Acute Fatty Liver of Pregnancy (AFLP)
Acute Fatty Liver of Pregnancy (AFLP) is a rare but life-threatening obstetric emergency characterized by microvesicular fatty infiltration of hepatocytes.
Hypoglycemia + jaundice + coagulopathy in third-trimester pregnancy should strongly suggest AFLP.
It typically occurs during the third trimester (30–38 weeks) or in the early postpartum period and requires immediate delivery regardless of gestational age once diagnosed.
Risk factors
|
Maternal Factors |
Fetal Factors |
|
Primigravida |
Male fetus |
|
Multiple gestation |
LCHAD deficiency |
|
Previous AFLP |
Fatty acid oxidation defects |
|
Low BMI |
Twin pregnancy |
Pathophysiology
Defect in fetal fatty acid oxidation → accumulation of toxic fatty acid metabolites → maternal liver injury.
The most important defect:
Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency
Part of:Mitochondrial Trifunctional Protein
Normal Fatty Acid Oxidation
Long-chain fatty acids enter mitochondria.Undergo β-oxidation.
Generate:ATP/Ketones
Critical during pregnancy because maternal metabolism increasingly relies on fatty acid oxidation.
What Happens in AFLP?
Fetus possesses:LCHAD mutation
Placenta generates:Toxic fatty acid intermediates
These enter maternal circulation.
Maternal liver cannot metabolize the excess load.
Result:
- Mitochondrial injury
- Hepatocyte dysfunction
- Microvesicular fat accumulation
Eventually:
- Liver failure
- Coagulopathy
- Hypoglycemia
Histopathology
Microvesicular steatosis
Features:
- Tiny fat droplets
- Hepatocyte swelling
- Minimal inflammation
- Minimal necrosis
Predominantly:Centrilobular
Unlike NAFLD:
|
AFLP |
NAFLD |
|
Microvesicular |
Macrovesicular |
|
Pregnancy-related |
Metabolic syndrome |
|
Acute liver failure |
Chronic disease |
Maternal Physiological Consequences
Liver
- Hepatic failure
- Cholestasis
- Reduced synthetic function
Coagulation
Reduced synthesis of:
- Fibrinogen
- Factors II, V, VII, IX, X
Produces:
- DIC
- Severe bleeding
Glucose Metabolism
Failure of:Gluconeogenesis/Glycogenolysis
Results in:Severe hypoglycemia
Hypoglycemia is one of the most important clues favoring AFLP over HELLP.
Kidney
Acute kidney injury develops in:50–70%
Mechanisms:
- Hepatorenal physiology
- ATN
- Shock
CNS
- Encephalopathy
- Cerebral edema
- Coma
Clinical Features
Usually develops over days.
Prodromal Symptoms
Most common:
- Malaise
- Fatigue
- Anorexia
- Nausea
- Vomiting
Often mistaken for normal pregnancy symptoms.
Progressive Symptoms
- Abdominal pain
- Right upper quadrant pain
- Epigastric pain
- Jaundice
Jaundice occurs in approximately 70%.
Severe Disease
- Altered sensorium
- Encephalopathy
- Bleeding
- Oliguria
- Shock
Physical Examination
May show:
- Jaundice
- Icterus
- Edema
- Ascites
- Hepatomegaly (uncommon)
- Encephalopathy
Swansea Criteria
Diagnosis likely if:Six or more criteria are present without another explanation.
|
Swansea Criterion |
Finding |
|
1 |
Vomiting |
|
2 |
Abdominal pain |
|
3 |
Polydipsia and/or polyuria |
|
4 |
Encephalopathy |
|
5 |
Elevated bilirubin (>14 μmol/L or >0.8 mg/dL), commonly 5–15 mg/dL. |
|
6 |
Hypoglycemia (<4 mmol/L or <70 mg/dL)-most important |
|
7 |
Elevated urate (uric acid) |
|
8 |
Leukocytosis (>11,000/mm³) |
|
9 |
Ascites or bright liver on ultrasound |
|
10 |
Elevated transaminases (AST/ALT) AST: Usually 100–500 IU/L ALT: Usually 100–500 IU/L Rarely >1000 IU/L. This differentiates AFLP from viral hepatitis, where transaminases are often much higher. |
|
11 |
Elevated ammonia (>47 μmol/L) |
|
12 |
Renal impairment (elevated creatinine) |
|
13 |
Coagulopathy (prolonged PT/INR or aPTT) |
|
14 |
Microvesicular steatosis on liver biopsy |
≥6 criteria strongly suggest AFLP.
Sensitivity:≈85–100%
Imaging
|
Imaging Modality |
Findings in AFLP |
|
Ultrasound (USG) |
May show: • Fatty infiltration of the liver • Bright liver (increased echogenicity) • Ascites Sensitivity is poor. A normal ultrasound does NOT exclude AFLP. |
|
Computed Tomography (CT) |
May show: • Diffuse low-attenuation liver consistent with fatty infiltration Rarely required for diagnosis. |
|
Magnetic Resonance Imaging (MRI) |
Most sensitive imaging modality for detecting fatty infiltration. However, it is rarely needed in routine clinical practice because AFLP is usually diagnosed clinically and biochemically. |
Liver Biopsy
Gold standard:Microvesicular steatosis.
However:
Usually avoided because:
- Coagulopathy
- Bleeding risk
Diagnosis is generally clinical.
Differential Diagnosis
AFLP vs HELLP Syndrome
|
Feature |
AFLP |
HELLP |
|
Hypoglycemia |
Common |
Rare |
|
Encephalopathy |
Common |
Rare |
|
Jaundice |
Marked |
Mild |
|
Coagulopathy |
Severe |
Mild |
|
DIC |
Common |
Less common |
|
Platelets |
Mild decrease |
Marked decrease |
|
Hemolysis |
Mild |
Prominent |
|
Liver failure |
Common |
Rare |
AFLP vs Viral Hepatitis
|
Feature |
AFLP |
Viral Hepatitis |
|
Pregnancy |
Yes |
Any |
|
Hypoglycemia |
Common |
Rare |
|
DIC |
Common |
Rare |
|
AST/ALT |
Usually <500 |
Often >1000 |
|
Leukocytosis |
Common |
Less common |
AFLP vs Intrahepatic Cholestasis of Pregnancy
|
Feature |
AFLP |
ICP |
|
Jaundice |
Yes |
Mild |
|
Coagulopathy |
Common |
No |
|
Hypoglycemia |
Yes |
No |
|
Liver failure |
Yes |
No |
|
Pruritus |
Usually absent |
Severe |
Maternal Complications
Hepatic
- Acute liver failure
- Encephalopathy
- Cerebral edema
Hematologic
- DIC
- Massive hemorrhage
Renal
- AKI
- Renal replacement therapy
Respiratory
- ARDS
- Pulmonary edema
Pancreatic
- Acute pancreatitis
Infectious
- Sepsis
Cardiovascular
- Shock
- MODS
Fetal Complications
- Prematurity
- Fetal distress
- Intrauterine death
- Neonatal hypoglycemia
- Neonatal fatty acid oxidation disorders
Management
Immediate Delivery
Once AFLP is suspected:
Prompt delivery is the definitive treatment.
Do not delay for normalization of labs.
Hepatic Encephalopathy
Standard acute liver failure management:
- Airway protection
- ICP precautions
- Ammonia control
DIC Management
Treat underlying AFLP plus:
- Blood products
- Fibrinogen replacement
- Massive transfusion protocols if necessary
Obstetric Management
Preferred:Vaginal delivery if stable and imminent
However:Cesarean frequently required
Decision depends on:
- Maternal status
- Fetal status
- Cervical readiness
Delivery should never be delayed because of coagulopathy alone.
Role of Plasma Exchange
Increasing evidence supports:
Therapeutic Plasma Exchange (TPE)
May improve:
- Bilirubin
- Coagulopathy
- Organ dysfunction
Consider in:
- Persistent liver failure after delivery
- Severe MODS
- Refractory disease
Liver Transplantation
Rarely needed.
Consider when:
- Progressive hepatic failure
- Irreversible liver injury
- Fulminant liver failure after delivery
Only 1–5% require transplant.
Postpartum Course
Typically:Clinical improvement begins within 24–72 hours after delivery.
Laboratory normalization:Days to weeks
Liver usually recovers completely.
Prognosis
Maternal survival:90–95%
Fetal survival:≈80–90%
Early diagnosis and prompt delivery remain the strongest predictors of outcome.