Acute fatty liver of pregnancy (AFLP) is a rare disorder that typically presents in the third trimester. We report a case of a 21-year-old woman with a history of intrauterine fetal demise at 19 weeks’ gestation who developed fulminant liver failure 1 week after the fetal demise. She was diagnosed with AFLP as per the Swansea criteria. An orthotopic liver transplant was attempted but was unsuccessful. AFLP usually presents between the 30th to 38th weeks of gestation. However, it can occur in the postpartum period after only 19 weeks of gestation as highlighted in our case.
Acute fatty liver of pregnancy (AFLP) is a rare disorder with an incidence ranging from 1 : 7000 to 1 : 15000 [
A 21-year-old woman with a history of intrauterine fetal demise at 19 weeks with resulting spontaneous delivery followed by dilatation and curettage (D&C) presented to the hospital 1 week later with a 2-day history of progressively worsening right upper quadrant abdominal pain and nonbilious, nonbloody emesis. She denied any dysuria, diarrhea, and vaginal discharge. She had no significant past medical history including hypertension during her pregnancy. Her only surgical history consisted of the recent D&C. She denied using tobacco, alcohol, and illicit drugs. She was on ursodeoxycholic acid only prior to admission.
An initial exam was significant for an ill appearing obese woman (body mass index 34 kg/m2) in moderate distress due to pain and normal vitals. Her abdominal examination was significant for the right upper quadrant and epigastric tenderness without distention and rigidity. Gynecologic examination revealed old blood clots but no purulence. The remainder of her exam was normal. Initial labs were significant for aspartate aminotransferase (AST) 49 IU/L (normal 0-37 IU/L), alanine aminotransferase (ALT) 70 IU/L (normal 0-35 IU/L), alkaline phosphatase (ALP) 80 IU/L (33-123 IU/L), total bilirubin 1.3 mg/dL (normal 0-1 mg/dL), and lipase 116 U/L (normal 0-70 u/L). Basic metabolic panel, complete blood count, coagulation parameters, ethanol level, and urine drug screen were within normal limits. Acetaminophen and ethanol levels were undetectable.
Differentials at this point included pelvic infection given the recent D&C, pancreatitis, and cholecystitis. Ultrasound of the abdomen revealed increased echogenicity of the liver consistent with steatosis, gallbladder sludge, and normal common bile duct. Computed tomography (CT) of the abdomen and pelvis was negative for any acute intra-abdominal process. Pelvic ultrasound was unremarkable as well. She was started on vancomycin 1 g q12h and piperacillin-tazobactam 3.375 g q8h. The patient quickly deteriorated on hospital day 2 requiring transfer to the medical intensive care unit for altered mental status requiring intubation. CT of the head was negative for an acute intracranial process. Repeat laboratory work-up revealed sudden rise in her liver function tests (LFTs)—AST increased to 4068 IU/L, ALT increased to 1700 IU/L, total bilirubin increased to 4.8 mg/dL, conjugated bilirubin increased to 2.8 mg/dL (normal 0-0.2 mg/dL), and ALP increased to 98 IU/L—and she developed new leukocytosis (WBC
An extensive work-up for fulminant hepatic failure was pursued—repeat acetaminophen levels, methanol, hepatitis panel, autoimmune work-up including antinuclear antibody (ab), anti-smooth muscle ab, anti-mitochondrial ab, anti-liver kidney microsome ab, anti-soluble-liver-antigen ab, anti-cardiolipin ab, anti-beta-2 glycoprotein ab, and anti-lupus anticoagulant ab, ceruloplasmin levels, viral studies for Cytomegalovirus, Herpes Simplex 1, Herpes Simplex 2, Epstein Barr, and Varicella Zoster, uric acid level, alpha-fetoprotein (AFP) level, and hemochromatosis screen.
Other differentials for the sudden rise in LFTs should also include acute portal vein thrombus and pregnancy-related etiologies such as physiologic changes in pregnancy, hyperemesis gravidarum (present in the 1st trimester), intrahepatic cholestasis of pregnancy (ICP), preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), and acute fatty liver of pregnancy (AFLP). While infections and autoimmune processes can present acutely, hemochromatosis is an indolent process and was an unlikely etiology. Tylenol levels and hepatitis panel were negative. ICP was a possible etiology, however, the patient did not report any history of pruritis prior to admission. There is some clinical overlap of HELLP syndrome, preeclampsia, and AFLP which can often make it difficult to differentiate. While all these entities can have marked elevation of LFTs, the patient had no thrombocytopenia or hemolysis thus ruling out HELLP syndrome. The patient also had no evidence of hypertension or proteinuria prior to admission ruling out preeclampsia. Taken together, the findings of fulminant liver failure despite maximum medical therapy, hypoglycemia, hyperuricemia, and coagulopathy made AFLP more likely. Furthermore, the patient’s abdominal ultrasound findings were very unique in the findings of increased echogenicity which were consistent with steatohepatitis and help support a diagnosis of AFLP. These changes are not typically seen in ICP, preeclampsia, or HELLP syndrome.
As the patient had deteriorated rapidly, we started an emergent transplant evaluation. On hospital day 3, the patient’s liver function tests continued to trend upward (peak AST 11,730 IU/L and peak ALT 4190 IU/L) and she developed new onset thrombocytopenia. She also developed mild cerebral edema due to an acute rise in ammonia levels. Her infectious work-up returned negative. As she had no absolute contraindications for transplant, she underwent an orthotopic transplant on hospital day 4.
Unfortunately, her operative course was complicated by severe bleeding during the procedure and she eventually succumbed to the complications. Gross examination of her explanted liver showed a pale-yellow discoloration indicative of steatosis (Figure
Gross examination of a portion of the explanted liver exhibiting pale-yellow discoloration indicative of steatosis.
Histologic image from the liver explant demonstrating abundant microvesicular steatosis (black arrows) as well as macrovesicular steatosis (white arrow).
AFLP is a potentially fatal obstetric complication of pregnancy which is characterized by acute hepatic failure secondary to fatty infiltration of the liver. Subsequent complications of liver failure in AFLP include encephalopathy, renal insufficiency, hypoglycemia, coagulopathy, and respiratory failure. AFLP has an incidence ranging from 1 : 7000 to 1 : 15000 with most cases occurring in the third trimester [
To understand the pathophysiology of AFLP, the importance of the normal change of metabolism of fatty acids seen in pregnancy is crucial. During a normal pregnancy, there is a physiologic decrease in the oxidation of both long and medium chain fatty acids which subsequently lead to an increased maternal level of fatty acids during the course of the pregnancy, thus predisposing patients to the hepatotoxic effects of fatty acids [
More recently, our understanding of AFLP has improved after the close relation of fetal fatty acid oxidation disorders to maternal acute fatty liver disease. More specifically, the fetal deficiency of the enzyme long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) which is a component of the mitochondrial beta-oxidation of fatty acids causes accumulation of long fatty acids [
AFLP carries an autosomal recessive inheritance. Therefore, if genetically inherited, the mother is naturally at least a carrier of the mutated gene and therefore already at risk for the hepatotoxic effects of the fatty acids. Despite this known deficiency in the pathophysiology of AFLP, not all case reports have shown a fetal deficiency of this enzyme. Therefore, further pathophysiology pathways of this disease may exist.
Currently, there are no standardized guidelines on the approach to the diagnosis of AFLP. The Swansea criteria may help in making the diagnosis of AFLP when suspicion for the diagnosis is high (Table
The Swansea criteria for the diagnosis of acute fatty liver disease of pregnancy. Six or more of the following features need to be present in the absence of another explanation to diagnose AFLP.
Symptoms | Vomiting |
Abdominal pain | |
Polydipsia/polyuria | |
Encephalopathy | |
Laboratory | Leukocytosis |
Elevated transaminases | |
Elevated ammonia | |
Elevated bilirubin | |
Elevated urate | |
Hypoglycemia | |
Coagulopathy | |
Renal impairment | |
Imaging | Ascites or bright liver on ultrasound |
Pathology | Microvesicular steatosis on liver biopsy |
The mainstay of therapy is prompt delivery of the fetus. Otherwise, treatment is largely supportive with particular emphasis on treating complications of liver failure including hepatic encephalopathy, hypoglycemia, disseminated intravascular coagulation, acute renal failure, hepatic rupture, gastrointestinal bleeding, and acute respiratory distress syndrome. Patients often require admission to the intensive care unit for the management of the above [
According to a recent 2019 retrospective review of the national Scientific Registry of Transplant Recipients, data of all females in the United States undergoing liver transplantation due for AFLP (
The overall maternal mortality rates for AFLP with or without liver transplantation have markedly decreased from approximately 85% in the 1980s to approximately 10-15% in the 2000s [
Our case highlights that AFLP can rarely occur earlier in the course of pregnancy and postpartum and should therefore remain in the differential for acute hepatic failure in a pregnant patient.
The authors declare that there is no conflict of interest regarding the publication of this article.