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 (DI) requires prompt maternal stabilization, correction of metabolic derangements and coagulopathy, followed by expedited delivery, with oral desmopressin (DDAVP) as the treatment of choice for DI symptoms. 1, 2

Diagnosis and Initial Assessment

• AFLP diagnosis should be established using the Swansea criteria, with ≥6 criteria highly correlating with clinical diagnosis 1
• Initial symptoms of AFLP may vary considerably, with nausea and vomiting being the most common presenting complaints (23% of cases) 3
• Laboratory evaluation should include:
  • Liver function tests (elevated transaminases, direct bilirubin, lactic dehydrogenase) 1, 3
  • Coagulation profile (abnormal fibrinogen, D-dimer, fibrin degradation products) 3
  • Serum bile acids, alkaline phosphatase, GGT, and platelets 4
• DI in AFLP results from reduced hepatic degradation of placental vasopressinase, leading to increased vasopressin breakdown and subsequent polyuria and polydipsia 5, 2

Management Algorithm

Step 1: Maternal Stabilization and Intensive Monitoring

• Admit patients with AFLP who develop encephalopathy, elevated serum lactate, MELD score >30, or Swansea criteria >7 to intensive care 1
• Monitor for and aggressively treat hypoglycemia, which is a characteristic finding in AFLP 1, 3
• Correct coagulopathy before proceeding to delivery, as prothrombin time (PT) is a significant risk factor for fatal complications (OR = 1.558) 1, 3
• Address hypoproteinemia, coagulopathy, and acute renal failure, which are the main maternal complications of AFLP (75%, 54%, and 39% respectively) 3

Step 2: Management of Diabetes Insipidus

• Administer oral desmopressin (DDAVP) for symptomatic DI, which is resistant to degradation by placental vasopressinase 5, 2
• Monitor fluid balance carefully, as both over and under-correction can lead to complications 6, 2
• Note that DI first recognized during pregnancy may be associated with abnormal liver function and should raise suspicion for AFLP or preeclampsia 6

Step 3: Expedited Delivery

• Proceed with delivery once coagulopathy and metabolic derangements have been treated 1, 4
• The mode of delivery should be determined by a multidisciplinary team including obstetricians and hepatologists 1
• Early recognition of AFLP and prompt delivery are critical for improving maternal and fetal outcomes 1, 3
• Be aware that perinatal mortality is linked to gestational age at delivery and levels of fibrin degradation products 3

Step 4: Post-Delivery Management

• Consider plasma exchange in severe cases to improve maternal disease severity and decrease recovery time 1
• N-acetylcysteine may be considered in women requiring intensive care admission, although evidence is limited 1
• Monitor for resolution of DI symptoms, which typically subside after delivery as this is usually a transient condition 5, 2
• Screen newborns for long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency due to its strong association with AFLP 1

Follow-up and Monitoring

• Ensure normalization of liver function tests within 3 months post-delivery 1, 4
• If liver function tests remain abnormal, investigate for underlying liver disease 1, 4
• Be aware that DI may recur in subsequent pregnancies, particularly if there is an underlying condition affecting liver function 5, 2

Special Considerations and Pitfalls

• Distinguishing AFLP from other high-risk liver diseases of pregnancy (HELLP syndrome, preeclampsia) can be challenging due to overlapping features 7
• Delay in diagnosis and treatment of AFLP has life-threatening consequences for both mother and fetus 7
• In cases of recurrent gestational DI, consider underlying liver disorders that may exacerbate vasopressinase activity 5
• Early referral to a transplant center should be considered for women with severe hepatic impairment 1