Acute Fatty Liver of Pregnancy

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Diagnosis and reasoning

This primiparous lady has presented with jaundice during the third trimester; this is an extremely concerning finding which mandates further evaluation. The causes of jaundice in pregnancy can be broadly classified into conditions related to pregnancy, pre-existing conditions exacerbated by pregnancy, and conditions incidental to pregnancy. Considering her gestational age, key pregnancy related conditions to consider include intrahepatic cholestasis of pregnancy (ICP) and acute fatty liver of pregnancy (AFLP); the history of hypertension makes preeclampsia and/or HELLP syndrome an additional possibility. Gallstone disease exacerbated by pregnancy is another consideration; in addition, viral hepatitis may occur in any trimester, and is by far the commonest cause of jaundice during pregnancy. ICP is clinically less likely, given the absence of pruritus (which is typically a prominent finding in such patients); note also that in ICP, the serum bilirubin is usually < 5 mg/dl, while transaminases are minimally elevated, if at all. Acute viral hepatitis is also unlikely, as transaminase levels are usually significantly higher in such patients (often > 500 U/L); the negative hepatitis screen definitively excludes this possibility. Cholelithiasis is also unlikely, given the absence of gallstones on the ultrasound scan (although acalculous cholecystitis remains a rare possibility). The absence of proteinuria excludes preeclampsia (in which this is a cardinal feature); in addition, a full blood count shows normal platelet levels and no features of hemolysis, excluding HELLP syndrome. The moderate elevation of transaminases and bilirubin levels, and hypoalbuminemia is compatible with AFLP; the presence of marked hypoglycemia in the metabolic panel, and the severe coagulopathy is further in favor of this diagnosis, as is the sonographic evidence of fatty changes in the liver. AFLP is a high-risk state; she should be transferred to an intensive care unit for urgent supportive management; vitamin K should be administered to help correct the coagulopathy. Once she is stabilized, the fetus should be delivered as soon as possible; given the poor maternal status, cardiotocogram suspicious of fetal compromise, and low Bishop's score (indicating that induction is less likely to be successful), cesarean section is probably the best mode of delivery.


Discussion

Acute fatty liver of pregnancy (AFLP) is a rare, potentially life threatening condition unique to pregnancy, which is characterized by microvesicular steatosis in the liver. The incidence ranges from 1 in 7,000 to 1 in 16,000 pregnancies; most cases occur in the 3rd trimester, although the disease can occur at any time in pregnancy. Overall, AFLP is more common in primigravidas, multiple pregnancies, and in pregnancies carrying a male fetus. The exact pathogenesis is still unclear; however, defective fetal fatty acid metabolism is believed to play a causative role. The clinical presentation depends on the severity of the disease; the most common symptoms are nonspecific and include anorexia, nausea, vomiting, malaise, fatigue, headache and abdominal pain; fever may also be present. Jaundice usually develops after a few days; examination may reveal tenderness in the right upper quadrant, although the liver is usually impalpable. With advanced disease, liver failure occurs; acute renal failure, encephalopathy, gastrointestinal bleeding, pancreatitis and disseminated intravascular coagulation (DIC) may also develop. Preeclampsia may occur in some of these patients, who may thus be edematous, with hypertension and proteinuria. Investigations usually reveal abnormal liver biochemistries; modest elevation of transaminases is common, with values between 300 to 500 U/L typically being seen, although levels can rise to as high as 1000 U/L. Hyperbilirubinemia ranging from 3 to 25 mg/dL is also common; alkaline phosphatase (ALP) can also be markedly elevated, although this is often difficult to distinguish from the normal elevation of ALP encountered in late pregnancy. As the disease progresses, profound hypoglycemia may develop, due to impaired hepatic gluconeogenesis. A coagulation profile may reveal prolonged prothrombin (PT) and partial thromboplastin (APTT) times, as well as low fibrinogen levels; disseminated intravascular coagulation (DIC) occurs in up to 70% of patients. Other associated abnormal laboratory findings include: raised serum ammonia and amino acid levels, severe lactic acidosis, raised uric acid levels, and impaired renal functions. Imaging studies do not play a role in confirming the diagnosis, but may provide important supporting evidence; ultrasonography may show a fatty liver, while computerized tomography (CT) may show decreased or diffuse attenuation of the liver tissue. Liver biopsy is the gold standard for diagnosis; however this is rarely performed, as it is invasive, and prone to complications in the presence of coagulopathy. AFLP is an obstetric emergency; first and foremost, the mother should be managed in an intensive care setting and stabilized. Particular attention should be paid towards airway management, treatment of any hypertension, and correction of hypoglycemia, electrolyte or acid-base imbalances, and extant coagulation abnormalities. Definitive management requires delivery of the fetus, irrespective of gestational age; this should only be attempted following maternal stabilization. While the exact mode of delivery depends on the age of gestation and maternal and fetal statuses, in practice, caesarean section is often performed. It is essential to appreciate that these patients are at high risk of developing potentially fatal complications even following delivery; these include respiratory failure, sepsis, renal failure, nephrogenic diabetes insipidus, gastrointestinal hemorrhage, and severe bleeding due to coagulopathy, DIC and pancreatitis. Special attention should be paid to serum glucose levels, as these patients are at risk of developing sudden, severe hypoglycemia. Most patients recover completely a few days following delivery; however, maternal mortality can be as high as 18% of all cases, with the aforementioned complications being the main causes of death. The fetal mortality rate is even higher, being approximately 25%; thus, continuous fetal monitoring and neonatal care is essential.


Take home messages

  1. AFLP is a rare, life-threatening cause of jaundice in pregnancy.
  2. The diagnosis of AFLP is extremely tricky; the clinical and laboratory manifestations may overlap with those of HELLP syndrome and preeclampsia.
  3. Definitive management requires delivery of the fetus, irrespective of gestational age.
  4. While most patients recover within a few days after delivery, it is essential to appreciate that they are still at risk of complications during the immediate postpartum period.

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