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INTRODUCTION

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Acute fatty liver of pregnancy (AFLP) is an uncommon but potentially fatal complication of pregnancy, which results in microvesicular fat deposition in the liver, resulting in severe liver dysfunction. Hallmarks of the disease include jaundice, coagulopathy, and encephalopathy. Although most commonly a disorder of the late third trimester, very rare cases have been reported as early as 23 weeks. The incidence of AFLP appears to have increased over the past 30 years (from 1:15,900-1:6692 deliveries), possibly as more widespread recognition of the disease and identification of milder cases occurs. Prior to the 1970s, maternal and fetal mortality rates were reported to be as high as 75% and 85%, respectively. However, recent reports suggest markedly improved maternal mortality, ranging from 0% to 10% and fetal mortality from 8% to 25%. Deaths have been attributed to bleeding complications, aspiration, renal failure, and sepsis. Survivors of AFLP generally recover without sequelae. Early diagnosis is critical and AFLP should be considered in all pregnant women presenting in the third trimester of pregnancy with nausea, vomiting, or epigastric pain.

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PATHOPHYSIOLOGY

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The precise etiology of AFLP remains unknown. However, in some cases, an autosomal recessive fetal enzyme deficiency involved in the mitochondrial fatty acid oxidation pathway has been linked to the development of maternal AFLP. The largest study to date of 27 women affected by AFLP found that 19% of the offspring of these pregnancies had long-chain 3-hydroxyacyl coenzyme dehydrogenase (LCHAD) deficiency. In contrast, no newborns had LCHAD deficiency when 81 maternal HELLP hemolysis, elevated liver transaminases, low platelets syndrome (HELLP syndrome) cases were evaluated. It is postulated that toxic metabolites, such as free fatty acids from an impaired fetoplacental unit, result in maternal illness in these cases of AFLP. Recently in fact, placentas of women who had AFLP were shown to have impaired mitochondrial function, resulting in free radical production and fatty acid accumulation, generating oxidative stress. Importantly, LCHAD deficient infants are at subsequent risk for hepatic steatosis, hypoglycemia, coagulopathy, coma, and death, all of which can be prevented with the use of a special diet and frequent regular feeding. It has been recommended that newborns of all women with AFLP should undergo molecular analysis for LCHAD gene mutations. Nationally, all states have now implemented LCHAD and other fatty acid enzyme disorder testing as part of routine newborn screening via tandem mass spectrometry. Abnormal LCHAD function may represent only one of a variety of fatty acid metabolic disorders resulting in the clinical phenotype of AFLP.

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The pathway of impaired mitochondrial oxidation has been implicated in other microvesicular liver disorders in nonpregnant individuals that are remarkably similar to AFLP. Exogenous impairment of mitochondrial oxidation can occur with ingestion of aspirin, valproic acid, and tetracycline, and would, in susceptible individuals with latent oxidative enzyme deficiencies, result in liver dysfunction, such as is seen in Reyes disease, tetracycline toxicity, and valproic acid injury. Common histopathologic findings include the presence of ...

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