Acute fatty liver of pregnancy (Swansea criteria) (also searched with possessive/alternate eponym spelling where applicable, ICD-10: O90.4) is a rare, life-threatening obstetric emergency unique to the third trimester of gestation, characterized by widespread maternal hepatic microvesicular steatosis leading to acute liver failure 1,2. Triggered fundamentally by inherited defects in fetal mitochondrial fatty acid oxidation—most notably long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency—the condition presents diagnostic challenges due to overlapping features with severe preeclampsia and HELLP syndrome 3,4. The syndrome is definitively diagnosed utilizing the Swansea criteria (requiring six or more of fourteen specific clinical, laboratory, and histological findings) and demands immediate obstetric delivery combined with intensive multidisciplinary critical care support to prevent maternal and fetal mortality 2,6.

Etiology & Risk Factors

  • Fetal Mitochondrial Enzyme Deficiencies: Maternal heterozygous or homozygous inheritance of mutations in the trifunctional protein subunit alpha (HADHA) gene, particularly the G1528C mutation causing long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency 3,4.
  • Nulliparous and Multiple Gestations: Increased incidence observed in primigravid women and pregnancies carrying male fetuses or multiple gestations (twins/triplets), which amplify metabolic demands on hepatic beta-oxidation pathways 1,2.
  • Genetic Predisposition: Impaired maternal-fetal metabolic interaction where toxic 3-hydroxy fatty acid intermediates cross the placenta and accumulate within the maternal hepatic circulation, inducing direct mitochondrial toxicity 3,4.
  • Prior History of AFLP: Women with a prior pregnancy complicated by AFLP or LCHAD deficiency carry a markedly elevated risk of recurrence in subsequent pregnancies 2.

Pathophysiology

The core pathogenetic mechanism underlying acute fatty liver of pregnancy originates in the metabolic interface between mother and fetus 3,4. When a fetus inherits a fatty acid oxidation defect (such as LCHAD deficiency), the placental transfer of intermediate-chain and long-chain 3-hydroxy fatty acids back into the maternal circulation is severely impaired 3. These unmetabolized fatty acids accumulate in maternal serum and act as direct mitochondrial toxins within hepatocytes 3. The resulting mitochondrial dysfunction severely inhibits hepatic beta-oxidation and the tricarboxylic acid (TCA) cycle, halting adenosine triphosphate (ATP) synthesis and causing profound intracellular energy depletion 3. Consequently, neutral fats accumulate rapidly within hepatocytes as microvesicular steatosis without significant hepatocellular necrosis 1. This massive lipid engorgement causes hepatocyte ballooning, sinusoidal compression, intrahepatic cholestasis, and a catastrophic decline in synthetic liver function, culminating in acute liver failure, coagulopathy, severe hypoglycemia, renal hypoperfusion, and multi-organ system dysfunction 2,5.

Acute fatty liver of pregnancy (Swansea criteria) — Pathophysiological Cascade & Clinical Flowchart 1 Fetal-Maternal Mutation Fetuses carrying homozygous or compound heterozygous long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency place metabolic stress on the mother. 2 Defective Mitochondrial β-Oxidation Accumulation of toxic maternal-fetal 3-hydroxy fatty acid metabolites overwhelms hepatic mitochondrial oxidative capacity. 3 Microvesicular Steatosis Hepatocytes accumulate microvesicular neutral fat without necrosis, leading to rapid intracellular swelling and acute liver failure. 4 Multi-Organ System Collapse Rapid onset of coagulopathy, acute kidney injury, encephalopathy, and profound hypoglycemia. 5 Emergency Delivery & Resuscitation Immediate termination of pregnancy and intensive ICU support arrest disease progression and restore maternal hepatic function.

Clinical Presentation & Classic Clinical Signs

  • History & Cardinal Symptoms: Patients typically present in the 30th to 38th week of gestation with a multi-week prodrome of persistent nausea, intractable vomiting, severe malaise, anorexia, and central epigastric or right upper quadrant abdominal pain 2,6. As hepatic synthetic failure and encephalopathy advance, patients develop progressive jaundice, altered mental status, confusion, and asterixis 2,6.
  • Physical Examination & Named Clinical Signs: Physical examination frequently reveals icteric sclerae and skin, tender hepatomegaly (though the liver may occasionally decrease in size as necrosis/atrophy advances), peripheral edema, and widespread petechiae or ecchymoses secondary to consumptive coagulopathy 2,6. Maternal tachycardia (>100 beats/min) and tachypnea are universal early compensatory signs of systemic inflammatory response and metabolic acidosis 6.

Diagnostic Workup & Interpretation (Laboratory, Imaging & ECG/Pathology)

Diagnostic Modality / Test Expected Clinical & Radiological / Laboratory Finding
Gold-Standard InvestigationSwansea diagnostic criteria (≥6 positive parameters) in conjunction with clinical exclusion of alternative hepatopathies; liver biopsy (rarely required due to coagulopathy) demonstrates microvesicular steatosis with central sparing.
Laboratory PanelMarked leukocytosis (WBC > 15–20 × 109/L), elevated serum transaminases (AST/ALT typically 300–500 IU/L, lower than viral hepatitis), hyperbilirubinemia (total bilirubin > 5 mg/dL), elevated serum creatinine (> 1.2 mg/dL) and uric acid, profound hypoglycemia (blood glucose < 60 mg/dL), and marked coagulopathy (prolonged PT/aPTT, low fibrinogen, elevated D-dimer).
Imaging / Radiology (X-ray, US, CT, MRI)Abdominal ultrasound often demonstrates diffuse hyperechogenicity ("bright liver") due to microvesicular fat infiltration, though normal imaging does not rule out AFLP. Computed tomography and MRI confirm diffuse hepatic steatosis but are generally avoided during pregnancy due to radiation or limited clinical utility.
ECG / Histopathology / ProceduralElectrocardiogram assesses for electrolyte shifts (hyperkalemia, hypocalcemia) secondary to acute kidney injury. Histopathology reveals panacinar microvesicular steatosis with minimal inflammation or necrosis; Oil Red O staining on frozen sections highlights intracellular neutral lipid droplets.

Staging, Classification & Clinical Scoring Systems

Criterion / Stage / Score Component Clinical Threshold, Points & Management Implication
Swansea Diagnostic Criteria (Presence of ≥6 of the following features)1. Vomiting (Present); 2. Abdominal pain (Present); 3. Polydipsia or polyuria (>3 L/day); 4. Encephalopathy (Grade 1–4); 5. Elevated bilirubin (>14 µmol/L or >0.8 mg/dL); 6. Hypoglycemia (<4.0 mmol/L or <72 mg/dL); 7. Elevated blood urea nitrogen (>10 mmol/L or >28 mg/dL); 8. Leukocytosis (>11 × 109/L); 9. Ascites or bright liver on ultrasound; 10. Elevated transaminases (AST/ALT > 42 IU/L); 11. Elevated plasma uric acid (>340 µmol/L or >5.7 mg/dL); 12. Coagulopathy (PT > 14 s or INR > 1.5); 13. Microvesicular steatosis on liver biopsy. Clinical implication: Reaching ≥6 criteria mandates immediate delivery and ICU admission.

Differential Diagnosis

Differential Condition Distinguishing Clinical, Biochemical & Imaging Features
Severe Preeclampsia & HELLP SyndromeMarked hypertension and proteinuria are prominent in preeclampsia; transaminases can be extremely high in HELLP, but profound hypoglycemia, severe coagulopathy with low fibrinogen, and marked encephalopathy strongly favor AFLP.
Acute Viral Hepatitis (A, B, C, E)Marked transaminase elevation (AST/ALT frequently > 1000–3000 IU/L), absence of profound hypoglycemia or early renal failure, and positive specific viral serologies (e.g., IgM anti-HAV, HBsAg, anti-HEV).
Intrahepatic Cholestasis of Pregnancy (ICP)Pruritus is the primary symptom; transaminases are mildly elevated, but synthetic liver function (PT/INR, albumin, glucose) and bilirubin remain largely normal without coagulopathy or renal failure.
Thrombotic Microangiopathies (TTP / HUS)Characterized by severe Coombs-negative hemolytic anemia, profound thrombocytopenia, and fluctuating neurological symptoms, with schistocytes present on peripheral blood smear and normal or mildly elevated liver enzymes.

Management & Treatment Protocol

  • Initial Stabilization & Resuscitation: Immediate admission to the intensive care unit (ICU) with continuous maternal hemodynamic and fetal monitoring 2,6. Establish large-bore IV access, administer continuous intravenous 10% dextrose infusions to correct profound hypoglycemia, and insert an indwelling urinary catheter to monitor strict hourly urine output 2,6.
  • First-Line Medical / Pharmacological Therapy (with exact adult dosing): Aggressive correction of coagulopathy using fresh frozen plasma (FFP at 15–20 mL/kg), cryoprecipitate (if fibrinogen < 100 mg/dL), and platelet transfusions (maintaining platelets > 50,000/µL) prior to delivery 2,7. Administer broad-spectrum intravenous antibiotic coverage (e.g., cefazolin 2 g IV every 8 hours or piperacillin-tazobactam 3.375 g IV every 6 hours) if sepsis or chorioamnionitis is suspected 7. Provide aggressive supportive care for acute kidney injury and hepatic encephalopathy (lactulose 20–30 mL orally or via nasogastric tube every 6–8 hours titrated to 2–3 soft stools daily) 2,7.
  • Surgical / Interventional Indications: Prompt termination of pregnancy regardless of gestational age 2,6. If the cervix is unfavorable or immediate delivery is mandated by maternal deterioration, proceed urgently with low transverse cesarean section under appropriate anesthetic guidance (general anesthesia or invasive arterial monitoring-backed regional anesthesia depending on coagulopathy status) 5,7. Post-delivery, intensive supportive care must continue for 24–72 hours, as liver function often transiently worsens before stabilizing 2,6. In cases of fulminant hepatic failure unresponsive to supportive measures, emergency liver transplantation evaluation is indicated 2.

Complications & Prognosis

  • Maternal Complications: Postpartum hemorrhage, disseminated intravascular coagulation (DIC), acute kidney injury requiring temporary hemodialysis, hepatic encephalopathy, acute respiratory distress syndrome (ARDS), systemic infections/sepsis, and multi-organ failure 2,3,6.
  • Fetal and Neonatal Complications: Fetal distress, intrauterine demise, prematurity-related morbidities, and neonatal hypoglycemia or metabolic decompensation secondary to underlying inherited fatty acid oxidation defects (LCHAD deficiency) 3,4.
  • Prognosis: With early recognition, immediate delivery, and modern multidisciplinary ICU management, maternal mortality has declined from near 85% historically to less than 10%, though perinatal mortality remains significant (7–23%) 2,6. Survivors typically experience complete hepatic recovery without chronic liver disease or cirrhosis 2.