Pregnancy-associated liver diseases

Acute Fatty Liver of Pregnancy (AFLP)

Epidemiology & Risk Factors

• Rare, life-threatening maternal condition occurring typically in the 3rd trimester (>30 weeks GA) or early postpartum.
• Etiology: Defect in fetal fatty acid mitochondrial beta-oxidation.
  • Fetus has long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency (autosomal recessive).
  • Mother is heterozygous. Accumulation of toxic fetal/placental fatty acid metabolites in maternal liver leads to microvesicular steatosis.
• Risk Factors:
  • Primiparity
  • Multiple gestations (twins/triplets)
  • Male fetus
  • Previous history of AFLP

Clinical Features

• Prodrome: Malaise, fatigue, anorexia, headache, progressive nausea & vomiting (N/V).
• Maternal Liver Dysfunction:
  • Right upper quadrant (RUQ) or epigastric pain
  • Jaundice
  • Encephalopathy (due to hyperammonemia)
• Associated Features:
  • Polyuria/polydipsia (transient nephrogenic diabetes insipidus due to placental vasopressinase clearing maternal ADH faster; AFLP-associated renal injury impairs liver’s ability to clear vasopressinase).
  • Hypertension and proteinuria in up to 20-40% of cases (overlap with preeclampsia).

Diagnosis

• Initial Test & Key Labs:
  • Marked hypoglycemia (<72 mg/dL) due to impaired hepatic glycogenolysis (distinguishing feature). c
  • Prolonged PT/INR and aPTT (due to acute hepatic synthesis failure, consumption). c
  • Elevated transaminases (AST & ALT), typically elevated but usually <1000 U/L.
  • Leukocytosis (>11,000/µL).
  • Hyperbilirubinemia, elevated uric acid, hyperammonemia.
  • Acute kidney injury (↑ BUN, ↑ Creatinine).
  • Thrombocytopenia and decreased fibrinogen.
• Imaging:
  • RUQ Ultrasound/CT: May show a “bright liver” (fatty infiltration) or ascites, but possesses poor sensitivity/specificity; mainly used to rule out hepatic hematoma or rupture.
• Confirmatory/Gold Standard:
  • Liver biopsy: Shows pericentral microvesicular steatosis without inflammation or necrosis.
  • Note: Rarely performed due to severe risk of hemorrhage from coagulopathy.
• Clinical Diagnosis:
  • Diagnosed using Swansea Criteria (presence of ≥ 6 clinical, biochemical, or imaging findings in the absence of other liver diseases).

Differential Diagnostics

• HELLP Syndrome:
  • Diff: Hemolysis (schistocytes, ↑ LDH, ↓ haptoglobin), marked thrombocytopenia, and HTN with normal coagulation profile (PT/INR is typically normal in HELLP but prolonged in AFLP). Hypoglycemia is rare in HELLP.
• Intrahepatic Cholestasis of Pregnancy (ICP):
  • Diff: Intense pruritus (worse on palms/soles) and elevated total bile acids without liver failure, coagulopathy, encephalopathy, or hypoglycemia.
• Acute Viral or Acetaminophen Hepatitis:
  • Diff: AST/ALT usually extremely high (>1000-5000 U/L). Diagnosed by positive viral serologies or toxic APAP level. Coagulopathy occurs only in fulminant cases, and there is no specific association with 3rd-trimester gestations.

Management

1. Immediate Stabilization & Intensive Care:
   • Airway, breathing, circulation (ABCs) and continuous fetal monitoring.
   • Aggressively correct hypoglycemia with continuous IV dextrose infusion (e.g., D10 or D50).
   • Correct coagulopathy with fresh frozen plasma (FFP), cryoprecipitate, or platelets before proceeding to delivery to prevent hemorrhage.
2. Definitive Management (Next Best Step):
   • Immediate delivery regardless of gestational age.
   • Rapid vaginal delivery is preferred if stable and induction is progressing; urgent Cesarean section (C-section) for maternal/fetal deterioration or failure to progress.
3. Refractory/Advanced Care:
   • If progressive liver failure, encephalopathy, or severe lactic acidosis persists post-delivery, evaluate for liver transplantation.
   • Desmopressin for transient diabetes insipidus.

Complications

• Hepatic encephalopathy and fulminant acute liver failure.
• Disseminated intravascular coagulation (DIC) and massive postpartum hemorrhage (PPH).
• Acute kidney injury (AKI) / Hepatorenal syndrome.
• Pancreatitis.
• Maternal or fetal death.