Pregnant Woman, 39, With Hypertension and New-Onset Proteinuria

Disturbances in the hepatocytes due to excess fatty acids impair the liver’s ability to convert unconjugated bilirubin into conjugated bilirubin, causing plasma levels of unconjugated bilirubin to rise. This increase in bilirubin explains the jaundiced appearance of women with AFLP. AFLP is often thought to occur in conjunction with preeclampsia in many, but not all, patients. Thrombocytopenia in these patients is felt to be secondary to peripheral vascular consumption. Conjugated bilirubin levels may also be increased due to decreased flow of conjugated bilirubin into the common bile duct.²¹

Another liver function that is disrupted is that of glycogen storage and conversion to glucose, and the liver’s ability to convert nutrients into glycogen is also impaired. Decreased storage of glycogen, along with the liver’s inability to break down previously stored glycogen, causes a decrease in serum glucose levels. Women with AFLP often require treatment with IV dextrose in response to marked hypoglycemia.^16,21,23

The liver dysfunction associated with AFLP reduces adequate production of clotting factors and coagulation proteins. Thrombocytopenia, elevated clotting times, and bleeding are all problems seen in AFLP. Mild to moderate elevations in serum aminotransferases and elevated LDH also occur in patients with AFLP.^23,24

Genetic Factor
There is little known about the etiology of AFLP, although recent data point to a genetic component that was found in as many as 62% of mothers in one study and in 25% of infants in another study.^20-22 Fatty acid oxidation (FAO) is one of the processes of hepatic mitochondria, a process that relies on several enzymes. When FAO is interrupted, fatty acids are deposited in the liver cells, as seen in histologic studies of AFLP.^25,26 The common thread in women with this disease is a mutation in one of the enzymes needed for FAO. This enzyme is the long-chain 3-hydroxyacyl-CoA dehydrogenase. Deficiencies in this enzyme are common in mothers with AFLP and their infants.^{3,16,20,23,27}

Differential Diagnosis
Several complications of pregnancy that involve the liver may, on presentation, mimic AFLP.^{16,20,23,24,28} The most common are hyperemesis gravidarum and intrahepatic cholestasis of pregnancy²³ (see Table 2^{16,20,23,24,28}); others are preeclampsia/eclampsia and HELLP syndrome. It is important to distinguish between the signs and symptoms associated with each of these disorders in order to provide the most effective treatment. Hepatitis serologies are important in the differential diagnosis when liver enzyme levels are exceptionally high.^4,16,22,28

Treatment
The most effective treatment for AFLP is delivery of the infant; often, this alone causes the signs and symptoms of AFLP to resolve.^8,21,27,29 In two of three cases in a small study by Aso et al,⁸ early delivery of the fetus led to complete resolution of symptoms and return to normal liver function. One of these patients was sent home four days after delivery; the other, 14 days later. Other patients may require more invasive treatment and support.⁸

Management in the ICU is often required to provide appropriate supportive care to the mother after delivery. Acute respiratory distress syndrome, pancreatitis, hemorrhage, encephalopathy, renal failure, and continual liver failure are among the severe complications associated with AFLP.^4,8,10 Many women require intubation, dialysis, fluid resuscitation, blood product transfusion, and vasopressor therapy.^3,8,11 Prophylactic antibiotics, IV steroids, and glucose may all be required in the supportive care and recovery of a mother with AFLP.^3,8,11

TPE has also been useful in instances of severe complications.1,3,6 In one retrospective study, Martin et al¹ recommended administration of TPE in patients with AFLP under the following circumstances:

(1) Deteriorating central nervous system abnormalities, such as sensorium changes or coma;

(2) Persistent coagulopathy requiring continued and aggressive blood product support with plasma, red cells, and/or cryoprecipitate;

(3) Advanced renal dysfunction that compromised fluid management;

(4) Progressive cardiopulmonary compromise; and/or

(5) Ongoing fluid management concerns, including significant ascites, edema, anuria/oliguria, and/or fluid overload.¹

In rare cases, liver transplantation is needed in patients with AFLP. Westbrook et al¹⁸ reviewed 54 cases of liver disease in pregnancy in one UK hospital between 1997 and 2008. Of these, six patients with encephalopathy or elevated lactate were listed for liver transplant, including just one with a diagnosis of AFLP. This woman never actually underwent transplant but recovered in response to medical management alone.¹⁸ According to data reported in June 2011 by the Organ Procurement and Transplantation Network,³⁰ liver transplantation was needed in only three US patients with AFLP between 2000 and 2011. Further retrospective studies on outcomes from transplant versus medical management should be considered to guide future decision making involving this invasive therapy.

The Case Patient
This 39-year-old patient presented during a routine prenatal visit with proteinuria and hypertension, possibly indicative of preeclampsia. Because of the serious nature of this potential diagnosis in pregnancy, she was admitted for monitoring and further testing. Although the diagnosis of AFLP was not confirmed until later, the patient’s preliminary lab studies showed elevated liver enzymes and low platelet counts, signifying the need for prompt intervention and delivery of the infant. At this point, the patient met criteria for HELLP syndrome, but AFLP was suspected after the initial finding of profound hypoglycemia led to further testing.