Acute fatty liver of pregnancy

Signs and symptoms

Acute fatty liver of pregnancy (or hepatic lipidosis of pregnancy) usually manifests in the third trimester of pregnancy, but may occur any time in the second half of pregnancy, or the puerperium, the period immediately after delivery. The usual symptoms in the mother are non-specific including nausea, vomiting, anorexia (or lack of desire to eat) and abdominal pain; excessive thirst may be the earliest symptom without overlap with otherwise considered normal pregnancy symptoms;

In patients with more severe disease, pre-eclampsia may occur, which involves elevation of blood pressure and accumulation of fluid (termed oedema). hepatic encephalopathy, and pancreatitis. There have also been reports of diabetes insipidus complicating this condition.

Many laboratory abnormalities are seen in acute fatty liver of pregnancy. Liver enzymes are elevated, with the AST and ALT enzymes ranging from minimal elevation to 1000 IU/L, but usually staying in the 300-500 range. Bilirubin is almost universally elevated. Alkaline phosphatase is often elevated in pregnancy due to production from the placenta, but may be additionally elevated. Other abnormalities may include an elevated white blood cell count, hypoglycemia, elevated coagulation parameters, including the international normalized ratio, and decreased fibrinogen. Frank disseminated intravascular coagulation, or DIC, may occur in as many as 70% of people.

Abdominal ultrasound may show fat deposition in the liver, but, as the hallmark of this condition is microvesicular steatosis (see pathology below), this is not seen on ultrasound. Rarely, the condition can be complicated by rupture or necrosis of the liver, which may be identified by ultrasound.

Pathophysiology

The understanding of the causes of acute fatty liver of pregnancy has been improved by advances in mitochondrial biochemistry. Deficiency of LCHAD (3-hydroxyacyl-CoA dehydrogenase) leads to an accumulation of medium and long chain fatty acids. When this occurs in the foetus, the unmetabolized fatty acids will re-enter the maternal circulation through the placenta, and overwhelm the beta-oxidation enzymes of the mother. LCHAD deficiency is autosomal recessive in inheritance and mothers are often found to be heterozygous for the affected mutation.

Diagnosis

The diagnosis of acute fatty liver of pregnancy is usually made on clinical grounds by the treating physician, but differentiation from other conditions affecting the liver may be difficult. The diagnosis of acute fatty liver of pregnancy is suggested by jaundice with a lesser elevation of liver enzymes, elevated white blood cell count, disseminated intravascular coagulation, and a clinically unwell patient.

A liver biopsy can provide a definitive diagnosis, but is not always done, due to the increased chance of bleeding in acute fatty liver of pregnancy. Often testing will be done to exclude more common conditions that present similarly, including viral hepatitis, pre-eclampsia, HELLP syndrome, intrahepatic cholestasis of pregnancy, and autoimmune hepatitis.

Pathology

If a liver biopsy is needed for diagnosis of the condition, the mother should be appropriately stabilized and treated to reduce bleeding-related complications. The diagnosis can be made by a frozen section (as opposed to a specimen in formalin) that is stained with the Oil red O stain, which shows microvesicular steatosis (or small collections of fat within the liver cells). The microvesicular steatosis usually spares zone one of the liver, which is the area closest to the hepatic artery. On the regular trichrome stain, the liver cell cytoplasm shows a foamy appearance due to the prominence of fat. Necrosis is rarely seen. The diagnosis can be enhanced by electron microscopy, which can be used to confirm the presence of microvesicular steatosis, and specifically the presence of megamitochondria and paracrystalline inclusions. Liver diseases with similar appearances include Reye's syndrome, drug-induced hepatitis from agents with mitochondrial toxicity, including nucleoside reverse transcriptase inhibitors used to treat HIV, and a rare condition known as Jamaican vomiting sickness which is caused by the eating of the unripened Ackee fruit.

Treatment

Acute fatty liver of pregnancy is best treated in a centre with expertise in hepatology, high-risk obstetrics, maternal-fetal medicine, and neonatology. Physicians who treat this condition will often consult with experts in liver transplantation in severe cases. Admission to the intensive care unit is recommended.

Initial treatment involves supportive management with intravenous fluids, intravenous glucose, and blood products, including fresh frozen plasma and cryoprecipitate to correct DIC. The foetus should be monitored with cardiotocography. After the mother is stabilized, arrangements are usually made for delivery. This may occur vaginally, but, in cases of severe bleeding or compromise of the mother's status, a caesarian section may be needed. Often, AFLP is not diagnosed until the mother and baby are in trouble, so it is most likely that an emergency C-section is needed.

The complications of acute fatty liver of pregnancy may require treatment after delivery, especially if pancreatitis occurs.

Epidemiology

Acute fatty liver of pregnancy is a rare condition and occurs in approximately one in 7,000 to one in 15,000 pregnancies. Mortality of the foetus has also diminished significantly, but remains 23%, and may be related to the need for premature delivery.

History

The disease was first described in 1940 by H. L. Sheehan as an "acute yellow atrophy" of the liver, then thought to be related to delayed chloroform poisoning.

References

References

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