BASICS
DESCRIPTION
- A rare but serious diagnosis associated with significant maternal and neonatal morbidity and mortality
- Microvesicular fatty infiltrate of the liver occurring during pregnancy
- Is often associated with an inherited defect in mitochondrial β-oxidation of fatty acids, long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD). This defect in LCHAD causes toxic hydroxyl fatty acid metabolites to accumulate and cause microvesicular fatty infiltration in hepatocytes.
- In fetuses with homozygous defect in LCHAD, the unoxidized fatty acids are transferred to the mother via the placenta.
- System(s) affected: hepatorenal, central nervous system, pulmonary, endocrine (pancreas), and hematologic
- Synonym(s): obstetric acute yellow atrophy; acute yellow atrophy of the liver
EPIDEMIOLOGY
Incidence
1 in 10,000 pregnancies (range of 1/7,000 to 1/16,000) (1)
ETIOLOGY AND PATHOPHYSIOLOGY
- 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.
- Usually presents during the 3rd trimester (mean 36 weeks) when the highest release of fatty acids from the placenta occurs (2).
- Abnormal fetal mitochondrial β-oxidation of fatty acids leads to AFLP in the mother (1).
Genetics
Autosomal recessive mutation in LCHAD
RISK FACTORS
- Prior pregnancy complicated by AFLP
- Loss of a child before age 2 years
- History of a child with Reye syndrome
- Family history of a child with a fatty acid oxidation disease
- Multiple gestation (>14-fold increase in risk) (3)
- Preeclampsia in current or prior pregnancies
- Male fetus
GENERAL PREVENTION
A diet low in long-chain fatty acids and supplemented with medium-chain triglycerides if LCHAD deficiency is present (4)[C].
COMMONLY ASSOCIATED CONDITIONS
HELLP, preeclampsia, eclampsia, ICP, hyperemesis gravidarum
DIAGNOSIS
PHYSICAL EXAM
- Prodromal symptoms of malaise followed by nausea and vomiting
- Hypoglycemia
- Metabolic acidosis, lactic acidosis
- Jaundice
- Encephalopathy
- Ascites
- Dehydration (dry mucous membranes, poor skin turgor, delayed capillary refill)
- Anorexia
- Right upper quadrant/epigastric pain
- Coagulopathy leading to increased bleeding time and spontaneous bleeding
- 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
- Drug-induced or toxic hepatitis
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Mild to moderate transaminitis (AST, ALT elevated to mean of 200)
- Elevated total and direct bilirubin
- Thrombocytopenia
- Decreased fibrinogen
- Elevated D-dimer and fibrin split products
- Prolonged PT, PTT, and INR
- Leukocytosis
- Elevated ammonia
- Elevated uric acid
- Elevated BUN and creatinine
- Elevated lactate dehydrogenase
- Hypoalbuminemia
- Hypoglycemia
Diagnostic Procedures/Other
- Gold standard: Liver biopsy with evidence of microvesicular steatosis. This is rarely used for diagnosis in the clinical setting. Should be avoided in patients with coagulopathies
- Diagnosis is based on symptoms and labs.
- The Swansea criteria is a proposed diagnostic tool by Ch'ng et al (5)[C]. It has a sensitivity of 100%, a specificity of 57%, a positive predictive value of 85%, and a negative predictive value of 100% (3)[C].
- Swansea criteria: presence of 6 out of the 14 criteria in absence of an alternate diagnosis
- Nausea/vomiting
- Severe abdominal pain
- Polydipsia/polyuria
- Encephalopathy
- Elevated bilirubin
- Hypoglycemia
- Elevated uric acid
- Leukocytosis
- Elevated liver enzymes
- Elevated ammonia
- Renal impairment
- Coagulopathy
- Ascites on ultrasound
- Steatosis in hepatocytes on liver biopsy
- 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 (6)[C].
TREATMENT
GENERAL MEASURES
- Continuous maternal and fetal monitoring
- Delivery as soon as possible
- Consider cesarean section if remote from vaginal delivery.
- Serial labs to trend
- Monitor urine output via Foley catheter for most accurate measurements.
- Ensure adequate hydration with IVF as needed.
- Treat coagulopathy with blood products and needed.
- Correct electrolyte and acid-base disturbances.
- Controversy exists regarding induction of labor versus cesarean delivery. Must take into consideration maternal condition, fetal condition, risk of bleeding, how remote from delivery the patient is at diagnosis (6)[C].
- Monitor neonate for features of fatty acid oxidation defects (7)[C].
MEDICATION
Consider broad-spectrum antibiotics for gram-negative bacteria to prevent sepsis (7)[C].
ISSUES FOR REFERRAL
- Patients will likely require intensive care treatment and multidisciplinary approach.
- Liver failure may require transplant or human fetal liver cell transplantation.
INPATIENT CONSIDERATIONS
All treatment will occur as an inpatient.
ONGOING CARE
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.
- 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 deficiency after delivery.
PROGNOSIS
- Maternal mortality rate of 18%
- Death secondary to sepsis, renal failure, cardiac failure, pancreatitis, gastrointestinal bleed
- Fetal mortality rate of 23%
- If the mother and child survive, full clinical recovery usually occurs over several weeks (2)[C].
- Neonatal morbidity risks also stem from prematurity and intrauterine growth restriction.
- Risk in subsequent pregnancies is 25% if the fetus has LCHAD deficiency (4)[C].
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
REFERENCES
11 Kamimura K, Abe H, Kawai H, et al. Advances in understanding and treating liver diseases during pregnancy: a review. World J Gastroenterol. 2015;21(17):5183-5190.22 Ahmed KT, Almashhrawi AA, Rahman RN, et al. Liver diseases in pregnancy: diseases unique to pregnancy. World J Gastroenterol. 2013;19(43):7639-7646.33 Knight M, Nelson-Piercy C, Kurinczuk JJ, et al. A prospective national study of acute fatty liver of pregnancy in the UK. Gut. 2008;57(7):951-956.44 Ko HH, Yoshida E. Acute fatty liver of pregnancy. Can J Gastroenterol. 2006;20(1):25-30.55 Ch'ng CL, Morgan M, Hainsworth I, et al. Prospective study of liver dysfunction in pregnancy in Southwest Wales. Gut. 2002;51(6):876-880.66 Wei Q, Zhang L, Liu X. Clinical diagnosis and treatment of acute fatty liver of pregnancy: a literature review and 11 new cases. J Obstet Gynaecol Res. 2010;36(4):751-756.77 Goel A, Jamwal KD, Ramachandran A, et al. Pregnancy-related liver disorders. J Clin Exp Hepatol. 2014;4(2):151-162.
ADDITIONAL READING
- Nelson DB, Yost NP, Cunningham FG. Acute fatty liver of pregnancy: clinical outcomes and expected duration of recovery. Am J Obstet Gynecol. 2013;209(5):456.e1-456.e7.
- Nelson DB, Yost NP, Cunningham FG. Hemostatic dysfunction with acute fatty liver of pregnancy. Obstet Gynecol. 2014;124(1):40-46.
- Vigil-de Gracia P, Montufar-Rueda C. Acute fatty liver of pregnancy: diagnosis, treatment, and outcome based on 35 consecutive cases. J Matern Fetal Neonatal Med. 2011;24(9):1143-1146.
CODES
ICD10
- K76.0 Fatty (change of) liver, not elsewhere classified
- O26.619 Liver and biliary tract disord in pregnancy, unsp trimester
- 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
ICD9
- 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
necrosis of liver of pregnancy (disorder)
CLINICAL PEARLS
Stabilization of the mother, early recognition, and delivery are the keys for successful management.