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Acute fatty liver of pregnancy: clinical outcomes and expected duration of recovery
David B. Nelson, MD; Nicole P. Yost, MD; F. Gary Cunningham, MD
OBJECTIVE: Our aim was to provide a description of clinical and laboratory nding: pregnancy outcomes in women with acute fatty liver of pregnancy (AFLP). We also characterize the duration of recovery of multiorgan system dysfunction that begins after delivery. STUDY DESIGN: All women who were admitted to Parkland Hospital with AFLP were identied; their clinical and laboratory ndings, pregnancy outcomes, and postpartum resolution of AFLP were reviewed. RESULTS: Between 1975 and 2012, there were 51 women who were

synthesis was impaired in more than three-fourths of the women, which served to intensify obstetric hemorrhage for which 50% of the 51 women received blood and component transfusions. The stillbirth rate was 120 of 1000 pregnancies, and there were 2 maternal deaths. Composite recovery times of various markers of hepatic and renal function indicated normalization of most laboratory values within 7-10 days after delivery.
CONCLUSION: The clinical features and laboratory ndings of women with AFLP derive from the central pathologic process: liver failure. After delivery, clinical recovery typically is seen within 3-4 days; however, laboratory abnormalities can persist for much longer.

identied to have AFLP. The most common complaints were persistent nausea and vomiting (57%), hypertension (57%), and abdominal pain (53%). More than 90% of these women had at least 1 of these ndings or combinations thereof. A combination of hepatic and renal dysfunction was nearly universal, but with variable severity. Procoagulant

Key words: acute fatty liver of pregnancy, obstetric hemorrhage, renal dysfunction

Cite this article as: Nelson DB, Yost NP, Cunningham FG. Acute fatty liver of pregnancy: clinical outcomes and expected duration of recovery. Am J Obstet Gynecol 2013;209:456.e1-7.

aternal deaths from acute liver failure caused by microvesicular fatty inltration were rst described >150 years ago.1,2 In 1903, Williams3 briey cited this rare occurrence, and only sporadic cases were reported during the ensuing 4 decades.4 In 1940, Sheehan5 published detailed histopathologic ndings from autopsies of pregnant

From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX. Received April 24, 2013; revised May 29, 2013; accepted July 1, 2013. The authors report no conict of interest. Presented in part as posters at the 32nd annual meeting of the Society for Maternal-Fetal Medicine, Dallas, TX, Feb. 6-11, 2012. Reprints: David B. Nelson, MD, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390-9032. DavidB.Nelson@UTSouthwestern.edu.
0002-9378/$36.00 2013 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2013.07.006

women with acute fatty liver failure; most of these deaths were from hepatotoxicity (related to chloroform), which was a commonly used anesthetic. He termed the idiopathic cases as obstetric acute yellow atrophy. Thereafter, removal of chloroform and tetracycline antibiotic use in obstetrics obviated most cases.6,7 Burroughs et al8 later provided a meticulous pathologic description of these women as having widespread microvesicular fatty inltration of swollen hepatocytes with minimal necrosis and cholestasis. These women had moderateto-severe renal insufciency, and many of them also had profound coagulopathic changes. Over the past 20 years, maternal deaths from acute fatty liver of pregnancy (AFLP) has declined to approximately 10% along with a concomitant decrease in perinatal deaths.9-15 This is despite major morbidity that is consequential to liver failure that includes kidney injury and coagulopathy-intensifying obstetric hemorrhage. Because most investigators assume that earlier recognition of AFLP has the best maternal and fetal outcomes, recent criteria were developed that might

facilitate an earlier diagnosis or that could be used to conrm it retrospectively. One such set was the Swansea Criteria proposed by Chng et al16 and subsequently veried by the United Kingdom Obstetrical Surveillance System.11 Although it is generally agreed that recovery begins at or around the time of delivery, these reports provide only scant details concerning recovery of hepatic and renal function.9-16 The purpose of our study was to provide the clinician with a reasonable expectation of the duration of recovery of multiorgan system abnormalities that are associated with AFLP.

M ATERIALS

AND

From 1975-2012, 1 of the investigators were involved in the care of women who were admitted to Parkland Hospital with a diagnosis of AFLP. These names were entered into a registry, and with approval from the Institutional Review Boards at the University of Texas Southwestern Medical Center and Parkland Hospital, data were extracted from these medical records. For the entire study period, the criteria for diagnosis included evidence of acute liver failure with characteristic

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clinical ndings accompanied by laboratory evidence that conrmed hepatic dysfunction along with collateral multiorgan system aberrations. We also applied both the Swansea criteria proposed by Chng et al16 and the AFLP-triad of Vigil-de Gracia and Montufar-Rueda13 to conrm the diagnoses. Women were excluded if they were found to have viral hepatitis or hepatotoxicity that was caused by chemical agents and drugs. Patients with hemolysis, elevated liver enzymes, and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count syndrome) without evidence of hepatic insufciency were not considered to have AFLP. Parkland Hospital is a tax-supported institution that serves the medically indigent women of Dallas County, Texas. In conjunction with the University of Texas Southwestern Medical Center at Dallas, obstetric care is coordinated and provided throughout pregnancy, delivery, and the puerperium period by members of the divisions of obstetrics and maternal-fetal medicine. Throughout the years of this report, women who were diagnosed with AFLP were treated in relatively uniform fashion by residents who were supervised by obstetrics faculty and fellows. In brief, for evaluation of maternal and fetal status, women were admitted to the labor and delivery suite, obstetric intermediate care unit, or the medical or surgical intensive care unit. The obstetric intermediate care unit is a high-dependency unit as dened by the Society of Critical Care Medicine and previously described by Zeeman et al.17 Anesthesia residents and faculty are available on-site, and 24/7 consultation is available from medical and surgical specialty services. After evaluation and stabilization, obstetrics management, especially expediting delivery, are the mainstays of care. For this study, patient information was de-identied and stored in a computerized database. Maternal demographics, clinical ndings and laboratory results, management, delivery and pregnancy outcomes, and postpartum recovery were reviewed. Laboratory ndings were those that were determined by methods contemporaneously in use for various biochemical, hematologic, and coagulation tests. The severity and duration of hepatic necrosis were assessed by serial measurements of serum aspartate aminotransferase (AST) concentrations. The extent of liver dysfunction and recovery were assessed with serial measurements of serum cholesterol and albumin, bilirubin conjugation and clearance, and procoagulant proteins and anticoagulant activity. Acute kidney injury was determined by serial measurement of serum creatinine concentration. Additional hematologic and coagulation studies were performed as available by medical technologists in the Obstetrical Hematology Research Laboratory.18 Imaging studies were performed dependent on contemporaneous availability to include ultrasonography, computed tomography, and magneticresonance imaging. Hepatic tissue to conrm microvesicular fatty inltration was obtained by liver biopsy in 9 women and at autopsy in another 2 women.

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TABLE 1

Clinical and laboratory ndings for 51 women with acute fatty liver of pregnancy
Factor Symptoms Nausea and vomiting Hypertension Abdominal pain Jaundice Encephalopathy Laboratory Hepatic transaminase elevation (mean: 453 334 U/La) Creatinine levelb >1.0 mg/dL 1.5 mg/dL Thrombocytopenia level <150,000/mL <100,000/mL <50,000/mL Leukocytosis level: >13,000/mL Hyperbilirubinemia: >1.1 mg/dL (mean: 3.7 2.0 mg/dLa) Cholesterol levelc: <220 mg/dL (mean: 129 47 mg/dL) International normalized ratio: >1.5 Prothrombin time: >15 sec Hypobrinogenemiad <150 mg/dL <100 mg/dL Hypoglycemia
f e

Percentage 57 57 53 33 16

100

96 76 69 20 10 98 100

R ESULTS
From 1975-2012, there were 51 women with AFLP. Of these, 48 women were from the Parkland Hospital obstetrics population, and the 3 women were transferred from area hospitals. During this 38-year period, approximately 492,000 women were delivered at our hospital; thus, the frequency of AFLP was 1 per 10,000 births. With the exception of a propensity for twin gestations of 14%, their demographic characteristics were similar to women from our general obstetrics population. Their mean maternal age was 27.4 7.3 years (range, 15e42 years), and 41% of them were nulliparous. The clinical presentation of these women was variable and largely dependent on the severity of liver dysfunction. The 5 most common symptoms and their frequency are shown in Table 1. Persistent nausea and vomiting, hypertension, or abdominal pain was seen in >50% of these women, and >90% of the women had at least 1 of these symptoms or a combination thereof. As shown in Table 1, all 51 women had laboratory evidence for varying degrees of hepatocellular necrosis that was indicated by

100

60 48

49 29 18 24 27

Lipase (mean: 293 681 U/La) Ultrasonography: bright liver

a

Data presented as mean SD; b Normal serum creatinine values during pregnancy 0.4-0.9 mg/dL29; c Normal serum cholesterol values during pregnancy 220-350 mg/dL29; d Normal plasma brinogen levels during pregnancy 300-700 mg/dL29; e Hypoglycemia dened as <60 mg/dL; f Normal serum lipase values during pregnancy 41-112 U/L.29

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elevated serum transaminase levels. Hepatic dysfunction was also universal. Specically, in the 28 women in whom cholesterol levels were determined, all of the levels were abnormally decreased when compared with reference ranges for normal pregnancy; all of the women had hyperbilirubinemia, and 16% of the women had encephalopathy. Of special clinical concern, seriously diminished procoagulant factor levels were common, and one-half of all women had a plasma brinogen level of <150 mg/dL. Leukocytosis was nearly universal (98%); however, hypoglycemia (<60 mg/dL) was documented in only 18% of the women. Acute kidney injury was nearly universal, and 76% of these women had a serum creatinine level of 1.5 mg/dL. Selected demographics and pregnancy outcomes are shown in Table 2. Gestational age at delivery ranged from 31.7e40.9 weeks, and 20% of the women were delivered <34 weeks gestation. Hemorrhage from coagulopathy that was associated with liver failure was the most common complication. This was particularly problematic because of the cesarean delivery rate of nearly 50%. More than 50% of these 51 women required transfusions; of these, one-third of the women received >10 units of blood and components, and one-fourth of the women required platelet transfusions for persistent surgical oozing. Pancreatitis developed after delivery in 8 of the 51 women from 2-10 days after delivery. In none of the women was this severe, and the condition of each affected woman responded to conservative measures within 3-5 days. Peak amylase values with pancreatitis ranged from 55e1538 U/L, and peak lipase values ranged from 50e3330 U/L. There were 8 women with hepatic encephalopathy; 3 of these women underwent tracheal intubation for ventilator support or airway protection. Related to this, 1 maternal death was in a transferred woman with encephalopathy who vomited and aspirated before intubation could be performed; she died of acute respiratory distress syndrome. Shown in Figure 1 is a cross section of her liver at the time of autopsy. A second maternal death was due to fulminant liver failure with unsustainable

TABLE 2

Selected pregnancy outcomes for 51 women with acute fatty liver of pregnancy
Variable Pregnancy outcomes Gestational age, wka Twin gestation, n (%) Vaginal delivery, n (%) Cesarean delivery-overall, n (%) Live fetus, n (%) Fetal compromise, n (%) Preterm delivery, n (%) <34 wk 34-37 wk Maternal complications, n (%) Blood and components transfusion Pulmonary edema Platelet-transfusions Encephalopathy Pancreatitis Tracheal intubation Dialysis Death Perinatal outcomes Birthweight, ga Birthweight <2000 g , n (%) Stillborn, n (%) Live born, n (%) Umbilical artery pH <7.0 Neonatal intensive care unit Neonatal death
a

Measure 37.0 2.6 (31.7e40.9) 7 (14) 26 (51) 25 (49) 25 (57) 10 (40) 20 (40) 10 (20) 10 (20)

28 (55) 7 (14) 7 (14) 8 (16) 8 (16)

3 (6) 7 (14) 1 (2) 2 (4) 2545 710 (1255e4090) 10 (20) 7 (12) 4 (8) 17 (33) 0
b

Medical/surgical intensive care unit

Data are given as mean SD (range); Excludes intubations for general anesthesia.

Nelson. Acute fatty liver of pregnancy. Am J Obstet Gynecol 2013.

hypotension. In both, microvesicular steatosis was conrmed histologically. Selected perinatal outcomes are also shown in Table 2. There were 7 twin pregnancies (14%). For all infants, the birthweight range of 1255e4090 g reected gestational ages. From the total of 58 fetuses, 12% were dead at the time of admission; however, there were no further perinatal deaths. Two-thirds of these infants were male. The

overall cesarean delivery rate for these 51 women was 49%. In 10 of these 25 women, cesarean delivery was done for evidence of fetal compromise on biophysical testing. One-third of all infants were admitted to the neonatal intensive care unit for acidosis or preterm birth. Long chain L-3-hydroxyacylCoA dehydrogenase (LCHAD) mutation testing was performed in some women through analysis of fragmented DNA

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FIGURE 1

Autopsy specimen from a woman with AFLP

The liver has a greasy yellow appearance that was present throughout the entire specimen.
AFLP, acute fatty liver of pregnancy. Nelson. Acute fatty liver of pregnancy. Am J Obstet Gynecol 2013.

FIGURE 2

Serum aspartate aminotransferase, serum cholesterol, and total serum bilirubin beginning at and after delivery

Nelson. Acute fatty liver of pregnancy. Am J Obstet Gynecol 2013.

that was obtained from microdissected formalin-xed material. As previously reported, the common LCHAD mutation (G1528C [E474Q]) was not identied in 10 of these women.19 LCHAD testing had also been completed in some, but not all, of the neonates with limited value. To depict recovery of the multiple organ system dysfunctions that was caused by liver failure with AFLP, we plotted selected analytes for epochs of time after delivery. As shown in Figure 2, in general, arrest of hepatocellular necrosis was apparent within 1-2 days after delivery, as evidenced by decreasing AST levels. These levels usually peaked at or around the time of delivery, after which they dissipated rapidly to <100 U/L by the second or third postpartum day. After this, most of the levels were slightly elevated at the time of discharge; in a few women, they remained slightly elevated for up to several weeks. Recovery of hepatic function lagged behind the recovery of necrosis, as evidenced by serial serum cholesterol levels that continued to decline after delivery to reach a nadir at 3-4 days after which they began to increase (Figure 2). In like manner, serum bilirubin levels either remained static or increased. In addition to diminished bilirubin conjugation and clearance, these levels were also inuenced by ongoing brisk hemolysis as seen on peripheral blood smear analysis and scanning electron microscopy. Resolution of renal dysfunction is shown in Figure 3. Importantly, note that, in all but a few of these women, a baseline serum creatinine value was veried at the time of routine prenatal laboratory testing (0.54 0.16 mg/dL) to be within the normal reference range.20 There were 2 types of renal dysfunction. The prerenal component was manifest by the rapid decline in serum creatinine values after delivery, which had decreased to <1 mg/dL by 7-10 days. There was also evidence for an acute kidney injury component, because at least 15% of these women had abnormally elevated creatinine values compared with those values that were reported by this time after a normal pregnancy.21,22 456.e4

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nearly universal mild-to-moderate thrombocytopenia. Platelet concentrations are grouped according to values greater than or <150,000/mL at the time of delivery. Both groups reached a nadir at 1-2 days after delivery; the values then plateaued and began to recover on days 4-6 after delivery. The international normalized ratio (INR) was abnormally prolonged (>1.1) in >90% of these women at presentation, and it was >1.5 in nearly 60% of the women (Table 1). As shown in Figure 4, the INR began to normalize over the next week. Finally, nearly 50% of these women at the time of presentation had a plasma brinogen level of <150 mg/dL, and in nearly onethird of the women the values were <100 mg/dL (Table 1). Fibrinogen levels began to recover at 2-3 days after delivery. Those women who were most severely affected demonstrated recovery in a linear fashion; however, this recovery period is obfuscated by aggressive blood component replacement. To correct for

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transfused brinogen, the plasma levels are shown (Figure 4, insert) to depict the computed lower levels had replacement not been given. We identied 51 women with acute fatty liver disease of pregnancy during this 38-year period for a frequency at Parkland Hospital of 1 per 10,000 births. This frequency compares with reported estimates of 1:7000 for Los Angeles County Hospital and 1:20,000 for the United Kingdom.9,11 The complications and pregnancy outcomes shown in Table 2 for these women are similar to those from 6 recent reports and conrm that most morbidity that is associated with AFLP is collateral to liver failure.9-14 In addition to reporting pregnancy outcomes of women with AFLP, our aim was to provide an estimation of the duration necessary after delivery for recovery of hepatic, renal, and hemostatic dysfunction. Previous investigators have stressed that, because of their similarity in clinical presentation, AFLP frequently is diagnosed incorrectly as HELLP syndrome.13,15,23 Although both disorders have varying incidences and degrees of associated hypertension, thrombocytopenia, and elements of hepatocellular necrosis that are characterized by elevated serum transaminase levels, the seminal difference is the sine qua non of AFLP: hepatic dysfunction. Because liver failure and the derivative complications are rarely found with HELLP syndrome, we suggest that several features will differentiate these 2 disorders. First, persistent nausea and vomiting are the most common symptoms with AFLP; however, this is reported in <15% of women with either preeclampsia or HELLP syndrome.23-26 Second, serum creatinine values are elevated more frequently and more profoundly with AFLP compared with HELLP syndrome. Specically, three-fourths of women with AFLP had a serum creatinine level of >1.5 mg/dL, whereas most women with severe preeclampsia (with or without HELLP syndrome) have creatinine levels <1.1 mg/dL.23,24 Third, hepatic steatosis with AFLP impairs cellular dysfunction sufciently to curtail hepatic production

Serum creatinine values (mean SEM) beginning at and after delivery

C OMMENT

The dashed line represents mean creatinine value at the initiation of prenatal care.
Nelson. Acute fatty liver of pregnancy. Am J Obstet Gynecol 2013.

Recovery of hematologic function is shown in Figure 4 where platelet levels and tests for procoagulant activity are plotted. Serial platelet counts reect
FIGURE 4

Platelet count, INR, PTT, and brinogen levels after delivery

The insert of brinogen gure reveals predicted brinogen levels of those women most severely affected (n 7) if component therapy was not provided (green curve) compared with actual values (red curve).
INR, international normalized ratio; PTT, partial thromboplastin time. Nelson. Acute fatty liver of pregnancy. Am J Obstet Gynecol 2013.

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FIGURE 5

Testing algorithm of basic and targeted studies for evaluation of women suspected to have AFLP

AST, aspartate aminotransferase; INR, international normalized ratio; LDH, lactate dehydrogenase; MR, magnetic resonance imaging; RBC, red blood cell. Nelson. Acute fatty liver of pregnancy. Am J Obstet Gynecol 2013.

of cholesterol and brinogen and other procoagulant proteins and to impede bilirubin conjugation and clearance with resultant jaundice. In an effort to further differentiate AFLP and HELLP syndrome, we offer a testing algorithm of basic and targeted studies to summarize the diagnostic testing performed in women with some of these common nonspecic complaints (Figure 5). Clinically, the 3 most prominent organ system derangements in women with AFLP include hepatic dysfunction, renal insufciency, and impaired procoagulant synthesis. We found that the duration of recovery after delivery for the return of normal liver function is dependent on overall disease severity. As expected, this was quite variable among these 51 women, and it was not always concordant with the severity of accompanying renal and hemostatic dysfunction. Importantly, clinical recovery was observed in most women within 3-4 days after delivery; however, return towards normal of laboratory studies lagged. That said, ongoing hepatocellular damage began to decrease soon after delivery, which was reected by rapidly declining serum AST levels during the rst 2-3 days (Figure 2). This analyte reached a plateau at 5-7 days after delivery, and although long-term follow-up was limited, 15% of women still had AST

values of >70 U/L 5 days after delivery. We found that, if these values markedly worsened after delivery, they usually were indicative of bacterial sepsis or severe hypoxic-ischemic liver damage. In contrast to hepatocellular necrosis, recovery of hepatic dysfunction took place less quickly, as indicated by more prolonged impaired cholesterol production and bilirubin conjugation and clearance (Figure 2). Although jaundice usually worsened after delivery, this was at least partially due to brisk ongoing hemolysis. Recovery of renal function was relatively prompt after delivery (Figure 3). An element of acute kidney injury is commonly reported with AFLP,9-13 and it was almost universal in women in our study. Although continued injury can lead to acute tubular necrosis,10 dialysis is required only occasionally. In the present series, it was necessary for only 1 woman who had ongoing liver failure that was subsequently fatal. Clinically, recognition of acute kidney injury is important so that drugs with renal clearance are either avoided or given in attenuated doses, such as the magnesium sulfate that we administered to 50% of our patients. From our observations, there is a major prerenal component to acute kidney injury that progressed in some women to an intrinsic insult.

Importantly, the prerenal component was rapidly reversible; most women had a linear decrease in serum creatinine levels, with a nadir to approximately 1 mg/dL, within the rst week (Figure 3). In women with intrinsic injury, the serum creatinine level at this time remained elevated when compared with levels that are expected for normal women after delivery (0.65 vs 0.53 mg/dL).21,22 Hemostatic dysfunction that had been treated vigorously up through the time of delivery remained clinically controlled after delivery. Even women with the most profound coagulopathy who were treated adequately had sufcient procoagulant synthesis for continuing clinical hemostasis after delivery (Figure 4). As a result, there was limited need for further transfusions of platelets and clotting factors after delivery. Nonetheless, normalization of these procoagulants was not complete for up to 1 week after delivery. This is illustrated by the delayed return towards normal of platelet and brinogen levels, the INR, and the partial thromboplastin time (Figure 4). Postpartum complications included recurrent bleeding from uterine atony, uterine or abdominal incisions, perineal lacerations, or intraabdominal sites. Even without postpartum hemorrhage, ongoing transfusions frequently were required because of continuing hemolysis. In addition to blood and component therapy, aggressive uid management is paramount with close observation for pulmonary edema, which is seen in 14% of women. Sepsis was masked by hypothermia, which we found to be common in these women. Pancreatitis, which developed in the puerperium in 15% of the women, has been reported to be fatal in some cases.9-15,26 Although a similar proportion of the women had pancreatitis, it was not severe in any of the women. Transient diabetes insipidus developed in 10-15% of the women with AFLP, and it may worsen oliguria. Finally, although there has been recent enthusiasm for plasma exchange for women with AFLP,27,28 our ndings do not support its use. Specically because all but 2 of the 51 women in our study recovered with supportive care alone. We also agree 456.e6

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brinogen and other procoagulants to clinically functional levels with freshfrozen plasma, cryoprecipitate, or whole blood if operative delivery is necessitated. Another aspect of resuscitation is that hemorrhage intensies severe hemoconcentration from capillary endothelial leakage; therefore, aggressive blood and uid replacement is requisite to avoid hypotension that would worsen hepatic and renal ischemia.

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14. Mellouli MM, Amara FB, Maghrebi H, et al. Acute fatty liver of pregnancy over a 10-year period at a Tunisian tertiary care center. Int J Gynaecol Obstet 2012;117:88-9. 15. Sibai BM. Imitators of severe preeclampsia. Obstet Gynecol 2007;109:956-66. 16. Chng CL, Morgan M, Hainsworth I, Kingham JGC. Prospective study of liver dysfunction in pregnancy in Southwest Wales. Gut 2002;51:876-80. 17. Zeeman GG, Wendel GD Jr, Cunningham FG. A blueprint for obstetric critical care. Am J Obstet Gynecol 2003;188:532-6. 18. Pritchard JA, Cunningham FG, Mason RA. Coagulation changes in eclampsia: their frequency and pathogenesis. Am J Obstet Gynecol 1976;124:855-64. 19. Maitra A, Domiati-Saad R, Yost NP, et al. Absence of the G1528C (E474Q) mutation in the alpha-subunit of the mitochondrial trifunctional protein in women with acute fatty liver of pregnancy. Pediatr Res 2002;51:658-61. 20. Lindheimer MD, Conrad KP, Karumanchi SA. Renal physiology and diseases in pregnancy. In: Alpern R, Hebert S, eds. Seldin and Giebischs the kidney. San Diego: Elsevier; 2007:2339. 21. Hladunewich MA, Myers BD, Derby GC, et al. Course of preeclamptic glomerular injury after delivery. Am J Physiol Renal Physiol 2008;294:F614-20. 22. Cornelis T, Odutayo A, Keunen J, Hladunewich M. The kidney in normal pregnancy and preeclampsia. Semin Nephrol 2011;31: 4-14. 23. Vigil-De Gracia P. Acute fatty liver and HELLP syndrome: two distinct pregnancy disorders. Int J Gynaecol Obstet 2001;73:215-20. 24. Martin JN, May WL, Magann EF, Terrone DA, Rinehart BK, Blake PG. Early risk assessment of severe preeclampsia: admission battery of symptoms and laboratory tests to predict likelihood of subsequent signicant maternal morbidity. Am J Obstet Gynecol 1999;180:1407-14. 25. Cooray SD, Edmonds SM, Tong S, Samarasekera SP, Whitehead CL. Characterization of symptoms immediately preceding eclampsia. Obstet Gynecol 2011;118:995-9. 26. Moldenhauer JS, OBrien JM, Barton JR, Sibai B. Acute fatty liver of pregnancy associated with pancreatitis: a life-threatening complication. Am J Obstet Gynecol 2004;190: 502-5. 27. Martin JN Jr, Briery CM, Rose CH, Owens MT, Boll JA, Files JC. Postpartum plasma exchange as adjunctive therapy for severe acute fatty liver of pregnancy. J Clin Apheresis 2008;23:138-43. 28. Jin F, Cao M, Bai Y, Zhang Y, Yang Y, Zhang B. Therapeutic effects of plasma exchange for the treatment of 39 patients with acute fatty liver of pregnancy. Discov Med 2012;13:369-73. 29. Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol 2009;114:1326-31.

with Castro et al9 that aggressive attempts for transplantation are unnecessary in all but the direst of circumstances. Our study has 2 major limitations. First, because of the observational design, we could have missed some women with AFLP. Second, histologic conrmation could not be justied in most women; thus, some of the women may not have had hepatocellular steatosis. These limitations are counterbalanced by the relatively large number of women with AFLP who were cared for in a single center over 4 decades. A strength of our study is that the maternal and fetal outcomes during this 38-year span are similar to those reported from more recent studies. An exception is our nding of hypoglycemia in only 18% of women. Although this seems relatively low when compared with other reports, we found that the comparison of hypoglycemia among reported studies was difcult because of both the variation in denition and the timing of evaluation (ie, at admission, at diagnosis, at delivery, or at the nadir).9-14 This may explain the reason that our rate of hypoglycemia at diagnosis (18%) was relatively low in consideration to other studies. As an example, Fesenmeier et al10 found a range of 11e159 mg/dL with an average at diagnosis of 81 mg/dL in 16 patients, whereas the peak nadir average was 56 mg/dL. Castro et al9 identied 28 patients of whom none were diagnosed with AFLP on admission with a glucose nadir of approximately 70 mg/dL at delivery with a range of 25e150 mg/dL. They cite an incidence of hypoglycemia of 100% but did not dene it numerically.9 The other studies are equally unrevealing.11-14 In addition, our ndings represent glucose values from the time of admission before the liver failure was maximal, which also may explain this discrepancy. In summary, our experiences with 51 women with AFLP reafrm the seriousness of the disorder in which morbidity is centered on hepatic failure that is associated with multiorgan involvement that resulted in varying degrees of clinical and laboratory derangements. It is imperative before delivery to assess the severity of coagulopathy to allow planning to restore

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