Adequate supply of zinc is essential for hepatic function and its deficiency is associated with acute liver injury (ALI) and chronic nonalcoholic fatty liver disease (NAFLD). However, how zinc controls hepatic function is unknown. We found that the zinc sensitive ZnR/GPR39, a mediator of zinc signaling, enhances hepatic phosphorylation of ERK1/2, which is reduced in ZnR/GPR39 deficient livers. Surprisingly, livers from ZnR/GPR39 knockout (KO) mice exhibited elevated insulin receptor expression and downstream AKT activation. Moreover, ZnR/GPR39 KO mice had higher blood fasting glucose level, pronounced hepatic lipid accumulation, increased hepatocyte oxygen consumption rate (OCR) and reactive oxygen species (ROS) levels. These data suggest that ZnR/GPR39 modulates insulin receptor signaling, a major pathway in hepatic metabolism. Associated with the impaired signaling, ZnR/GPR39 KO livers exhibited increased tissue fibrosis, manifested by marked elevation of collagen expression, compared to wildtype (WT). Additionally, we found alteration of hepatocyte junctional proteins that was accompanied by increased macrophage infiltration and higher liver inflammation in ZnR/GPR39 KO mice. To determine the role of ZnR/GPR39 in ALI, we applied a mild LPS challenge that induced profound decrease in hepatic OCR, also leading to higher ROS generation in ZnR/GPR39 KO hepatocytes, but not in WT. We further found increased serum IL-2 and AST/ALT ratio only in ZnR/GPR39 KO mice. Our findings reveal a role of ZnR/GPR39 in controlling hepatic insulin receptor signaling and mitigating liver fibrosis and inflammation, thus underscoring the important role of ZnR/GPR39 in liver signaling and function.

Thrombotic Microangiopathy in the Postpartum Period (Literature Review, Clinical Case Report)

Introduction. Thrombotic microangiopathy (TMA) is a heterogeneous group of diseases that, in the presence of endothelial damage, can lead to microvascular thrombosis, secondary platelet consumption, mechanical hemolysis and ischemic end-organs damage. Such triad of symptoms as acute kidney injury (AKI), microangiopathic hemolysis and thrombocytopenia may also accompany some pregnancy-specific conditions (severe preeclampsia/HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count), acute fatty liver disease of pregnancy (AFLP), and conditions not related to pregnancy, but triggered by it (catastrophic antiphospholipid syndrome (CAPS), lupus flare. The aim of the study. To review the current literature devoted to the problem of thrombotic microangiopathy, to demonstrate on a clinical case a step-by-step differentiated approach to the diagnosis of the type of thrombotic microangiopathy causing acute kidney injury in the postpartum period, and to describe modern methods of treatment of these diseases. Results. The classical types of TMA are thrombotic thrombocytopenic purpura (TTP) and typical hemolytic uremic syndrome (HUS), also known as enterohemorrhagic Shiga toxin-producing Escherichia coli (STEC)-associated HUS (STEC-HUS). Pathophysiologically, all forms of TMA involve complement-mediated endothelial cell damage, which mainly affects the capillary zone of the kidney. Pregnancy can trigger atypical HUS (aHUS) or TTP. The article describes the clinical case of a 37-year-old woman who developed AKI following a complicated delivery. A turn-based differential diagnosis of aHUS was performed. Unwarranted discontinuation of the targeted therapy with Eculisumab led to the development of chronic renal failure Conclusions. Thrombotics microangiopathy are the life-threatening conditions rarely seen in pregnancy making its early recognition difficult. As thrombotics microangiopathy require urgent treatment, plasmapheresis should be started as soon as they are suspected, followed by targeted therapy (Eculisumab, Rituximab) after the confirmation of the diagnosis. This may contribute to reducing maternal morbidity and mortality rates.

Acute fatty liver disease of pregnancy.

Acute fatty liver disease of pregnancy.

The association between acute fatty liver disease and nitric oxide during malaria in pregnancy

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.

Omega‑3 polyunsaturated fatty acids inhibit IL‑11/STAT3 signaling in hepatocytes during acetaminophen hepatotoxicity.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert a negative effect on IL-6 production in several liver disorders, including cirrhosis, acute liver failure and fatty liver disease. However, its effect on the production of IL-11, another important IL-6 family cytokine, remains unclear. IL-11 was found to be significantly elevated in acetaminophen (APAP)-induced liver damage. The aim of the present study was to investigate whether and how n-3 PUFAs modulate IL-11 production during APAP-induced liver injury. For that purpose, wild-type (WT) and fat-1 transgenic mice were intraperitoneally injected with APAP to induce liver injury. Serum was collected for ELISA and alanine aminotransferase assay. The hepatocytes of APAP-injected mice were isolated for reverse transcription-quantitative PCR and western blot analyses. For the in vitro study, primary hepatocytes isolated from WT or fat-1 mice were stimulated with APAP. The results revealed that both endogenous and exogenous n-3 PUFAs significantly aggravated APAP-induced liver damage via the downregulation of STAT3 signaling. Notably, n-3 PUFAs inhibited IL-11 expression, but not IL-6 expression in hepatocytes during the APAP challenge. Furthermore, it was demonstrated that limited phosphorylation of ERK1/2 and Fos-like-1 (Fra-1) expression are responsible for the n-3 PUFA-mediated inhibitory effect on IL-11 production in APAP-treated hepatocytes. It was concluded that n-3 PUFAs inhibit IL-11 production and further STAT3 activation in hepatocytes during APAP-induced liver injury. Therefore, ERK1/2-mediated Fra-1 expression is responsible for the effect of n-3 PUFAs on IL-11 expression.

A rare presentation of acute fatty liver disease in pregnancy in the background of T-cell non-Hodgkin lymphoma

No abstract available

Pregnancy-related liver pathology: hyperemesis gravidarum, cholestatic hepatosis of pregnancy, preeclampsia/eclampsia, HELLP-syndrome, acute fatty liver of pregnancy

Liver disease associated with pregnancy affects up to 3% of women and is a common cause of dysfunction during pregnancy. Severe liver dysfunction is associated with high rates of maternal and infant morbidity and mortality.Therefore, it is important to know about liver diseases the woman suffered before pregnancy in order to adequately manage the pregnancy and reduce the number of complications during delivery. Research and recent advances in medicine tend to improve the consequences, but so far they have not shown significant reduction of the maternal and perinatal morbidity rates against the background of this pathology. Liver diseases that are characteristic for pregnancy can be classified into those of early pregnancy (hyperemesis gravidarum) and those of late pregnancy (preeclampsia/eclampsia, intrahepatic cholestasis of pregnant women; hemolysis, increased activity of liver enzymes) HELLP-syndrome, acute fatty liver disease of pregnant women - AFLP, liver rupture / infarction).The results of modern studies used in the practice of medical care for pregnant women with concomitant pathology have significantly improved the pregnancy and delivery outcomes, but the number of complications among the mother and the fetus is still high. In this article, we offer an overview of liver diseases complicated by pregnancy with a detailed presentation of their aetiology, pathogenesis, diagnosis, and treatment. The risk groups of pregnant women with the potential possibility of liver dysfunction development have also been identified.

Sedum emarginatum and its polysaccharide have a therapeutic effect on alcoholic liver disease in mice

Objective: To explore the therapeutic effect of Sedum emarginatum (SE) and its polysaccharide on alcoholic liver disease. Methods: First, we ground fresh SE to obtain homogenate, and then test the effect of SE on a mouse model of acute alcoholic fatty liver disease (AFLD). Kunming female mice were given intragastric administration of alcohol once every 12 hours to induce AFLD, three times in total, and the mice received ethanol and SE at the same time. The mice were sacrificed 4 hours after the last alcohol administration, and serum and liver were collected for testing. We found that SE was effective and then carried out subsequent experiments. The dried SE powder was extracted under heating and reflux by different polar solvents: petroleum ether, ethyl acetate, methanol and water. The extracting solution were heat and concentrated to obtain an extract. The water part was purified to obtain polysaccharide. We tested the therapeutic effect of each part of SE in a mouse model of early alcoholic hepatitis (AH). Mice were given 5 g/kg of alcohol every 12 hours, a total of 9 times, and lipopolysaccharide (LPS) was injected intraperitoneally at the 36 h and 84 h. After 4 hours of the last gavage, the mice were sacrificed. The serum and liver tissue were used to tested relevant biochemical indexes. Results: SE had a certain reversal effect on the increase of serum triglycerides caused by alcohol, and it had a better effect on the accumulation of lipid droplets in liver tissues. Oil red O staining proved this result. In the second acute experiment, the mortality rate of the animal in the model group was 7/12, and the mortality rate in each treatment group was 1/8, 1/7, 4/8, and 1/8. In all parts, the crude polysaccharide did not significantly reverse the increase of serum triglyceride levels in early AH, but it could significantly alleviate the increase of inflammatory foci and steatosis in liver tissue. The transmission electron microscopy result indicates that the crude polysaccharide component has a certain protective effect on mitochondrial damage caused by alcohol. Conclusion: SE can reduce fatty liver and hyperlipidemia caused by alcohol, and its polysaccharide can reduce liver inflammation in the early alcoholic hepatitis by protecting mitochondron.

Acute Kidney Injury in Pregnancy.

Acute kidney injury in pregnancy is a public health problem and a significant cause of maternal and fetal morbidity and mortality. The incidence of pregnancy-related acute kidney injury has increased in the developed countries, theorized to be the result of an increase in pregnancies in advanced maternal age, and continues to remain higher in developing countries owing to inadequate antenatal care. While hyperemesis gravidarum is a common cause of pregnancy-related acute kidney injury during the first trimester, complications such as preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, acute fatty liver disease of pregnancy, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome are important causes of acute kidney injury later in the pregnancy. Diagnosis of pregnancy-related acute kidney injury can be difficult owing to lack of diagnostic criteria and overlapping clinical features between various causes. General measures to treat pregnancy-related acute kidney injury include identification of the underlying cause of kidney injury, intravenous fluid resuscitation, timely initiation of dialysis if needed, and prompt fetal delivery, if necessary. Specific treatment includes steroid and immunosuppressive therapy for glomerulonephritis; prompt delivery for severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and acute fatty liver of pregnancy; and plasmapheresis and eculizumab for thrombotic microangiopathies such as thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome.

Outcomes of liver transplantation for acute fatty liver disease of pregnancy.

Acute fatty liver of pregnancy (AFLP) often resolves after pregnancy delivery but can progress to acute liver failure necessitating liver transplantation. We performed a retrospective review of the national Scientific Registry of Transplant Recipients (SRTR) data to identify all women in the United States undergoing liver transplantation (LT) for acute liver failure (ALF) from AFLP from 1991 to 2015, and compared to outcomes in women of childbearing age undergoing transplant for ALF from acetaminophen and ALF from other etiologies. Women with AFLP were likely to be on life support at time of LT and had high rates of renal dysfunction (median Cr 2.1, IQR 1.2-2.3), and hyperbilirubinemia (median bilirubin 17.1, IQR 11.0, 19.9). Although their early and late LT survival outcomes were comparable to the other indications for LT, cumulative 5-year graft survival was numerically lower among AFLP patients (54%, 95% CI, 27-76) compared to APAP (70%, 95% CI, 63-77) and "Other ALF" (76%, 95% CI, 72-80) groups. In conclusion, although AFLP is a rare indication for LT, AFLP patients were as sick or sicker than other women of childbearing age undergoing LT for ALF. Worsened graft survival may be related to higher rates of rejection in the AFLP group.

Acute fatty liver of pregnancy: A case report of successfully managed an uncommon catastrophic disease

Acute fatty liver disease of pregnancy has universally high fatality rate. But with modern treatment and early anticipation of diagnosis and complication, and with appropriate supportive management it has improved prognosis.

Acute Fatty Liver Disease of Pregnancy: A Review

Acute fatty liver disease of pregnancy (AFLP) is an uncommon but serious obstetrical emergency, usually occurring during the third trimester. The

Acute Fatty Liver Disease of Pregnancy: Updates in Pathogenesis, Diagnosis, and Management.

Acute fatty liver of pregnancy (AFLP) is an obstetric emergency characterized by maternal liver failure and may have complications for the mother and fetus, including death. This review examines recent literature on the epidemiology, pathogenesis, diagnosis, and treatment of acute fatty liver of pregnancy. Pathogenesis of this disease has been linked to defects in fatty acid metabolism during pregnancy, especially in the setting of fetal genetic defects in fatty acid oxidation. The value of screening all patients for these genetic defects remains to be determined. Distinguishing AFLP from other high-risk liver diseases of pregnancy that have overlap features, such as HELLP and preeclampsia, can be challenging. Although sensitive diagnostic tools such as the Swansea criteria have been developed, further work is needed to diagnose AFLP more quickly. Although survival rates have improved in the past 30 years, delay in diagnosis and treatment of AFLP has life-threatening consequences; an algorithmic approach to AFLP may be a valuable resource for clinicians. Future epidemiological and long-term studies will improve our prediction of women at risk for developing AFLP and determine the long-term consequences of this condition.

Protocolo diagnóstico de la elevación de transaminasas en el embarazo

IntroductionAltered liver function tests can be found with a frequency of 3-5% during pregnancy. Although liver disease during pregnancy is rare, its early identification is important due to possible comorbidities and increased fetal o maternal mortality. EtiologyLiver disease during pregnancy can be classified into two major groups: those directly caused by pregnancy (HELLP syndrome or acute fatty liver disease) and those co-existing with pregnancy (unknown pre-existing liver disease or acute liver disease). The most common causes are viral hepatitis that have a similar course in non-pregnant patients. An alteration of transaminases should be assessed to establish a diagnosis as soon as possible for prognostic implications.

A Case of Term Pregnant Woman with Pseudothrombocytopenia: An Overlooked Phenomenon

Objective: To report a case of pregnant woman with low thrombocyte count which in fact has spurious thrombocytopenia. Methods: A 40-week pregnant woman was admitted to our obstetric clinic with complaint and signs of active labour. She was hospitalized and followed for the vaginal birth. Results: On laboratory examination, the low platelet (Plt) count as 42 x 103/mm was measured by using blood samples with ethylenediaminetetraacetic acid (EDTA). Patient had no history for echymosis, bleeding disorders and bruising. She underwent a differential diagnosis for thrombocytopenia in term pregnancy for preeclampsia, HELLP syndrome, acute fatty liver disease or immune thrombocytopenic purpura and no pathology was found. The peripheral blood smear showed platelet (plt) clustering with normal count as 181 x 103/mm. She diagnosed as pseudothrombocytopenia. The patient delivered a healthy baby with vaginal way and had no bleeding complication in pospartum period. Conclusion: Thrombocytopenia in pregnancy is a challenging and important issue for obstetrician. Case Report Erbil and Kamuran; BJMMR, 6(12): 1196-1200, 2015; Article no.BJMMR.2015.299 1197 We aimed to point out that low Plt count doesn’t indicate always a serious disease in term pregnancy. Pseudothrombocytopenia should be kept in mind which may cause unnecessary laboratory examination and treatments.

A case of acute viral hepatitis interfering with acute fatty liver disease of pregnancy

Acute hepatitis A is a rarely seen infection during preg­nancy. In terms of clinical and laboratory findings, it can be interfere with acute fatty liver disease which can be quite mortal during pregnancy. Since liver function tests are el­evated in both conditions, hepatitis A infection should also be kept in mind in differential diagnosis. We present a 30 year-old pregnant woman with 35 weeks of gestation who presented to our clinic with a suspection of acute fatty liver disease but finally diagnosed as acute hepatitis A in­fection.

Atteinte hépatique gravidique : mode de révélation d’une anomalie de la bêta-oxydation des acides gras chez l’enfant

Acute fatty liver of pregnancy (AFLP) and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome are serious maternal illnesses occurring in the third trimester of pregnancy with significant perinatal and maternal mortality. AFLP may result from mitochondrial defects in the beta-oxidation of fatty acids, in particular a deficiency of the long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) in the fetus. Clinical findings in AFLP vary and its diagnosis is complicated by a significant overlap in clinical and biochemical features with HELLP syndrome. We report the case of 2 siblings who died, the first one in the neonatal period of asphyxia with multivisceral presentation and the second one from sudden death at 7 months. Autopsy of the latter infant revealed hepatic steatosis associated with cardiomyopathy, which led to suspicion of a fatty acid oxidation deficiency. Mutation analysis demonstrated that both children were homozygous for the common mutation c.1528G>C and the parents were heterozygous for this same mutation. This case demonstrates the importance of screening mothers with acute fatty liver disease of pregnancy and their children at birth for a metabolic disease. This article proposes several metabolic tests for mother and child suspected of having beta-oxidation of a fatty acid disorder.

Pregnancy-associated acute liver disease and acute viral hepatitis: Differentiation, course and outcome

Pregnant women with acute viral hepatitis (VH) and those with pregnancy associated acute liver disease (PAALD) including acute fatty liver disease of pregnancy, hemolysis elevated liver enzyme and low platelet syndrome present with similar clinical features and liver tests abnormalities. Accurate differentiation between the two groups is critical to expedite early delivery in the latter and prevent progressive liver damage. There is scant data in the literature to differentiate between PAALD and VH. We studied the clinical variables, hematological, biochemical and viral serological tests of 87 consecutive pregnant patients with jaundice from 2000 to 2003. There were 46 and 41 patients in PAALD and VH group, respectively. Two-thirds in VH group were due to hepatitis E. Univariate analysis identified hypertension, encephalopathy, oliguria, ascites, serum creatinine, and low platelets as significantly more common in the PAALD group. Multivariate analysis and recursive partitioning identified hypertension and ascites as predictors of PAALD with excellent predictive ability and c value of 0.92. Mortality was 41% in PAALD and 7.5% in VH. Increased bilirubin and oliguria were predictors of mortality in PAALD. Presence of ascites and hypertension differentiates PAALD from VH and should prompt early delivery. Mortality due to hepatitis E is low.

Hepatitis E and jaundice in an HIV-positive pregnant woman

Hepatitis E and jaundice in an HIV-positive pregnant woman