Rare, potentially fatal complication of pregnancy that occurs in the 3rd trimester or early postpartum period, characterized by a microvesicular fatty infiltration or steatosis of hepatocytes, which can precipitate coagulopathy, electrolyte imbalance, and multi-organ failure.
Pregnancy-associated liver diseases:
- Preeclampsia with hepatic impairment
- Haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome
- Hyperemesis gravidarum
- Intrahepatic cholestasis of pregnancy
- Acute fatty liver of pregnancy (AFLP)
History:
“Acute yellow atrophy of the liver,” a rare and fatal complication of pregnancy, was first described by Stander and Cadden in 1934.
The first documented inherited disorder of fatty acid oxidation was described in 1973 of a muscle carnitine palmitoyl transferase (CPT) deficiency. Since then, more than 20 different disorders that affect β-oxidation have been identified. LCHAD deficiency was first described in 1989. MTP deficiency was first reported in 1992, which cleared the confusion of interpreting the combined defects of LCEH, LCHAD, and LKAT.
Pathophysiology
Mitochondrial β-oxidation of fatty acids:
Complex process that consists of multiple transport steps and 4 enzymatic reactions resulting in the sequential removal of 2-carbon, acetyl-coenzyme A units.
Fatty acid oxiadtion (FAO) disorders:
Category of inborn errors of metabolism that are inherited in an autosomal recessive pattern which cause defects in mitochondrial β-oxidation
- Long chain hydroxyacyl CoA dehydrogenase (LCHAD) deficient fetus (M/C, 20% cases)
- Mitochondrial trifunctional protein (MTP) deficient fetuses
In the latter stages of pregnancy, the primary source of energy for the mother shifts to fats, while glucose is the primary energy substrate for the fetus. In an inherited defect in fat metabolism, this defect would be expected to become clinically manifest in late pregnancy, when the maternal dependence on fats as the primary source of energy is at its peak.
Other risk factors:
- First pregnancy
- Male foetus
- Materal obesity
Presentation
Severe coagulopathy, jaundice, hepatic encephalopathy, ascitis, hypoglycemia, and a mild to moderate elevation of transaminase levels are the key features of AFLP.
Initial manifestations: Nonspecific
- Headache, fatigue
- Nausea and vomiting (70%)
- Right upper quadrant (RUQ) or epigastric pain (50%-80%)
- Hypertension, proteinuria, oedema (ovelapping HELLP/preeclampsia)
Complications
AFLP can be complicated at an early stage due to the decreased liver production of coagulation factors and/or DIC
- Disseminated intravascular coagulopathy (DIC)
- Upper gastrointestinal hemorrhage (due to coagulation abnormalities)
- Acute renal failure
- Infection
- Pancreatitis
- Hypoglycemia
- Hepatic encephalopathy (late complication)
- Hepatorenal syndrome (late complication)
- Postpartum hemorrhage (PPH) (high postpartum risk)
- Complications during recovery phase:
- Diabetes insipidus
- Pancreatitis
Diagnosis
Swansea criteria:
predictor of hepatic microvesicular steatosis
Lab investigations:
- ↑AST & ALT
- ↑ S. bilirubin
- Hypoglycemia
- Hypoalbuminemia
- Thrombocytopenia
- ↑ S. urea, uric acid, creatinine
- Elevated ammonia and white blood cell count may be present.
- Coagulopathy: ↑ PT, ↑ INR, ↓ fibrinogen.
Differential diagnosis:
- HELLP syndrome
- Preeclampsia
Management
Treatment of AFLP entails a combination of maternal stabilization and prompt delivery of the fetus regardless of gestational age.
Immediate termination of pregnancy
Irrespective of gestational age