Williams Manual of Pregnancy Complications, 23 ed.

CHAPTER 62. Acute Fatty Liver of Pregnancy

Acute liver failure of pregnancy—also called acute fatty metamorphosis or acute yellow atrophy—is the most common cause of acute liver failure in pregnant women. In its most severe form, it has an estimated incidence of 1 in 10,000 pregnancies. Current evidence suggests that some, if not all, cases of acute fatty liver of pregnancy are associated with recessively inherited mitochondrial abnormalities of fatty acid oxidation, the most common of which is a deficiency of long-chain 3-hydroxyacylcoenzyme A dehydrogenase (LCHAD). Women who are heterozygous for this mutation carrying a homozygous LCHAD-deficient fetus appear to be at increased risk to develop acute fatty liver of pregnancy.

CLINICAL PRESENTATION

Acute fatty liver usually manifests late in pregnancy with a reported mean gestational age of 37.5 weeks (range, 31 to 42). The disease is more common in nulliparas with a male fetus and in multifetal gestations. Typically, there is onset over several days to weeks of malaise, anorexia, nausea and vomiting, epigastric pain, and progressive jaundice. In many women, vomiting is the major symptom. In perhaps half of these women, there is hypertension, proteinuria, and edema—signs suggestive of preeclampsia.

DIAGNOSIS

Laboratory abnormalities include hypofibrinogenemia and prolonged clotting studies, hypocholesterolemia, hyperbilirubinemia, and modest elevations in the serum transaminase levels (usually less than 1,000 U/L). The coagulopathy results primarily from impaired hepatic production of procoagulants and to a lesser degree from increased consumption. There are variable elevations of fibrin-split products or D-dimers. Profound endothelial cell activation results in hemoconcentration, hepatorenal syndrome, ascites, and sometimes permeability pulmonary edema. Blood counts often reveal maternal leukocytosis, thrombocytopenia and anemia, the latter of which is due to hemolysis. As a result, peripheral blood smears demonstrate echinocytes and nucleated red cells.

Various imaging techniques, such as sonography, computed tomographic scanning, and magnetic resonance imaging, have been found to have a poor sensitivity to confirm the clinical diagnosis of acute fatty liver of pregnancy.

In many women, the syndrome worsens after diagnosis. Marked hypoglycemia and obvious hepatic encephalopathy are common, with severe coagulopathy and evidence for renal failure seen in about half of the women with acute fatty liver. Fetal death is more common at this severe stage. Fortunately, delivery arrests rapid deterioration of liver function.

MANAGEMENT

The principle management objectives are intensive supportive care and expeditious delivery. Significant procrastination in affecting delivery may increase the maternal and fetal risks. Some fetuses are already dead when the diagnosis is made, likely secondary to maternal acidosis; and in these cases, vaginal delivery is preferred. Viable fetuses often tolerate labor poorly, which presents a management dilemma if the mother is coagulopathic. Cesarean delivery with uncorrected coagulopathy may prove life threatening for the mother. Transfusions with variable amounts of fresh-frozen plasma, cryoprecipitate, whole blood, packed red blood cells, and platelets are usually necessary if surgery is performed or if lacerations complicate vaginal delivery.

Following delivery, hepatic dysfunction begins to resolve. In the interim, intensive medical support may be required. Two associated medical conditions may develop during this time. About 25 percent of women will develop transient diabetes insipidus caused by elevated serum vasopressinase concentrations, and up to half will develop acute pancreatitis.

With supportive care, recovery is usually complete. Maternal deaths are reported to be caused by sepsis, hemorrhage, aspiration, renal failure, pancreatitis, and gastrointestinal bleeding. Therapy is directed toward these complications. In recalcitrant cases, plasma exchange and even liver transplantation have been reported.


For further reading in Williams Obstetrics, 23rd ed.,

see Chapter 50, “Hepatic, Gallbladder, and Pancreatic Disorders.”