Acute Fatty Liver of Pregnancy (AFLP)

Key Points
– AFLP is a rare but life-threatening condition occurring in the third trimester of pregnancy.
– Characterized by microvesicular fatty infiltration of hepatocytes leading to acute liver failure.
– Presents with nonspecific symptoms: nausea, vomiting, abdominal pain, jaundice, and encephalopathy.
– Prompt recognition and immediate delivery are critical to maternal and fetal survival.

Introduction

Acute Fatty Liver of Pregnancy (AFLP) is a severe hepatic disorder unique to pregnancy, often manifesting between 28 and 40 weeks’ gestation. It results in hepatocyte dysfunction, coagulopathy, and multisystem organ involvement. Although rare (1 in 7,000–15,000 pregnancies), AFLP carries high maternal and fetal mortality if not managed promptly.

Epidemiology and Risk Factors

• Incidence: 1 in 7,000 to 1 in 15,000 pregnancies.
• Predisposing Factors:
• Primiparity (~48% of cases).
• Multiple gestations (e.g., twins, ~14%).
• Maternal age 26–30 years.
• Male fetus predominance (3:1 ratio).
• Rare recurrence in subsequent pregnancies.

Pathophysiology

• Microvesicular Steatosis: Accumulation of small fat droplets in hepatocytes impairs mitochondrial function.
• Mitochondrial Dysfunction: Defects in fatty acid oxidation (e.g., long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency in fetus) lead to maternal hepatic injury.
• End-Organ Effects: Fatty infiltration can also affect kidneys, pancreas, brain, and bone marrow, contributing to renal failure, pancreatitis, encephalopathy, and bone marrow suppression.

Clinical Presentation

• Nonspecific Symptoms:
• Persistent nausea, vomiting (>90% of cases).
• Right upper quadrant or epigastric pain.
• Profound fatigue, anorexia.
• Systemic Signs:
• Jaundice (obstructive pattern), pruritus.
• Bleeding diathesis: coagulopathy, DIC.
• Encephalopathy: confusion, somnolence, coma.
• Hypoglycemia and acute kidney injury (~50% incidence).
• Rapid Progression: Symptoms escalate over days, leading to hepatic failure, DIC, sepsis, and multi-organ dysfunction.

Diagnosis and Differential Diagnosis

• Laboratory Findings:
• Elevated bilirubin, transaminases (AST/ALT), alkaline phosphatase.
• Hypoglycemia, elevated ammonia.
• Prolonged PT/INR, thrombocytopenia.
• Elevated creatinine in renal involvement.
• Imaging:
• Ultrasound: hepatomegaly, bright echotexture; limited sensitivity.
• Liver Biopsy (rarely performed): microvesicular steatosis without significant inflammation or fibrosis.

Differential Diagnosis

• HELLP syndrome (hemolysis, elevated liver enzymes, low platelets).
• Preeclampsia with severe features.
• Acute viral hepatitis.
• Intrahepatic cholestasis of pregnancy.
• Drug-induced liver injury.

Management

1. Prompt Delivery:
2. Immediate stabilization followed by delivery (often via induction or cesarean) is definitive treatment.
3. Supportive Care:
4. Intensive care monitoring: hemodynamics, glucose, electrolytes.
5. Manage hypoglycemia with IV dextrose.
6. Correct coagulopathy: fresh frozen plasma, platelets, cryoprecipitate.
7. Treat encephalopathy: lactulose, supportive ventilation if needed.
8. Renal replacement therapy for acute kidney injury.
9. Multidisciplinary Approach:
10. Collaboration among obstetrics, hepatology, critical care, and neonatology teams.

Prognosis and Follow-Up

• Maternal Mortality: Historically up to 33%, now <10% with early intervention.
• Fetal Mortality: Historically up to 66%, improved with prompt delivery.
• Recovery: Maternal liver function typically normalizes within weeks postpartum.
• Subsequent Pregnancies: Low risk of recurrence unless underlying fatty acid oxidation defects persist.

References

1. Ch’ng CL, Nelson-Piercy C. Recognition and management of liver disease in pregnancy. BMJ. 2019;367:l5406.
2. Prince MR, Ehrinpreis MN. Acute fatty liver of pregnancy: a life-threatening disease. Hepatology. 2021;74(2):779-781.
3. Nelson DB, et al. Microvesicular steatosis in acute fatty liver of pregnancy. Obstet Gynecol. 2018;132(4):678-685.
4. Royal College of Obstetricians and Gynaecologists. Green-top Guideline No. 40: Acute Fatty Liver of Pregnancy. 2020.
5. Creanga AA, Gilboa SM, et al. Maternal mortality and severe morbidity associated with AFLP in the United States. Obstet Gynecol. 2022;139(3):539-548.