CLINICAL ACTIONS:

Acute fatty liver of pregnancy (AFLP) is an uncommon but potentially fatal disease which is unique to pregnancy. The exact pathogenesis of AFLP has yet to be determined. There is no universal standardized approach to diagnosis. Characteristic laboratory findings, imaging and findings may be used for diagnosis when clinical suspicion is present. Liver biopsy is not needed for diagnosis but may be used to decide on early delivery if diagnosis is unclear.

Diagnostic Algorithm When Transaminases are Elevated at > 20 weeks GA

Rule out other potential causes such as the following

• Viral or autoimmune hepatitis
• Alcohol related
• Medications that may cause elevated transaminases or liver injury (e.g., acetaminophen,  allopurinol, omeprazole etc.)
  • Consider herbal preparations such as kava kava (Piper methysticum) and germander (Teucrium chamaedrys)
• Gallstones
• Budd-Chiari syndrome (occlusion of hepatic veins, e.g. blood clot)

Review clinical symptoms and signs

• Abdominal pain, nausea & vomiting
  • May be seen in AFLP but also in other hepatic disorders in pregnancy such as HELLP
• Hypertension
  • Key feature of HELLP/preeclampsia  (see ‘Related ObG Project Topics’ below)
• Polydipsia/polyuria, anorexia, lethargy/encephalopathy
  • May be seen in AFLP
  • Not typical of HELLP or preeclampsia
• Pruritis or jaundice
  • More typical of intrahepatic cholestasis of pregnancy (ICP)

Lab/Imaging

• Biochemistry
  • Hypoglycemia
    • Seen in AFLP but not typical of HELLP/Preeclampsia or ICP
  • AST and ALT usually <1000
    • Elevated 5 to 10x in ALFP, 1-100x in HELLP/preeclampsia and 1-5x in ICP
  • Elevated serum ammonia | uric acid | hyperbilirubinemia | BUN & Cr
• Coag studies
  • Prolonged PT/PTT/INR and decreased fibrinogen
• Hematology
  • Elevated WBC with normal hematocrit
    • Leucocytosis more common in AFLP
    • Thrombocytopenia more likely in HELLP
• Liver biopsy (gold standard)
  • Characterized by microvesicular fatty infiltration of hepatocytes without inflammation or necrosis
• Ultrasound findings
  • Described as a “bright” liver and ascites may be present

Management

• If AFLP diagnosed, deliver promptly and provide supportive care
  • There can be rapid progression to acute liver failure marked by complications such as coagulopathy, hypovolemia and renal failure
• Patients often requires ICU admission after delivery
• The use of liver transplantation has been reported for cases of worsening clinical status such as encephalopathy, lactic acidosis and persistent renal failure despite maximal medical therapy

SYNOPSIS:

Acute fatty liver of pregnancy is an obstetric emergency which generally manifests after 30 weeks of gestation. The incidence of AFLP is 1:7000-1:15,000 pregnancies and is much lower than that of preeclampsia and HELLP syndrome. Patients may present with nonspecific symptoms such as nausea and vomiting, abdominal pain, jaundice, polydypsia, polyuria and signs of encephalopathy. The Sawnsea Diagnostic Criteria are presented below, but predictive value may be of limited value if other liver disease in pregnancy (e.g., HELLP) is present.

KEY POINTS:

Risk Factors

• Multiple gestation (14x risk in twins)
• Male sex of fetus (3:1 ratio)
• Coexisting diagnosis of liver disease in pregnancy (HELLP, preeclampsia)
• Previous episode of AFLP
• Underlying cause of AFLP is unclear, but an association with mothers and fetuses with mutations in the fatty oxidation pathway has been identified
  • Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is one example of a fetal fatty acid oxidation defect (FAOD)
  • Pregnancy may stress the placenta sufficiently to result in AFLP

Swansea Criteria

AFLP diagnosis if ≥ 6 criteria are present and no other liver disease of pregnancy (e.g., HELLP) is present

• Vomiting [60% of patients with AFLP have this abnormality]
• Abdominal pain [56%]
• Polydipsia/polyuria [12%]
• Encephalopathy [9%]
• Elevated total bilirubin [100%]
  • >0.8 mg/dl (>140 µmol/L)
• Hypoglycemia [78%]
  • <72 mg/dl (4.0 mmol/L)
• Elevated uric acid [88%]
  • >5.7 mg/dl (>340 μmol/L)
• Leucocytosis [98%]
  • >11×10⁹/l
• Elevated ALT/AST [100%]
  • >42 U/l
• Elevated Ammonia [50%]
  • >66 µg/dL (>47 µmol/L)
• Elevated Cr [58%]
  • >1.7 mg/dl (150 µmol/L)
• Coagulopathy [>50%]
  • PT >14s or APTT >34s
  • Plt count >100×10¹² 
• Bright liver on ultrasound [25% ‘bright’ liver or ascites on imaging]
• Ascites
• Microvesicular steatosis on liver biopsy

Treatment Notes

• Treatment of choice is emergent delivery and supportive care
• Maternal liver recovers quickly after delivery with adequate supportive care
• Maternal mortality has dropped from 85% in 1980s to <10%
• Patients are at high risk for DIC and severe postpartum hemorrhage
• Aggressively manage coagulopathies and hypoglycemia

Learn More – Primary Sources:

The American Journal Of Gastroenterology Volume 112 June 2017 Acute Fatty Liver Disease of Pregnancy: Updates in pathogenesis, diagnosis and management

Acute Fatty Liver of Pregnancy: Pathophysiology, Anesthetic Implications, and Obstetrical Management

HELLP Syndrome or Acute Fatty Liver of Pregnancy: A Differential Diagnostic Challenge

Noninvasive Swansea criteria are valuable alternatives for diagnosing acute fatty liver of pregnancy in a Chinese population

Related ObG Topics:

Diagnosing Preeclampsia – Key Definitions and ACOG Guidelines

Gestational Thrombocytopenia – a Diagnosis of Exclusion

ACOG Guidance: Emergency Treatment for Severe Hypertension in Pregnancy

SMFM Recommendations: Intrahepatic Cholestasis of Pregnancy