Description

• A rare but serious obstetrical diagnosis associated with significant maternal and neonatal morbidity and mortality
• Due to a fetal/placental defect in β-oxidation of fatty acids, toxic metabolites accumulate in the circulation and cause a microvesicular fatty infiltration in maternal hepatocytes.
• This microvesicular fatty infiltrate of the liver leads to significant liver dysfunction and may cause irreversible fulminant liver failure.
• The most reported and studied fetal fatty acid oxidation defect that is linked to acute fatty liver of pregnancy (AFLP) is long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD).
• System(s) affected: hepatorenal, hematologic, central nervous system, gastrointestinal, pulmonary, endocrine (pancreas)
• Synonym(s): obstetric acute yellow atrophy; acute yellow atrophy of the liver

Epidemiology

Incidence
Ranges from 1 in 7,000 to 1 in 16,000 pregnancies (1)[C]

Etiology and Pathophysiology

• Usually presents during the 3rd trimester after 30 weeks’ gestational age but can occur as early as 22 weeks’ gestational age (1)[C]
• Abnormal fetal mitochondrial β-oxidation of fatty acids leads to AFLP in the mother.
• LCHAD is the most frequent fetal diagnosis but AFLP can occur with any fetal fatty acid oxidation defect.
• Women with heterozygous LCHAD defect have a higher risk of developing AFLP if carrying an infant with a homozygous LCHAD defect due to the increased metabolites produces by the fetus and decreased capabilities of the mother to oxidize them.

Genetics
Autosomal recessive mutation in LCHAD

Risk Factors

• Prior pregnancy complicated by AFLP
• Family history of a child with a fatty acid oxidation disease
• Multiple gestation
• Coexisting diagnosis of liver disease
• Male fetus
• Women with heterozygous LCHAD defect

General Prevention

A diet low in long-chain fatty acids and supplemented with medium-chain triglycerides if LCHAD deficiency is present (2)[C]

Commonly Associated Conditions

20–40% of patients who have AFLP have HELLP, and 20% have preeclampsia. Eclampsia, ICP, and hyperemesis gravidarum have a weak association with AFLP (1)[C].

Physical Exam

• Prodromal symptoms of malaise followed by nausea and vomiting
• Jaundice, coagulopathy, encephalopathy, ascites
• Dehydration (dry mucous membranes, poor skin turgor, delayed capillary refill)
• Anorexia
• Right upper quadrant/epigastric pain
• Headache
• Dark urine, oliguria, anuria, polyuria, polydipsia
• Hypertension, multiple organ failure

Differential Diagnosis

• Gastroenteritis
• Cholestasis
• Cholecystitis
• Preeclampsia/eclampsia
• HELLP syndrome
• Intrahepatic cholestasis of pregnancy
• Viral hepatitis
• Autoimmune hepatitis
• Drug-induced or toxic hepatitis

Diagnostic Tests & Interpretation

Initial Tests (lab, imaging)

• Transaminitis to 5 to 10 times the upper limit of normal (AST, ALT usually <1,000)
• Elevated total and direct bilirubin (>5 mg/dL)
• Thrombocytopenia
• Decreased fibrinogen
• Elevated D-dimer and fibrin split products
• Prolonged prothrombin time (PT), PTT, and INR
• Leukocytosis
• Elevated ammonia
• Elevated uric acid
• Elevated BUN and creatinine
• Elevated lactate dehydrogenase
• Hypoalbuminemia
• Hypoglycemia
• Metabolic acidosis, lactic acidosis
• Proteinuria

Diagnostic Procedures/Other

• The gold standard is a liver biopsy revealing microvesicular steatosis. This is rarely used for diagnosis especially in the clinical setting of coagulopathies.
• The Swansea criteria is a proposed diagnostic tool by Ch’ng et al (3)[B]. It has a sensitivity of 100%, a specificity of 57%, a positive predictive value of 85%, and a negative predictive value of 100% (1)[C].
• Swansea criteria (3)[B]: presence of 6 out of the 14 criteria in the absence of an alternate diagnosis:
  • Vomiting
  • Abdominal pain
  • Polydipsia/polyuria
  • Encephalopathy
  • Elevated bilirubin
  • Hypoglycemia
  • Elevated uric acid
  • Leukocytosis
  • Elevated transaminases
  • Elevated ammonia
  • Renal impairment
  • Coagulopathy
  • Ascites or bright liver on ultrasound
  • Microvesicular steatosis on liver biopsy
• Since this study was initially published, other authors have suggested requiring 9 out of the 14 criteria to diagnose AFLP.
• Ultrasound is preferred over computed tomography (CT) due to maternal and fetal radiation risks associated with CT. There is no statistical difference for AFLP diagnosis between CT and ultrasound (4)[C].
• Abnormal levels of PT, plasma fibrinogen, and platelet count correlate with recovery. Leukocyte count, blood glucose, and AST/ALT do not have predictive value (1)[C].

General Measures

• Continuous maternal and fetal monitoring
• Emergent delivery of fetus
• Consider cesarean section if remote from vaginal delivery; must take into consideration maternal condition, fetal condition, and risk of bleeding (4)[C]
• Supportive treatment for liver failure, multiorgan failure
• Monitor serial labs, urine output.
• Intravenous fluids to ensure adequate hydration while monitoring for fluid overload
• Treat coagulopathy with blood products as needed.
• Correct electrolyte and acid–base disturbances.
• Treat neonatal conditions associated with prematurity.
• Monitor neonate for features of fatty acid oxidation defects.

Medication

As indicated for delivery, treatment of liver and multiorgan failure and neonate. Consider broad-spectrum antibiotics for gram-negative bacteria to prevent sepsis (5)[C].

Admission, Inpatient, and Nursing Considerations

Treatment requires intensive care treatment at a tertiary care center and a multidisciplinary approach.

Follow-up Recommendations

• Continue to follow liver panel, chemistries, renal function, coagulation panel, complete blood count postpartum. Abnormalities can peak as late as postpartum day 2.
• Clinical symptoms improve over days to weeks postdelivery.
• LFTs may begin to trend downwards 1 to 2 days after delivery; bilirubin after 3 to 4 days
• Acute kidney injuries generally resolve in 7 to 10 days.
• Liver abnormalities can take months to normalize.
• Consider genetic testing for future pregnancies as recurrence risk is 25%.
• Be wary of prescribing contraceptives or other liver toxic drugs.
• The neonate should be tested for LCHAD and other fetal fatty acid oxidation deficiencies after delivery.

Prognosis

• AFLP is usually reversible if diagnosed and treated early and aggressively.
• Maternal mortality rate <10–15%
  • Death secondary to sepsis, acute liver failure with encephalopathy, acute renal failure, cardiac failure, pancreatitis, gastrointestinal bleed, DIC
• Fetal mortality rate 20%
• If the mother and child survive, full clinical recovery usually occurs over several weeks (1)[C].
• Neonatal morbidity risks also stem from prematurity and intrauterine growth restriction.
• Risk in subsequent pregnancies is 25% if the fetus has LCHAD deficiency (2)[C].
• Postpartum bleeding occurs in 50% of AFLP patients.

Complications

• Coagulopathy: postpartum hemorrhage
• Disseminated intravascular coagulation
• Hepatic encephalopathy
• Acute renal failure
• Sepsis
• Pancreatitis
• Pulmonary edema
• Preeclampsia, eclampsia
• Multiple organ failure
• Hypoglycemia
• Diabetes insipidus
• Maternal and/or fetal demise

ICD-10

• K76.0 Fatty (change of) liver, not elsewhere classified
• O26.611 Liver and biliary tract disord in pregnancy, first trimester
• O26.612 Liver and biliary tract disord in preg, second trimester
• O26.613 Liver and biliary tract disord in pregnancy, third trimester
• O26.619 Liver and biliary tract disord in pregnancy, unsp trimester

ICD-9

• 571.8 Other chronic nonalcoholic liver disease
• 646.70 Liver and biliary tract disorders in pregnancy, unspecified as to episode of care or not applicable
• 646.73 Liver and biliary tract disorders in pregnancy, antepartum condition or complication

SNOMED

• 91162000 necrosis of liver of pregnancy (disorder)