6. Acute Fatty Liver of Pregnancy

Quick Recap

This completes the Obstetrics System - all 6 protocols now have Quick Recap sections.

Obstetrics System, Protocol 6/6 — completing the Obstetrics System.

1. Definition

Acute fatty liver of pregnancy (AFLP) = a rare but potentially FATAL complication of pregnancy, characterized by MICROVESICULAR FATTY INFILTRATION of hepatocytes, resulting in acute and often PROFOUND liver failure. Distinct from HELLP syndrome (a preeclampsia-spectrum thrombotic microangiopathy with hepatic involvement) and from viral/other causes of acute liver failure in pregnancy — AFLP has its own specific hepatocyte-level pathophysiology (fat deposition rather than microangiopathic injury), though clinical overlap with HELLP can make the two difficult to distinguish at presentation.

2. Diagnosis

Diagnosis is LARGELY CLINICAL — recognizing the syndrome in the appropriate obstetric context (typically third trimester) with a compatible laboratory pattern, rather than relying on a single definitive test.

Supportive laboratory indices:

• Hypoglycemia (often <60 mg/dL) — a distinctive, actionable finding given the fat-infiltrated liver's impaired gluconeogenesis capacity; this is a genuinely useful discriminator from HELLP, where hypoglycemia is not a typical feature, and its presence should raise AFLP specifically on the differential
• Hyperammonemia — reflecting the severity of hepatic synthetic/detoxification failure
• Elevated aminotransferases (AST/ALT)
• Thrombocytopenia
• Hypofibrinogenemia
• DIC — can develop as part of the severe hepatic failure picture, overlapping with the coagulopathy management principles in the DIC protocol (Hematology System)

Liver biopsy is the GOLD STANDARD for definitive diagnosis (showing the characteristic microvesicular steatosis), but is RARELY NEEDED clinically — the combination of clinical context + supportive labs is generally sufficient to proceed with treatment, and prompt delivery (Section 3) itself most commonly results in RAPID RETURN of liver function, making an invasive biopsy an unnecessary delay in most cases rather than a required diagnostic step before treatment.

3. Treatment — Delivery as the Definitive Intervention

Once the patient is stabilized, DELIVERY SHOULD BE PERFORMED to improve both maternal resuscitation and neonatal survival — delivery is the definitive treatment, analogous to the delivery-as-treatment principle established for preeclampsia/eclampsia and HELLP syndrome elsewhere in this system, but here specifically because removing the pregnancy-driven metabolic/hormonal stressor allows the fat-infiltrated liver to begin recovering.

Sequence: STABILIZE the mother FIRST, THEN deliver — do not rush to delivery in a hemodynamically or metabolically unstable patient without first addressing acute derangements (hypoglycemia correction, coagulopathy correction, hemodynamic stabilization) that would make delivery itself more dangerous; this mirrors the general "maternal stabilization takes priority, fetal status often improves once mother is stabilized" principle from the Eclampsia protocol.

Prompt delivery MOST COMMONLY results in RAPID RETURN of liver function — an important, genuinely reassuring prognostic point distinguishing AFLP from many other causes of acute liver failure, where recovery is far less certain or rapid; this should inform family counseling once delivery has occurred.

Rarely, patients do NOT improve after delivery, and LIVER TRANSPLANTATION is required — a recognized but uncommon outcome; maintain vigilance for lack of expected post-delivery improvement as a trigger to escalate toward transplant evaluation rather than assuming recovery is inevitable.

4. Immediate Stabilization (ABCDE)

Circulation/Metabolic — the core pre-delivery stabilization priorities:

• Aggressive correction of hypoglycemia — frequent glucose monitoring and dextrose supplementation given the liver's impaired gluconeogenic capacity; this is a distinctive, ongoing management need throughout the AFLP course, not just a one-time correction
• Coagulopathy correction per the general principles in the DIC and Coagulopathy protocols (Hematology System) — bleeding-driven blood product support (FFP, cryoprecipitate for hypofibrinogenemia, platelets), particularly important given delivery itself (especially cesarean) will create a hemostatic challenge in an already coagulopathic patient
• Hyperammonemia management: supportive, similar in principle to the general hepatic encephalopathy approach (see Hepatic Encephalopathy protocol, GI & Hepatology System) if altered mental status accompanies the ammonia elevation, though AFLP-specific evidence for lactulose/rifaximin use is not well established the way it is in cirrhotic HE — treat symptomatically and prioritize delivery as the definitive intervention rather than extrapolating the full cirrhotic-HE pharmacologic approach
• Standard obstetric critical care framework applies otherwise: anticipate difficult airway, two large-bore IVs, Foley catheter, left lateral positioning to prevent supine hypotension syndrome (same principles as the Eclampsia protocol)

Checklist:

5. Differential Diagnosis

HELLP syndrome (overlapping presentation, but AFLP's hypoglycemia/hyperammonemia pattern and more profound synthetic liver failure help distinguish it — see HELLP Syndrome protocol for that entity's distinct hemolysis/platelet/liver-enzyme pattern), viral hepatitis, other causes of acute liver failure in pregnancy, cholestasis of pregnancy (typically less severe, pruritus-predominant, without the profound synthetic dysfunction of AFLP), preeclampsia/eclampsia with hepatic involvement.

6. Investigations

Glucose (frequent monitoring given hypoglycemia risk), ammonia, AST/ALT, coagulation panel + fibrinogen, platelet count, bilirubin, renal function (concurrent AKI can occur in severe cases), CBC, liver imaging (ultrasound) to assess for other structural causes and support the clinical picture, liver biopsy only if diagnostic uncertainty persists and would change management (rarely needed given the treatment approach does not depend on histologic confirmation).

7. Organ Support

Aggressive glucose correction/monitoring; coagulopathy correction (FFP/cryoprecipitate/platelets per bleeding-driven indication); standard critical care hemodynamic support; delivery as the definitive intervention once stabilized; liver transplantation evaluation for the rare non-improving case; standard ICU supportive care throughout.

8. Consultation Matrix

9. Monitoring Framework

Frequent glucose checks (ongoing, not just at presentation), serial coagulation panel/fibrinogen, serial LFTs/ammonia trend (expect improvement post-delivery; lack of improvement is a red flag), renal function, mental status (hyperammonemia-related), fetal monitoring until delivery.

10. Complications

Severe hypoglycemia, hemorrhage from coagulopathy (compounded by delivery, especially cesarean), DIC, hepatic encephalopathy-like presentation from hyperammonemia, progression to fulminant liver failure requiring transplantation (rare but recognized), renal failure, fetal complications. Prevention: aggressive proactive glucose monitoring/correction, coagulopathy correction before delivery where feasible, prompt delivery once stabilized rather than prolonged pre-delivery observation. Rescue: standard DIC/hemorrhage management, liver transplant evaluation and listing if post-delivery recovery does not occur, standard supportive care for AKI/encephalopathy if they develop.

11. Escalation & De-escalation

Escalate: hemodynamic/metabolic instability precluding safe delivery -> intensify stabilization (glucose, coagulopathy correction) before proceeding; lack of expected post-delivery liver function recovery -> escalate to hepatology/transplant evaluation.

De-escalate: delivered, liver function trending toward normal (the expected, common trajectory) -> wean supportive measures, transition to standard postpartum monitoring with continued LFT/coagulation surveillance until normalization.

12. ICU Discharge Criteria

Delivered, liver function (LFTs, coagulation panel, ammonia) trending toward normal or normalized, glucose stable without ongoing supplementation need, no evidence of progression toward transplant-requiring liver failure, hemodynamically stable.

13. Documentation & Medicolegal Checklist

14. Key Guidelines

Care of the Pregnant Patient in the ICU chapter. Washington Manual of Critical Care, 4th ed, 2025 (Ch. 71) — primary reference for this protocol.

15. Controversies

The precise threshold for pursuing liver biopsy in AFLP when the diagnosis is uncertain (vs proceeding empirically to delivery-focused management) is not tightly standardized, and practice varies based on how confidently the clinical/laboratory picture distinguishes AFLP from HELLP or other causes. The degree to which AFLP and HELLP represent points on a shared pathophysiologic spectrum versus genuinely distinct entities remains an area of ongoing clinical and research discussion, given their substantial presentation overlap.

16. References

1. Care of the Pregnant Patient in the ICU (Acute Fatty Liver of Pregnancy section). Washington Manual of Critical Care, 4th ed, 2025 (Ch. 71).
2. Nelson DB, Byrne JJ, Cunningham FG. Acute fatty liver of pregnancy. Obstet Gynecol. 2021;137(3):535-546.

See also: HELLP Syndrome and Eclampsia (Obstetrics System) for the closely overlapping presentation and shared "delivery as definitive treatment" principle; DIC and Coagulopathy (Hematology System) for the coagulopathy management framework; Hepatic Encephalopathy and Acute Liver Failure (GI & Hepatology System) for the general hepatic failure management principles this protocol partially adapts.

This completes the Obstetrics System (6/6 protocols).