What is the management approach for acute fatty liver of pregnancy (AFLP) complicated by diabetes insipidus (DI)?

Management of Acute Fatty Liver of Pregnancy Complicated by Diabetes Insipidus

The management of acute fatty liver of pregnancy (AFLP) complicated by diabetes insipidus requires expedited delivery after maternal stabilization, followed by supportive care including desmopressin (DDAVP) administration for diabetes insipidus, and consideration for intensive care admission in severe cases.

Diagnosis and Initial Assessment

• AFLP typically presents in the third trimester with symptoms including nausea, vomiting, right upper quadrant or epigastric pain, and jaundice 1
• Diabetes insipidus (DI) may complicate AFLP due to reduced hepatic degradation of placental vasopressinase, leading to increased vasopressinase activity and AVP degradation 2, 3
• Laboratory findings in AFLP include:
  • Elevated transaminases (ALT, AST), lactate dehydrogenase, and direct bilirubin 1
  • Coagulation abnormalities (prolonged PT, low fibrinogen, elevated D-dimer) 1
  • Hypoglycemia is a characteristic finding 4
• The Swansea criteria should be used for diagnosis of AFLP, with ≥6 criteria highly correlating with clinical diagnosis 4, 5

Management Algorithm

Step 1: Maternal Stabilization and Monitoring

• Patients with AFLP who develop encephalopathy, elevated serum lactate (>2.8 mg/dl), MELD score >30, or Swansea criteria >7 should be admitted to intensive care 4
• Correct coagulopathy and metabolic derangements before delivery 4
• Monitor for hypoglycemia, which is common in AFLP 4
• For diabetes insipidus manifestations:
  • Administer desmopressin (DDAVP), which is resistant to degradation by placental vasopressinase 2, 3
  • Oral DDAVP has been used successfully in pregnant patients with DI 2

Step 2: Expedited Delivery

• Delivery should be expedited once coagulopathy and metabolic derangements have been treated 4
• Decisions about mode of delivery should be made jointly by obstetricians, hepatologists, and the multidisciplinary team 4
• Early recognition of AFLP and prompt delivery are critical for achieving good outcomes 4

Step 3: Post-Delivery Management

• Continue close monitoring for complications including:
  • Hypoproteinemia (occurs in 75% of cases) 1
  • Coagulopathy (54%) 1
  • Acute renal failure (39%) 1
• For persistent diabetes insipidus, continue DDAVP treatment, which typically resolves after delivery 2, 3
• Based on limited data from small case series, plasma exchange post-delivery may be considered to improve maternal disease severity and decrease recovery time in severe cases 4
• N-acetylcysteine may be considered in women requiring intensive care admission, although evidence is limited 4

Step 4: Liver Transplantation Consideration

• In the subset of women with AFLP who have severe hepatic impairment, early referral to a transplant center should be made 4
• Postpartum transplantation has occasionally been necessary in severe cases 4

Special Considerations

• Prothrombin time (PT) and INR are risk factors for fatal complications in patients with AFLP 1
• Newborns of mothers with AFLP should be screened for long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, as there is a strong association between AFLP and this fetal metabolic disorder 4
• Diabetes insipidus that first manifests during pregnancy may be associated with abnormal liver function and should be monitored closely 6
• Transient gestational diabetes insipidus typically resolves after delivery but may recur in subsequent pregnancies 3

Monitoring and Follow-up

• Ensure normalization of liver function tests within 3 months post-delivery 7
• If liver function tests remain abnormal, investigate for underlying liver disease 7
• Recovery from AFLP is typically rapid after delivery, with supportive care being the primary treatment 4
• Women with a history of AFLP-associated DI should receive pre-pregnancy counseling before subsequent pregnancies 2