Acute Fatty Liver of Pregnancy: Rare, but Potentially Fatal

Background

Acute fatty liver of pregnancy (AFLP) is a rare but potentially fatal disease. The pathophysiology of AFLP remains unknown, but there is some evidence of an association with fatty acid oxidation defects during pregnancy. This condition usually occurs between 30 and 38 weeks of gestation. The clinical signs are nonspecific, with the most frequent symptoms being nausea, vomiting, abdominal pain, and jaundice [1]. This pathology remains an obstetric emergency, requiring early diagnosis and treatment, which currently consists of termination of pregnancy and supportive therapy. Disseminated intravascular coagulation (DIC) is one of the most frequent complications [2,3]. We present a case that was diagnosed early and consequently had a good maternal and fetal prognosis.

Case Report

A 34-year-old, nulliparous, healthy woman, at 37 weeks and 2 days’ gestation, came to the Emergency Department for loss of amniotic fluid. She also referred to nausea and vomiting with 4 days of evolution, associated with prostration since that day. She denied pruritus, headache, epigastric pain, or visual impairment. Pregnancy was monitored without inter-currences. She had no history of travel or ingestion of drugs or medicinal herbs. On admission, the patient was uncooperative, icteric, apyretic, with blood pressure of 118/74 mmHg and lower-limb edema. The analytical study showed hemoglobin 11.5 g/dl, white blood cell count of 29.60×103/uL with neutrophilia (81.2%) and lymphocytosis (13.5%), platelet count 146×103/uL, serum lactate dehydrogenase 1114 U/L, aspartate aminotransferase 273 U/L, alanine aminotransferase 370 U/L, alkaline phosphatase 419 U/L, total bilirubin 8.21 mg/dl, bile acids 3.3 mol, serum creatinine 1.69 mg/dl, urea 42 mg/dl, albumin 24 g/L, glucose 59 mg/dl, prothrombin time 32.7 s, and activated partial thromboplastin time of 59.9 s. Hepatitis A, B, C, and E serology were negative. Abdominal ultrasonography revealed “liver with a slight increase of the right lobe, admitting a discrete diffuse heterogeneity with a slight increase in echogenicity, translating diffuse steatosis” (Figure 1). A presumptive diagnosis of acute fatty liver of pregnancy was made. The patient was admitted to the delivery room and, due to fetal distress, underwent an emergency cesarean section. The newborn male, weighing 2810 g, had an Apgar score of 3 at the first minute and 5 at the fifth minute, requiring resuscitation. In the postoperative period, the patient was transferred to the Intensive Care Unit (ICU) for treatment and stabilization of acute hepatic and renal insufficiency and disseminated intravascular coagulation (DIC). She required continuous infusion of 5% dextrose for about 10 days to maintain euglycemia. On the 7th day of hospitalization, due to nausea and vomiting and elevation of amylase (260 U/L) and lipase (948 U/L), she underwent abdominal CT, which revealed “discrete globosity of the pancreatic parenchyma, with dimensions at the upper limit of normality”, and acute pancreatitis was diagnosed. She was progressively able to eat, up to the date of discharge. She presented progressive improvement of the analytical parameters of hepatic function (Table 1). Due to DIC, she underwent therapy with fresh frozen plasma, fibrinogen, and vitamin K. She was discharged, clinically improved, on the 22nd postnatal day.

Discussion

AFLP is a rare disease, which usually develops in the third trimester of pregnancy [1]. Its incidence ranges from 1: 7000–15 000 pregnancies [4]. Several risk factors were identified, being more frequent in nulliparas and with male fetuses, as in our case. Other associated risk factors are: previous episode of acute fatty liver of pregnancy, multiple pregnancy, body mass index less than 20 kg/m2, fetal long-chain 3-hydroxyacyl CoA dehydrogenase deficiency, and preeclampsia [5,6]. The pathogenesis of AFLP can be associated with defects in fatty acid metabolism during pregnancy. LCHAD (long-chain 3-hydroxyacyl CoA dehydrogenase) is one of the most commonly affected enzymes. Fetuses with this homozygous defect lead to the accumulation of intermediate products of fatty acid metabolism, which have deleterious effects on maternal hepatocytes [7]. Patients can develop nonspecific symptoms, such as nausea and vomiting, abdominal pain, and jaundice, which progress rapidly to acute liver failure, marked by complications such as coagulopathy, hypoglycemia, and renal failure [1,8]. Rarely, some patients develop pancreatitis [9]. The differential diagnosis should include other diseases, such as pre-eclampsia, HELLP syndrome (hemolysis, elevated liver enzyme levels, and low platelet levels), intrahepatic cholestasis of pregnancy, viral hepatitis, and drug-induced hepatitis. In intrahepatic cholestasis of pregnancy, the predominant symptom is pruritus, with serum bilirubin less than 5 mg/dl and elevated bile acids. AFLP can be distinguished from HELLP syndrome and preeclampsia by hypoglycemia, jaundice, and by signs of systemic hepatic dysfunction such as mild-to-moderate elevation of transaminases, hepatic encephalopathy, and DIC [8]. Viral hepatitis usually has higher aminotransferase values. This pathology was excluded through serologies that turned out to be negative. The use of drugs or medicinal herbs was also excluded by the anamnesis. Other differential diagnoses were excluded based on symptomatology and complementary means of diagnosis. There is no universal approach to diagnosis, and clinical, laboratory and imaging findings, as well as Swansea criteria, should be considered when clinical suspicion is present [5] (Table 2). Our patient had vomiting, bilirubin >0.8 mg/dl, hypoglycemia <72 mg/dl, leukocytes >11×109/L, alanine aminotransferase >42U/L, and coagulopathy with prothrombin time >14 s, fulfilling 6 criteria. Imaging tests may be helpful in supporting the diagnosis of AFLP, but their role remains unclear [10]. In the present case, the ultrasound scan presented diffuse hepatic steatosis, which is neither a specific result nor a diagnosis [2]. Liver biopsy should only be used when the diagnosis is doubtful [1]. The recommended treatment is the interruption of pregnancy. The mode of delivery depends on the degree of maternal and fetal decompensation and the probability of successful vaginal delivery. Women who require treatment often need to be admitted to the ICU for coagulopathy reversal, ventilation, correction of hypoglycemia, and renal failure [1]. Another possible complication is pancreatitis, so it is important to measure amylase and lipase after suspected AFLP. CT may be useful in this complication. Maternal mortality rates have improved in recent decades, with global mortality now being below 10% [11]. Currently, it is possible to carry out the genetic study of LCHAD deficiency. However, negative tests for the most common mutation, G1528C, do not exclude the condition. In the presence of the enzymatic defect, the newborn’s prognosis depends mainly on the clinical manifestations; therefore, molecular diagnosis is not routinely performed at our center unless clinically suspected [7]. There is a possibility of recurrence of this condition in subsequent pregnancies, although the exact risk is unknown [12].

Conclusions

Decreased maternal and fetal mortality are associated with early recognition of this pathology and timely action in a context of differentiated care.