Acute fatty liver disease of pregnancy

Résumé fourni par la source

EPIDEMIOLOGY Acute fatty liver of pregnancy (AFLP), originally known as “acute yellow atrophy of the liver,” is an obstetrical and medical emergency that is characterized by microvesicular fatty infiltration of hepatocytes.1 AFLP is rare, with studies demonstrating incidences ranging from 1 in 4000 to 1 in 20,000 pregnancies.2–6 Despite its infrequency, it is critical to be able to diagnose and manage this condition promptly due to its high perinatal and maternal mortality rates. AFLP is associated with prior AFLP, nulliparity (a pregnancy in a woman that has never given birth), low body mass index, male gender of the fetus, and multiple pregnancies (a pregnancy with more than 1 fetus).2,6–8 AFLP is strongly linked with fetal fatty acid oxidation defects, though the precise pathophysiology is unknown. Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is most commonly associated with AFLP.9,10 One study showed up to a 50-fold increased risk of maternal liver disease (either AFLP or HELLP [hemolysis, elevated liver enzymes, and low platelets syndrome]) in infants with an LCHAD deficiency.11 Homozygous LCHAD deficiency in the fetus leads to the inability to perform mitochondrial beta-oxidation of fatty acids, resulting in the accumulation of long-chain 3-hydroxy fatty acids that pass from the fetal to maternal circulation.12 Maternal factors of heterozygous LCHAD status, the placental release of long-chain 3-hydroxy fatty acids, increased production of fatty acids during pregnancy, and decreased maternal beta-oxidation of fatty acids, especially in the third trimester likely also contribute to the pathogenesis of AFLP.12,13 Fatty acid accumulation in the hepatocyte mitochondria produces reactive oxygen species and microvesicular steatosis, resulting in maternal hepatotoxicity (Figure 1).12 This typically presents as AFLP, though HELLP has also been associated with LCHAD deficiencies through a similar mechanism.11,14 After birth, LCHAD deficiencies in the infant can present as severe hypoglycemia, myopathies, and multiorgan failure. Due to this strong association, it is imperative for infants of mothers with AFLP to be tested for LCHAD deficiencies.12,13FIGURE 1: Overview of AFLP Pathophysiology. Created with Biorender.com. Abbreviations: AFLP, acute fatty liver of pregnancy; BMI, body mass index.NATURAL HISTORY AFLP typically occurs in the third trimester of pregnancy or postpartum, with a median presentation of 35–37 weeks. However, cases can still manifest before the third trimester.2,3,6–8,15 The most common presenting symptoms are nausea and emesis, though patients may also experience epigastric pain, malaise, jaundice, polydipsia, polyuria, and in cases that present as acute liver failure (ALF), encephalopathy (Figure 2).2,6,7,16 Hypertension or preeclampsia can occur concomitantly. For any patient in the third trimester with a new onset of nausea and emesis, AFLP must be considered.6FIGURE 2: Clinical Symptoms of AFLP. Created with Biorender.com. Abbreviation: AFLP, acute fatty liver of pregnancy.Lab abnormalities are significant for evidence of liver dysfunction and can distinguish AFLP from other liver disorders of pregnancy.17 Patients with AFLP typically have elevated transaminases (300–1000), bilirubin, lactate dehydrogenase, and prothrombin time, with low platelets, fibrinogen, and antithrombin III.17,18 Almost all patients present with acute kidney injury (AKI) early in the disease course, which can differentiate AFLP from other syndromes. In severe liver dysfunction or ALF, hypoglycemia and severe coagulopathy with complications of disseminated intravascular coagulation can occur. It is important to be able to distinguish AFLP from preeclampsia/eclampsia and HELLP as immediate delivery is indicated in AFLP, and if progression to ALF occurs, liver transplant must be considered. Maternal mortality rates with AFLP have decreased from 80% to 90% before 1970 to less than 10% more recently due to rapid delivery.16,19 AFLP and HELLP can present with similar symptoms, including elevated transaminases, preeclampsia/eclampsia, and proteinuria within the same pregnancy time frame (Table 1). One study compared the presentation findings of the syndromes and found that AFLP predominantly presented with nausea, vomiting, jaundice, and AKI, while HELLP initially presented with headache and abdominal pain without AKI.18 Importantly, coagulopathy is caused by liver dysfunction in AFLP, while in HELLP, it is initially caused by hemolysis, though in rare instances, HELLP can also progress to liver failure.2 In addition, although both have similar lab findings, patients with AFLP are found to have higher white blood cell count and lower glucose, cholesterol, triglyceride, antithrombin, and fibrinogen levels than patients with HELLP.6,18,20,21 It is imperative to distinguish between these diseases because initial treatment differs for the 2 syndromes, even though delivery is often the ultimate management for both (Figure 3). TABLE 1 - Comparison of AFLP and HELLP AFLP HELLP Risk factors Nulliparity, multiple pregnancy, low BMI, male sex of the fetus, prior AFLP Multiparity, history of diabetes, hypertension, advanced maternal age, and prior HELLP Trimester presentation Third trimester and can occur in postpartum Second or 3rd trimester and can occur in postpartum Typical clinical symptoms Nausea, emesis, malaise, epigastric pain, jaundice, and hypertension Headache, epigastric pain, and hypertension Initial lab abnormalities AKI, leukocytosis, thrombocytopenia, elevated AST/ALT, and LDH, prolonged PT, hyperbilirubinemia, hypoglycemia, low fibrinogen, and proteinuria Proteinuria, leukocytosis, thrombocytopenia, elevated AST/ALT, elevated LDH, and hyperbilirubinemia Differences in labs abnormalities AKI, worse leukocytosis and hyperbilirubinemia, prolonged PT, lower fibrinogen and antithrombin Higher LDH, worse thrombocytopenia, and markers of hemolysis (anemia, low haptoglobin, schistocytes present) Maternal complications Ascites, encephalopathy, DIC AKI, placental abruption, eclampsia Maternal prognosis Mortality of 10%–17% or lower with immediate recognition and delivery Mortality of 1%–2% or lower with immediate recognition and delivery Fetal prognosis Estimated up to 20%–25% mortality Estimated up to 20%–25% mortality Risk of recurrence Low but elevated risk of recurrence Low but elevated risk of recurrence Abbreviations: AFLP, acute fatty liver of pregnancy; AKI, acute kidney injury; ALT, alanine transaminase; AST, aspartate transaminase; BMI, body mass index; DIC, disseminated intravascular coagulation; HELLP, hemolysis, elevated liver enzymes, and low platelets syndrome; LDH, lactate dehydrogenase; PT, prothrombin. FIGURE 3: Diagnostic Schema for AFLP. Created with Biorender.com. Abbreviations: AFLP, acute fatty liver of pregnancy; ALT, alanine transaminase; AST, aspartate transaminase; BMP, basic metabolic panel; CBC, complete blood count; Crt, creatinine; HELLP, hemolysis, elevated liver enzymes, and low platelets syndrome; INR, international normalized ratio; LDH, lactate dehydrogenase; PT, prothrombin; PTT, partial thromboplastin time; UA, urinalysis; WBC, white blood cell count.DIAGNOSIS The Swansea Criteria are used to bring uniformity to the diagnosis of AFLP. They are defined by 6 or more of the following: vomiting, abdominal pain, polydipsia/polyuria, encephalopathy, aspartate transaminase or alanine transaminase > 42 U/L, bilirubin > 0.8 mg/dL, glucose < 72 mg/dL, white blood cell count > 11 × 106/L, uric acid > 5.7 mg/dL, ammonia > 42 IU/L, creatinine > 1.7 mg/dL, prothrombin > 14 sec or partial thromboplastin time > 34 sec, ascites or bright liver on ultrasound, or microvesicular steatosis on biopsy.4 The criteria have an estimated sensitivity of 100% and a specificity of 57%, with a positive predictive value of 85% and a negative predictive value of 100%, and were validated in a prospective study.2,22 Notably, the Swansea Criter

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.