How do you differentiate and manage AFLP (Acute Fatty Liver of Pregnancy), ICP (Intrahepatic Cholestasis of Pregnancy), and hepatitis in pregnancy?

Differentiation Between AFLP, ICP, and Hepatitis in Pregnancy

Prompt diagnosis and management of liver diseases in pregnancy is critical, with AFLP requiring immediate delivery after maternal stabilization due to its high mortality risk, while ICP and hepatitis have different management approaches based on their distinct clinical presentations.

Clinical Features and Timing

Acute Fatty Liver of Pregnancy (AFLP)

• Timing: Typically third trimester or postpartum (rarely earlier) 1
• Frequency: Rare (0.01% of pregnancies) 1
• Clinical presentation:
  • Nausea/vomiting (88.5%), jaundice (71.4%), abdominal pain (51.4%) 2
  • Polydipsia/polyuria, encephalopathy 1
  • Hypoglycemia (94.2%), renal failure (94.2%), coagulopathy (77.1%) 2
• Risk factors: Multiple gestation, male fetus 1
• Association: Linked to fetal LCHAD deficiency 1

Intrahepatic Cholestasis of Pregnancy (ICP)

• Timing: Second and third trimester 1
• Frequency: 0.3-0.5% of pregnancies 1
• Clinical presentation:
  • Pruritus (primary symptom)
  • Jaundice (less common)
  • Normal imaging
• Risk factors: Family history, multiparity, multiple gestation 1

Hepatitis in Pregnancy

• Timing: Can occur at any time during pregnancy
• Clinical presentation:
  • Viral hepatitis: Jaundice, malaise, nausea, right upper quadrant pain
  • Autoimmune hepatitis: May have extrahepatic manifestations
• Risk factors: Exposure history, pre-existing autoimmune conditions

Laboratory Findings

AFLP

• Bilirubin typically <5 mg/dL
• ALT/AST moderately elevated (<500 U/L)
• Prolonged prothrombin time
• Hypoglycemia (characteristic)
• Elevated creatinine
• Elevated ammonia
• DIC in >75% of cases 1

ICP

• Elevated bile acids (key diagnostic feature)
• Bilirubin typically <5 mg/dL
• Mild to moderate elevation of transaminases
• Normal coagulation studies initially

Hepatitis

• Markedly elevated transaminases (often >1000 U/L in viral hepatitis)
• Variable bilirubin elevation
• Positive viral markers (HBsAg, anti-HCV) or autoimmune markers
• Coagulopathy in severe cases

Imaging Findings

AFLP

• Ultrasound may show fatty infiltration
• Sometimes ascites 1

ICP

• Normal imaging 1

Hepatitis

• Normal or hepatomegaly
• May show heterogeneous echotexture in viral hepatitis

Diagnostic Criteria

AFLP

• Swansea criteria: Requires 6 or more of the following:
  • Vomiting
  • Abdominal pain
  • Polydipsia/polyuria
  • Encephalopathy
  • Elevated transaminases
  • Elevated bilirubin
  • Hypoglycemia
  • Elevated uric acid
  • Leukocytosis
  • Ascites or bright liver on ultrasound
  • Elevated ammonia
  • Renal impairment
  • Coagulopathy
  • Microvesicular steatosis on liver biopsy 1

ICP

• Pruritus (typically without rash)
• Elevated serum bile acids (>10 μmol/L)
• No other cause of liver disease

Hepatitis

• Viral: Positive serologic markers
• Autoimmune: Positive autoantibodies, elevated IgG, compatible histology

Management

AFLP

• Immediate delivery after maternal stabilization regardless of gestational age 1, 3
• Intensive supportive care:
  • Correction of hypoglycemia
  • Management of coagulopathy
  • Monitoring for renal failure
• Consider transfer to liver transplant center if signs of liver failure persist 4
• Liver transplantation evaluation for patients who progress to acute liver failure 1

ICP

• Ursodeoxycholic acid (10-15 mg/kg/day) 1
• Delivery timing based on bile acid levels:

  • 100 μmol/L: Delivery at 35-36 weeks

  • <100 μmol/L: Delivery at 37-39 weeks 1

Hepatitis

• Viral hepatitis: Supportive care, specific antivirals for certain types
  • For HBV: Continue tenofovir throughout pregnancy if already on treatment 1
  • For HCV: Treatment typically deferred until after delivery 1
• Autoimmune hepatitis: Continue immunosuppression at lowest effective dose 1
  • Corticosteroids (prednisone 40-60 mg/day) if acute presentation 1

Maternal and Fetal Outcomes

AFLP

• Maternal mortality: 7-18% 1
• Fetal mortality: 9-23% 1
• Complications: Acute renal failure, encephalopathy, DIC

ICP

• Maternal: Generally good, recurrence in subsequent pregnancies (45-70%) 1
• Fetal: Risk of stillbirth (0.4-1%), especially with bile acids >100 μmol/L 1

Hepatitis

• Variable depending on etiology and severity
• Viral hepatitis: Generally good maternal outcome except for hepatitis E in endemic areas
• Autoimmune hepatitis: Risk of flare (30%) during pregnancy or postpartum

Key Distinguishing Features

1. Hypoglycemia: Characteristic of AFLP, not typically seen in ICP or hepatitis
2. Pruritus: Primary symptom in ICP, less common in AFLP or hepatitis
3. Bile acids: Markedly elevated in ICP, may be elevated in AFLP
4. Renal involvement: Common in AFLP, uncommon in ICP or early hepatitis
5. Coagulopathy: Severe in AFLP, mild or absent in early ICP, variable in hepatitis
6. Encephalopathy: Common in AFLP, rare in ICP, late finding in severe hepatitis

Pitfalls to Avoid

1. Delayed diagnosis of AFLP: Can rapidly progress to liver failure; requires high index of suspicion
2. Misdiagnosis of AFLP as viral hepatitis: Can lead to delayed delivery and worse outcomes
3. Relying solely on transaminase levels: May be only moderately elevated in AFLP despite severe disease
4. Overlooking hypoglycemia: A key diagnostic clue for AFLP
5. Waiting for liver biopsy: Treatment decisions for AFLP should not be delayed for histologic confirmation

Remember that AFLP can coexist with preeclampsia in approximately 50% of cases, which may complicate the clinical picture 1. The presence of the "AFLP-Triad" (symptoms: nausea/vomiting, jaundice, epigastric pain; laboratory: renal dysfunction, coagulopathy, liver function abnormalities, hypoglycemia; complications: renal failure, coagulopathy, ascites, encephalopathy) should prompt immediate evaluation for AFLP 2.