Acute Fatty Liver of Pregnancy

Basics

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].

Diagnosis

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].

Treatment

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].

Inpatient Considerations

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

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.
  • 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

Additional Reading

  • Ahmed KT, Almashhrawi AA, Rahman RN, et al. Liver diseases in pregnancy: diseases unique to pregnancy. World J Gastroenterol. 2013;19(43):7639–7646. [PMID:24282353]
  • 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. [PMID:25954092]
  • 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. [PMID:23860212]
  • Nelson DB, Yost NP, Cunningham FG. Hemostatic dysfunction with acute fatty liver of pregnancy. Obstet Gynecol. 2014;124(1):40–46. [PMID:24901264]
  • 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. [PMID:21668324]

Codes

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)

Clinical Pearls

  • AFLP should be considered with any transaminitis after the 20th week of pregnancy and in women with new onset vomiting and abdominal pain in the 3rd trimester.
  • AFLP is an obstetrical emergency characterized by acute liver failure. Early recognition, prompt delivery, and supportive treatment for the mother and child are the keys for successful management.

Authors


Cecilia M. Kipnis, MD, FAAFP
Matthew Feist, MD

Bibliography

  1. Liu J, Ghaziani TT, Wolf JL. Acute fatty liver disease of pregnancy: updates in pathogenesis, diagnosis, and management. Am J Gastroenterol. 2017;112(6):838–846.  [PMID:25954092]
  2. Ko HH, Yoshida E. Acute fatty liver of pregnancy. Can J Gastroenterol. 2006;20(1):25–30.  [PMID:24282353]
  3. 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.  [PMID:18332072]
  4. 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.  [PMID:16432556]
  5. Goel A, Jamwal KD, Ramachandran A, et al. Pregnancy-related liver disorders. J Clin Exp Hepatol. 2014;4(2):151–162.  [PMID:12427793]


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TY - ELEC T1 - Acute Fatty Liver of Pregnancy ID - 816804 Y1 - 2019 PB - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816804/all/Acute_Fatty_Liver_of_Pregnancy ER -