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Background

Acute fatty liver of pregnancy (AFLP) is a serious complication unique to pregnancy first described bySheehan in 1940.[1] It is characterized by microvesicular steatosis in the liver. The foremost cause ofAFLP is thought to be due to a mitochondrial dysfunction in the oxidation of fatty acids leading to anaccumulation in hepatocytes. The infiltration of fatty acids causes acute liver insufficiency, whichleads to most of the symptoms that present in this condition. If not diagnosed and treated promptly,AFLP can result in high maternal and neonatal morbidity and mortality.

Pathophysiology

The exact pathophysiology of AFLP is unknown. AFLP is unique to pregnancy. There does notappear to be a predilection for any geographical area or race. It appears to occur more commonly inprimiparous women than multiparous women.

Women who develop AFLP are more likely to have a heterozygous long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency. LCHAD is found on the mitochondrial membraneand is involved in the beta oxidation of long-chain fatty acids. This gene mutation is recessive;therefore, outside of pregnancy under normal physiological conditions, women have normal fatty acidoxidation. However, if the fetus is homozygous for this mutation, it will be unable to oxidize fatty acids.

These acids are passed to the mother, who, because of diminished enzyme function, cannotmetabolize the additional fatty acids. This results in hepatic strain leading to the development ofAFLP, which can be relieved by delivery of the infant.[2]

Epidemiology

Frequency

United StatesAFLP affects 1 in 7000 to 1 in 16,000 deliveries. There is a predilection for nulliparous women andwomen with multiple gestations.

Mortality/Morbidity

Due to advances in diagnostic strategies and supportive care, maternal mortality and perinatal

morbidity of AFLP has declined. In the 1980s, Kaplan reported a mortality rate for both mother andfetus of about 85%.[3] Maternal mortality is now estimated to be 12.5-18%, with a neonatal mortalityrate of 7-66%.[4, 5]

While laboratory abnormalities may persist after delivery, in rare cases patients may progress tohepatic failure with the need for liver transplantation.[6]

Morbidity of the infant includes increased risk of cardiomyopathy, neuropathy, myopathy, nonketotichypoglycemia, hepatic failure, and death associated with fatty acid oxidation defects in newborns.

Race

No ethnic or regional variability is apparent.

SexThis condition is unique to pregnancy and therefore only affects women.

Age

This condition can affect any woman of child-bearing age.

History

Clinical presentation of acute fatty liver of pregnancy (AFLP) is nonspecific, and the patient canpresent with the following complaints:

Malaise

Nausea and vomiting (70%); this may present for the first time in the third trimester

Right upper-quadrant and epigastric pain (50-80%)[7] Upper gastrointestinal hemorrhage

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Acute renal failure

Infection

Pancreatitis

Hypoglycemia

Fulminant liver failure with hepatic encephalopathy

Physical

On physical examination, the patient may present with the following:

Hypertension

Bleeding

Confusion and altered mental status

Jaundice: Hyperbilirubinemia resulting in jaundice is rarely encountered in patients with severepreeclampsia. When jaundice is present in pregnancy, AFLP should be high on the differential.

Differentials

Drug-Induced Hepatotoxicity

Eclampsia

HELLP Syndrome

Hepatitis, Viral

Preeclampsia

Toxicity, Acetaminophen

Laboratory Studies

The following laboratory studies can be evaluated to help make the diagnosis of acute fatty liver ofpregnancy (AFLP).

Aspartate transaminase (AST) and alanine transaminase (ALT) are not elevated in normalpregnancies. These can become elevated in many different conditions during pregnancy. Some areunique to pregnancy, such as preeclampsia/eclampsia, HELLP, and AFLP. High levels of ALT canbe seen in patients with viral hepatitis; however, the highest levels are seen in patients with acutetoxic liver injury, as can be seen in acetaminophen overdose.[8] Both AST and ALT can be elevateddue to the hepatic injury.

Hepatic injury results in decreased gluconeogenesis and, therefore, decreased blood glucose levels. Liver detoxification is also affected, resulting in elevated levels of blood ammonia, especially late in

the disease course.

In addition, laboratory findings may be consistent with disseminated intravascular coagulation (DIC),specifically, prolongation of prothrombin time, low fibrinogen, and low antithrombin levels. Thisresults in a clinical picture similar to DIC; however, in AFLP, the values are abnormal, not due toconsumption of the clotting factors but rather to decreased production by the damaged liver. [9]

Bilirubin levels are elevated. This elevation is primarily the conjugated form, with levels exceeding 5mg/dL. This can result in jaundice, which is rarely seen in patients with other forms of pregnancy-related hepatic injury, including preeclampsia.

Some patients may develop pancreatitis, which can result in elevated amylase, lipase, andincreased blood sugars.

As the maternal kidneys become affected, blood creatine and uric acid can become elevated,leading to metabolic acidosis.

Imaging Studies

Imaging studies have a low sensitivity for diagnosing AFLP and should not be used to exclude thediagnosis. Liver ultrasonographic examination may reveal increased echogenicity in severe cases. Acomputed tomography (CT) scan may show decreased or diffuse attenuation in the liver. [10]

Histologic Findings

Although the criterion standard for diagnosis of AFLP is liver biopsy, this is rarely performed in clinicalpractice due to the risk of hemorrhage. In addition, AFLP can easily be differentiated from viral ordrug-induced hepatitis by obtaining viral serologies and measuring acetaminophen levels in serum.

If a biopsy is performed, the histological findings demonstrate pericentral microvesicular fat infiltration

with minimal inflammation or necrosis.[8]

http://emedicine.medscape.com/article/169814-overviewhttp://emedicine.medscape.com/article/169814-overviewhttp://emedicine.medscape.com/article/253960-overviewhttp://emedicine.medscape.com/article/253960-overviewhttp://emedicine.medscape.com/article/185463-overviewhttp://emedicine.medscape.com/article/185463-overviewhttp://emedicine.medscape.com/article/820200-overviewhttp://emedicine.medscape.com/article/820200-overviewhttp://emedicine.medscape.com/article/820200-overviewhttp://emedicine.medscape.com/article/185463-overviewhttp://emedicine.medscape.com/article/253960-overviewhttp://emedicine.medscape.com/article/169814-overview

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Medical Care

Delivery of the fetus, regardless of gestational age, is the only treatment for acute fatty liver ofpregnancy (AFLP) once the diagnosis has been made.

Mode of delivery is dependent on the following several factors:

Fetal status: Many fetuses demonstrate evidence of asphyxia and hypoxia; therefore, closemonitoring of fetal status is necessary, along with the ability to expedite delivery should fetalcompromise be evident.[11]

Maternal coagulation status: Due to coagulation abnormalities that can accompany AFLP, patientsmay need to have replacement of their coagulation factors should cesarean delivery be necessary.

Likelihood of success with induction of labor: If delivery cannot be safely accomplished within 24hours from the time of diagnosis, then cesarean delivery may be optimal.

Management of the severe hypoglycemia that may occur is necessary to avoid coma and death.Patients require at least a 5% Dextrose solution to maintain blood glucose levels. Blood glucoseshould be monitored closely until hepatic function returns and the patient tolerates a regular diet.

Renal function can also be affected by several factors, including maternal hemorrhage, which canlead to acute tubular necrosis and hepatorenal syndrome. Fluid balance should be closely monitored,

as patients may develop pulmonary edema due to low plasma oncotic pressures.

Martin et al reported on using postpartum plasma exchange to treat severe cases of AFLP in thepostpartum period. Patients with severe encephalopathy, on ventilator support, or with severe liver orrenal insufficiency who failed to respond to conventional management, underwent plasma exchange.All patients showed improved signs and laboratory values.[12]

Surgical Care

No specific surgical treatment exists for AFLP. Because of coagulation problems, careful evaluation ofthe genital tract for lacerations after vaginal delivery or maintaining good hemostasis duringcesareandeliveryshould be practiced.[13]

Not all types of anesthesia can be used in patients with AFLP as some are hepatotoxic with

decreased hepatic blood flow. Regional anesthesia may be obtained if a coagulopathy is not evident.However, if a coagulopathy is present, it should be corrected prior to regional anesthesia as bleedingat the puncture site is a concern. Withgeneral anesthesia, the anesthesiologist should be careful notto use agents that have potential hepatotoxicity, such as halothane. Isoflurane has no hepatotoxicityand may improve hepatic blood flow.

urther Inpatient Care

Ending the pregnancy by delivery of the infant invariably results in resolution of the hepaticdysfunction and accompanying complications that occur in acute fatty liver in pregnancy (AFLP).

Prognosis

The prognosis for women who develop AFLP is excellent, assuming they survive the acute event.

However, a case ofchronic pancreatitishas been described, occurring about 3 months after recoveryand discharge from the hospital.[14]

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