What is the difference between HELLP (Hemolysis, Elevated Liver enzymes, and Low Platelet count) syndrome and Acute Fatty Liver of Pregnancy?

From the Guidelines

HELLP syndrome and Acute Fatty Liver of Pregnancy (AFLP) are distinct pregnancy complications that require prompt recognition and management, with AFLP carrying a higher maternal mortality risk and potentially requiring more intensive liver support. Both conditions typically occur in the third trimester and share features like elevated liver enzymes and coagulopathy, but they have important differences. HELLP syndrome is characterized by Hemolysis, Elevated Liver enzymes, and Low Platelets, and is considered a severe variant of preeclampsia, often presenting with hypertension and proteinuria 1. AFLP presents with more pronounced hypoglycemia, encephalopathy, and more severe coagulopathy with markedly elevated ammonia levels. Laboratory findings can help differentiate: HELLP typically shows moderate transaminase elevations (AST/ALT 200-700 IU/L), thrombocytopenia, and evidence of hemolysis, while AFLP shows more modest transaminase elevations but severe hypoglycemia, hypofibrinogenemia, and elevated ammonia.

Key Differences and Management

• HELLP syndrome: characterized by hemolysis, elevated liver enzymes, and low platelets, with moderate transaminase elevations and thrombocytopenia 1
• Acute Fatty Liver of Pregnancy (AFLP): presents with pronounced hypoglycemia, encephalopathy, and severe coagulopathy, with modest transaminase elevations but severe hypoglycemia and hypofibrinogenemia 1
• Management for both conditions involves immediate delivery regardless of gestational age, along with supportive care including blood product transfusion, glucose management, and blood pressure control 2
• AFLP may require more intensive liver support and carries a higher maternal mortality risk (7-18% vs 1% for HELLP) 3

Recommendations

• Daily aspirin prophylaxis for patients at risk for pre-eclampsia or HELLP syndrome is advised beginning at week 12 of gestation 2
• Genetic testing for long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency should be considered after AFLP as it increases recurrence risk in future pregnancies 1
• Planning for delivery and timely evaluation for possible liver transplantation is crucial in managing liver diseases unique to pregnancy 2

From the Research

Overview of HELLP Syndrome and Acute Fatty Liver in Pregnancy

• HELLP syndrome is a serious complication in pregnancy characterized by haemolysis, elevated liver enzymes, and low platelet count, occurring in 0.5 to 0.9% of all pregnancies and in 10-20% of cases with severe preeclampsia 4.
• Acute fatty liver of pregnancy (AFL) is a less common but also life-threatening complication of pregnancy, with similarities in clinical and laboratory presentations to HELLP syndrome, making differential diagnosis challenging 5.

Differential Diagnosis

• Both HELLP syndrome and AFL are characterized by microvesicular steatosis of varying degrees of severity, but a specific risk profile does not exist for either entity 5.
• Genetic defects in mitochondrial fatty acid oxidation and multiple pregnancy are considered common predisposing factors for both conditions 5.
• The diagnosis of AFL is based on a combination of clinical symptoms and laboratory findings, using the Swansea criteria as a diagnostic tool, while HELLP syndrome is a laboratory diagnosis based on the triad of haemolysis, elevated aminotransferase levels, and a platelet count < 100 G/l 5.

Clinical Features and Laboratory Findings

• Generalized malaise, nausea, vomiting, and abdominal pain are common symptoms of both diseases, making early diagnosis difficult 5.
• Clinical differences include a lack of polydipsia/polyuria in HELLP syndrome, while jaundice is more common and more pronounced in AFL, with a lower incidence of hypertension and proteinuria, and patients with AFL may develop encephalopathy with rapid progression to acute liver failure 5.
• Laboratory findings that differentiate AFL from HELLP syndrome include leucocytosis, hypoglycaemia, more pronounced hyperbilirubinemia, an initial lack of haemolysis and thrombocytopenia < 100 G/l, as well as lower antithrombin levels < 65% and prolonged prothrombin times 5.

Treatment and Management

• The only causal treatment for both diseases is immediate delivery, with expectant management between 24 + 0 and 33 + 6 weeks of gestation recommended for HELLP syndrome, but only in cases where the mother can be stabilized and there is no evidence of fetal compromise 5.
• Corticosteroids have been shown to improve platelet count, reduce liver enzyme abnormalities, and prolong latency to delivery in a dose-dependent manner in patients with HELLP syndrome 6, 7.
• High-dose corticosteroid therapy has been found to be more effective than standard-dose therapy in improving platelet count and reducing liver enzyme abnormalities in patients with HELLP syndrome 6.