Acute Fatty Liver of Pregnancy (AFLP)

Overview

Acute fatty liver of pregnancy (AFLP) is a rare but potentially fatal complication that typically occurs in the third trimester of pregnancy or early postpartum period. This condition is characterized by microvesicular fatty infiltration of the liver, leading to liver failure. Despite its name suggesting a benign fatty change, AFLP is a medical emergency that requires immediate recognition and intervention. The condition affects approximately 1 in 7,000 to 20,000 pregnancies and, if left untreated, can result in significant maternal and fetal mortality.

AFLP is believed to be related to a deficiency in the enzyme long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), which is involved in fatty acid metabolism. When the fetus inherits specific genetic mutations affecting this enzyme, the mother's liver may be unable to process certain fatty acids properly during pregnancy, leading to their accumulation in liver cells. This accumulation causes severe liver dysfunction, coagulopathy, and can progress to multi-organ failure if not treated promptly.

The condition was first described in 1940, and historically carried a very high mortality rate for both mother and baby. However, with increased awareness, earlier recognition, and improvements in critical care, the prognosis has improved significantly. Today, with prompt diagnosis and appropriate management, maternal mortality has decreased to approximately 10-18%, though the condition remains a serious obstetric emergency requiring immediate delivery of the baby and intensive supportive care.

Symptoms

The symptoms of AFLP can be non-specific initially, which may delay diagnosis. The condition typically presents in the third trimester, most commonly between 30-38 weeks of gestation, though it can occur earlier or in the immediate postpartum period.

Early Symptoms

Progressive Symptoms

• Jaundice (yellowing of skin and eyes)
• Dark urine and pale stools
• Headache (may indicate associated preeclampsia)
• Excessive thirst and frequent urination
• Swelling (edema) of legs and face
• Decreased urine output as condition worsens

Severe Symptoms (Medical Emergency)

• Confusion or altered consciousness
• Severe upper abdominal pain
• Signs of bleeding (bruising, bleeding gums, nosebleeds)
• Severe hypoglycemia symptoms (shakiness, sweating)
• Signs of liver failure (encephalopathy)
• Respiratory distress

Associated Conditions

AFLP may occur alongside or be confused with:

• Preeclampsia (present in 20-40% of AFLP cases)
• HELLP syndrome (overlapping features)
• Acute viral hepatitis
• Drug-induced liver injury

Causes

The exact cause of AFLP is not fully understood, but research has identified several factors that contribute to its development.

Genetic Factors

The primary mechanism involves a deficiency in fatty acid oxidation:

• LCHAD deficiency: Mutations in the gene encoding long-chain 3-hydroxyacyl-CoA dehydrogenase
• Fetal inheritance of G1528C or E474Q mutations
• Heterozygous mothers carrying affected fetuses at highest risk
• Accumulation of toxic fatty acid metabolites

Metabolic Disruption

• Impaired mitochondrial fatty acid beta-oxidation
• Accumulation of long-chain fatty acids in maternal liver
• Increased metabolic demands of pregnancy
• Placental production of toxic metabolites

Contributing Factors

• Hormonal changes: High estrogen levels in late pregnancy
• Nutritional factors: Poor nutrition or prolonged fasting
• Oxidative stress: Increased free radical production
• Inflammatory response: Cytokine activation

Pathophysiology

The disease process involves:

• Microvesicular fatty infiltration of hepatocytes
• Mitochondrial dysfunction
• Decreased hepatic function
• Coagulopathy from decreased clotting factor production
• Hypoglycemia from impaired gluconeogenesis
• Potential progression to fulminant hepatic failure

Risk Factors

While AFLP can occur in any pregnancy, certain factors increase the risk:

Pregnancy-Related Factors

• First pregnancy (primiparity)
• Multiple gestation: Twins or higher-order multiples
• Male fetus: Slightly higher incidence
• Previous pregnancy with AFLP: Recurrence risk ~25%
• Preeclampsia: Concurrent condition in many cases

Maternal Factors

• Maternal age (extremes of reproductive age)
• Low body mass index (BMI)
• Nutritional deficiencies
• Previous liver disease
• Genetic predisposition

Genetic Risk Factors

• Carrier status for LCHAD mutations
• Family history of fatty acid oxidation disorders
• Previous child with fatty acid oxidation disorder
• Ethnicity (slightly higher in Caucasians)

Other Associations

• Use of certain medications (aspirin, tetracycline)
• Viral infections during pregnancy
• Metabolic stress
• Prolonged hyperemesis gravidarum

Diagnosis

Early diagnosis of AFLP is crucial but challenging due to non-specific symptoms. A high index of suspicion is needed for any pregnant woman presenting with liver dysfunction in the third trimester.

Clinical Assessment

• Detailed history of symptoms and their progression
• Physical examination for jaundice, tenderness, encephalopathy
• Assessment of fetal well-being
• Evaluation for signs of coagulopathy

Laboratory Tests

Liver Function Tests

• Elevated aminotransferases (AST, ALT) - usually < 1000 U/L
• Elevated bilirubin (conjugated and unconjugated)
• Elevated alkaline phosphatase (beyond normal pregnancy increase)
• Low albumin levels
• Elevated ammonia (indicates liver failure)

Coagulation Studies

• Prolonged prothrombin time (PT) and INR
• Prolonged partial thromboplastin time (PTT)
• Low fibrinogen (< 100 mg/dL is concerning)
• Thrombocytopenia

Other Important Tests

• Hypoglycemia: Often profound and recurrent
• Elevated creatinine: Indicates renal involvement
• Elevated white blood cell count
• Elevated uric acid: Disproportionate to preeclampsia
• Metabolic acidosis: From lactate accumulation

Imaging Studies

• Ultrasound: May show fatty liver (bright liver), ascites
• CT scan: Shows decreased liver attenuation (if safe to perform)
• MRI: Can detect fatty infiltration

Swansea Criteria

Six or more of the following features in the absence of another explanation:

• Vomiting
• Abdominal pain
• Polydipsia/polyuria
• Encephalopathy
• Elevated bilirubin > 14 μmol/L
• Hypoglycemia < 4 mmol/L
• Elevated uric acid > 340 μmol/L
• Leukocytosis > 11 × 10⁹/L
• Ascites or bright liver on ultrasound
• Elevated transaminases
• Elevated ammonia > 47 μmol/L
• Renal impairment (creatinine > 150 μmol/L)
• Coagulopathy (PT > 14 seconds or aPTT > 34 seconds)
• Microvesicular steatosis on liver biopsy

Treatment Options

AFLP is a medical emergency requiring immediate intervention. The definitive treatment is prompt delivery of the baby, regardless of gestational age.

Immediate Management

• Stabilization: IV access, monitoring, ICU admission
• Delivery planning: Urgent multidisciplinary team consultation
• Glucose management: IV dextrose for hypoglycemia
• Coagulopathy correction: Fresh frozen plasma, cryoprecipitate
• Blood pressure management: If concurrent preeclampsia

Delivery Considerations

• Delivery within 24-48 hours of diagnosis is ideal
• Vaginal delivery preferred if maternal condition stable
• Cesarean section for obstetric indications or maternal instability
• Regional anesthesia contraindicated if coagulopathy
• Prepare for potential massive hemorrhage

Supportive Care

Hematologic Support

• Fresh frozen plasma for INR > 1.5
• Platelet transfusion for count < 20,000 or bleeding
• Cryoprecipitate for fibrinogen < 100 mg/dL
• Packed red blood cells for anemia

Metabolic Support

• Continuous glucose monitoring and replacement
• Electrolyte correction
• Lactulose for hepatic encephalopathy
• Protein restriction if encephalopathy present

Renal Support

• Fluid management
• Monitor urine output closely
• Hemodialysis if acute kidney injury develops
• Avoid nephrotoxic medications

Postpartum Care

• Continue ICU monitoring
• Watch for complications (bleeding, infection, organ failure)
• Gradual improvement expected over 1-4 weeks
• Liver transplant rarely needed (< 10% of cases)
• Psychological support for mother and family

Fetal/Neonatal Considerations

• Continuous fetal monitoring until delivery
• Neonatal ICU team presence at delivery
• Screen newborn for LCHAD deficiency
• Monitor for hypoglycemia in newborn
• Long-term follow-up if fatty acid oxidation disorder diagnosed

Prevention

While AFLP cannot always be prevented, certain measures may help reduce risk or enable earlier detection.

Preconception Counseling

• Genetic counseling for women with previous AFLP
• Testing for LCHAD mutations in high-risk families
• Optimization of maternal health before pregnancy
• Discussion of recurrence risks (approximately 25%)

During Pregnancy

• Regular prenatal care with liver function monitoring
• Maintain adequate nutrition, avoid prolonged fasting
• Prompt evaluation of gastrointestinal symptoms in third trimester
• Close monitoring if carrying multiples
• Education about warning signs

High-Risk Management

For women with previous AFLP or known risk factors:

• Serial liver function tests in third trimester
• Regular glucose monitoring
• Fetal testing for well-being
• Delivery planning at tertiary care center
• Multidisciplinary team involvement

Future Pregnancy Planning

• Complete recovery before attempting another pregnancy
• Genetic testing and counseling
• Early pregnancy dating and monitoring
• Consideration of prophylactic measures
• Delivery at facility with appropriate resources

When to See a Doctor

AFLP is a medical emergency. Any concerning symptoms in the third trimester require immediate evaluation.

Seek Emergency Care Immediately

Go to the emergency room or call emergency services for:

• Persistent vomiting with abdominal pain in third trimester
• Yellowing of skin or eyes (jaundice)
• Confusion or altered mental state
• Severe upper abdominal pain
• Signs of bleeding (easy bruising, nosebleeds)
• Severe fatigue with other symptoms
• Dark urine and pale stools
• Excessive thirst and urination with other symptoms

Contact Your Healthcare Provider

Call your obstetrician promptly for:

• Persistent nausea/vomiting in third trimester
• New onset upper abdominal discomfort
• Unusual fatigue or malaise
• Any concerns about your symptoms
• History of AFLP in previous pregnancy

Important Considerations

• Don't dismiss symptoms as "normal" pregnancy discomfort
• AFLP can progress rapidly
• Early diagnosis improves outcomes
• Better to be evaluated unnecessarily than miss diagnosis
• Inform providers of any family history of liver disease

Related Conditions

Frequently Asked Questions