CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2013;11:1392–1398

Interpretation and Management of Hepatic Abnormalities in Pregnancy

LEILA KIA and MARY E. RINELLA

Department of Medicine, Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois

related changes in sex hormones have direct effects on biliary

Podcast interview: www.gastro.org/cghpodcast. smooth muscle contractility and modulate biliary transporters,
Also available on iTunes. these changes do not produce symptoms in normal pregnancy.4
In some cases, hormone-induced changes in biliary transport
and metabolism can lead to symptomatic cholestasis. For the
The spectrum of liver disease in pregnancy includes liver most part, abnormalities in liver chemistries in the context of
disease unrelated to pregnancy, liver diseases that occur with normal pregnancy are limited to an increase of alkaline phos-
increased frequency or severity in pregnancy, and liver disease phatase level (placental origin) and a decrease in albumin level
specific to pregnancy. Diseases of the liver unique to pregnancy (as a result of hemodilution) and are not indicative of pathology
reliably occur at specific points in the gestational spectrum. unless markedly abnormal or accompanied by other hepatic
Thus, gestational age, a comprehensive history, and a clinically abnormalities.
driven diagnostic evaluation is critical in approaching a
pregnant patient with abnormal liver chemistries or function.
Newly Acquired Liver Disease, Not
Early recognition of these conditions is important and
Specific to Pregnancy
although management may be expectant, some patients
require targeted therapy or necessitate prompt delivery, which Abnormal liver chemistries during pregnancy should
can be life-saving to both mother and child. prompt an evaluation for pregnancy-specific diseases (guided by
gestational period) and also should involve the exclusion of liver
Keywords: Acute Fatty Liver of Pregnancy; HELLP Syndrome; disorders not specific to pregnancy, as well as those that might
Intrahepatic Cholestasis of Pregnancy. be more prevalent in pregnancy or associated with worse out-
comes. A complete history and physical, and serologic evalua-
tion guided by the nature of abnormalities (as in a nonpregnant

L iver disease in pregnancy encompasses a wide range of

disorders, ranging from abnormalities in liver chemistries
to life-threatening problems that warrant urgent intervention.
patient) should be performed. Hepatic ultrasound with Doppler
flow should be part of the initial evaluation to exclude a biliary
process or a vascular obstruction. Although not common, the
Hepatic laboratory abnormalities are seen in approximately 3% development of acute hepatic or portal vein thrombosis should
to 5% of pregnancies. The ability to discern benign etiologies be considered. Management of newly diagnosed/acquired liver
from potentially life-threatening conditions is critical when disease requires special considerations in pregnant women,
determining appropriate evaluation and management. This is particularly in those with viral hepatitis and gallstone disease.
especially true in the management of incidental abnormalities
found on routine screening of asymptomatic patients. Liver Viral Hepatitis
abnormalities in a pregnant patient can be divided into 4 cate-
gories: (1) physiologic changes in the liver during normal Viral hepatitis acquired during pregnancy can increase
pregnancy; (2) newly acquired liver disease not specific to, but both maternal and fetal morbidity and mortality in the acute
more prevalent in, pregnancy; (3) liver disease that is unique to phase.
pregnancy; and (4) pregnancy occurring in a patient with pre- Hepatitis A infection typically is acute and self-limited, and
existing liver disease (which is not covered by this review). The its management is supportive. Infection acquired in the second
management of cirrhosis, portal hypertension, and liver trans- and third trimesters can be associated with premature contrac-
plantation during pregnancy recently was reviewed elsewhere.1 tions, placental separation, premature rupture of membranes,
The goal of this review is to provide a practical guide to fetal distress, and preterm labor.5 In rare cases, fulminant hep-
evaluation and management of the pregnant patient with atitis may develop, and has been linked to poor nutritional state,
abnormal liver chemistries or function. advanced maternal age, or co-existent hepatitis B infection.
Vaccination is recommended for all women traveling to endemic
areas, and appears to be safe in pregnancy. Vertical transmission
Physiologic Changes in Pregnancy
In pregnancy, the liver is affected primarily by circula-
tory and hormonal changes. Pregnancy is associated with a Abbreviations used in this paper: AFLOP, acute fatty liver of preg-
nancy; HCV, hepatitis C virus; HELLP, syndrome of hemolysis, increased
hyperdynamic circulation in which cardiac output increases in
liver enzymes, and low platelets; HG, hyperemesis gravidarum; ICP,
the second trimester and plateaus in the third trimester, with a intrahepatic cholestasis of pregnancy; SBA, serum bile acid; UDCA,
40% increase in circulating blood volume. Blood flow to the liver ursodeoxycholic acid.
remains unchanged, but the percentage of cardiac output to the © 2013 by the AGA Institute
liver is reduced, which may impair clearance of substances 1542-3565/$36.00
requiring extensive hepatic metabolism.2,3 Although pregnancy- http://dx.doi.org/10.1016/j.cgh.2013.05.016
November 2013 HEPATIC ABNORMALITIES IN PREGNANCY 1393

to the fetus is rare, but horizontal transmission in a woman related biliary obstruction. The simplest initial test should be
caring for her newborn is possible. a transabdominal ultrasound to evaluate for the presence of
Hepatitis B infection acquired during pregnancy does not cholelithiasis and biliary ductal dilatation, although the sensi-
differ significantly from the nonpregnant patient, and treatment tivity for choledocholithiasis is only 50%.15 Abdominal imaging
mainly is supportive, except in the rare case of fulminant hep- with magnetic resonance cholangiopancreatography can be
atitis, in which lamivudine and tenofovir may be used to helpful in the evaluation of the biliary tree in this setting. It is
decrease viral load before liver transplantation or decrease the performed without gadolinium and is considered safe after
risk of fetal infection. Vertical transmission of hepatitis B is a the first trimester. In equivocal cases, endoscopic ultrasound
matter of significant concern because most affected infants can be considered, but requires sedation. Management of
become chronic carriers. Ninety-five percent of transmission choledocholithiasis and its complications may require endo-
occurs in the third trimester near the time of birth, or in the scopic retrograde cholangiopancreatography, which will expose
immediate postpartum period. The risk of transmission is the fetus to radiation, but may lead to increased morbidity
increased if the patient develops acute hepatitis B virus in the if untreated.
third trimester. Mothers who have hepatitis B e antigen posi-
tivity and high viral load (>106 copies/mL) are also at increased
risk of vertical transmission.6,7 Details relating to prophylaxis, Pregnancy-Related Liver Disease
prevention, and management of vertical transmission are Liver diseases unique to pregnancy have some overlap but
outside the scope of this review, but were outlined nicely in a generally have distinguishing features. One such feature is the time
recent review by Pan et al.8 in which they occur along the gestational spectrum (Figure 1).
Hepatitis C virus (HCV) infection typically is diagnosed in a
chronic state; however, cases of acute hepatitis C increasingly Early Pregnancy
are reported. A few case reports have described successful
Hyperemesis gravidarum. Although nausea and
management of acute hepatitis C in pregnancy, with early de-
vomiting are common in pregnancy, hyperemesis gravidarum
livery or incomplete interferon therapy, with favorable out-
(HG) is characterized by intractable nausea and vomiting,
comes for the mother and fetus.9,10 Viral replication appears to
frequently requiring hospitalization. It occurs, by definition, in
increase despite lower serum aminotransferase levels seen in
the first trimester, in 0.3% to 2.0% of pregnancies. Symptoms are
pregnancy, but they return to pre-pregnancy levels post-
typically severe enough to result in weight loss, dehydration,
partum.11 Treatment is contraindicated during pregnancy given
ketonuria, and electrolyte imbalances.16 In 10% of women,
the teratogenicity of current treatments, which include riba-
symptoms persist throughout pregnancy and resolve only with
virin. New HCV treatments with boceprevir and telaprevir have
delivery of the fetus.17,18 HG is more common in the setting of
not been studied in pregnancy, but they are both Food and
molar pregnancy, twin pregnancies, pre-existing diabetes or
Drug Administration category B and warrant further study.
hypothyroidism, and psychiatric disorders.19 The diagnosis of
Vertical transmission plays a small role in the transmission of
HG is clinical and is accompanied by abnormalities in liver
HCV. Data from a large study showed a 5.1% rate of HCV RNA
chemistries in up to 50% of cases. A hepatocellular injury
viremia at 1 year in newborns of HCV-positive mothers.12 Fac-
pattern is typical, with increases in alanine aminotransferase
tors associated with an increased risk of transmission include
and aspartate aminotransferase levels ranging from mild to as
high maternal viremia, maternal peripheral blood mononuclear
high as 10 times the upper limit of normal.20 Jaundice is rare
infection by HCV, premature rupture of membranes (>6 h), and
and when present may suggest underlying liver or biliary tract
procedures associated with exposure of the infant to maternal
disease.21 HG is a diagnosis of exclusion; thus, a careful evalu-
blood.
ation for pre-existing liver disease or other gastrointestinal
Hepatitis E infection conveys an acute risk to both the
illness is essential.
mother and fetus, with a 20% mortality rate if acquired in the
Management. Treatment is supportive, and includes
third trimester in the setting of acute hepatitis. For the fetus,
correction of dehydration and electrolyte abnormalities. Thia-
there is a higher rate of spontaneous abortion and intrauterine
mine supplementation is recommended to prevent Wernicke
death.13 In contrast to hepatitis A, vertical transmission has
encephalopathy. Although the role of corticosteroids is not well
been documented in women with acute hepatitis E, with poor
established, it may be useful in refractory cases.22 Successful
fetal outcomes. It is endemic in underdeveloped areas with poor
treatment of HG leads to correction of abnormal liver chemis-
sanitation, with the highest prevalence rates in the Indian sub-
tries without lasting liver complications (Table 1).
continent, China, Asia, Africa, and the Middle East.14 However,
prevalence in the United States has been increasing, particularly
in southern states. Management is supportive.

Biliary Disease
The onset of biliary disease during pregnancy is com-
mon, given hormonal changes and their effect on biliary smooth
muscle and bile transporters. Higher estrogen levels also pro-
mote gallstone formation through cholesterol supersaturation
of bile. In the presence of acute abdominal pain, a cholestatic
liver chemistry profile (alkaline phosphatase, g-glutamyl- Figure 1. The presentation and duration of pregnancy-related liver
transferase, and bilirubin) should raise suspicion for gallstone- disease according to gestational period.
1394 KIA AND RINELLA CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 11, No. 11

Table 1. Basic Management of Pregnancy-Related Liver Disease

Predominant
injury pattern Considerations Pregnancy-related liver disease
Hepatocellular Exclude viral, NAFLD, HG AFLOP Preeclampsia/eclampsia
AIH, Wilsons, drugs, Hydration Urgent delivery IV magnesium
and so forth Thiamine Screen newborn Control blood pressure
Mixed Correct coagulopathy, if present
Cholestatic Liver ultrasound ICP Urgent delivery
Exclude PBC, PSC if SBA>40 mm
compatible, drugs UDCA
Delivery at 38 wk
AIH, autoimmune hepatitis; IV, intravenous; NAFLD, nonalcoholic fatty liver disease; PBC, primary biliary cirrhosis; PSC, primary sclerosing
cholangitis.

Mid- to Late Pregnancy The development of ICP has little lasting consequence for the
Intrahepatic cholestasis of pregnancy. Intrahepatic mother. Morbidity typically is limited to pruritus, which often
cholestasis of pregnancy (ICP) is characterized by generalized begins in the palms and soles of the feet and resolves after de-
pruritus and biochemical evidence of cholestasis that typically livery, with normalization of serum bile acid (SBA) levels. Some
affects women during the last trimester of pregnancy, although women may present with jaundice, malabsorption, and clinically
it also can present in the late second trimester. Although rare, it significant gallstone disease.34,39 In contrast, morbidity and
is the most common pregnancy-related liver disorder, with a mortality for the fetus is increased, particularly in women with
prevalence of 1 in 1000 to 1 in 10,000.23 Geographically, it ap- SBA levels of 40 mm or greater.28,40 Specifically, ICP increases the
pears to be more common in South America, particularly in risk of preterm delivery (19%–60%), fetal distress (22%–41%), and
Chile (14%), with the native Araucanian population (24%) over- fetal loss (0.4%–1.6%).41–45 The incidence of fetal hypoxia,
represented. Some of these cases have been associated with meconium-stained amniotic fluid, and intrauterine death also
deficient dietary selenium.24,25 A higher incidence also has been appears to be higher, and recent studies have shown that de-
reported in Scandinavia (1%–2%), particularly in the winter livery at 38 weeks may improve perinatal outcomes.40,43,46
months.26–28 In North America, the incidence is less than 1%. Perinatal outcomes in patients with SBA levels less than 40
Risk factors for developing ICP include multiparity, advancing mm do not appear to be significantly worse; thus, these patients
maternal age, twin pregnancies, and a history of cholestasis should be managed symptomatically, without induction of
secondary to oral contraceptive use. The condition recurs in 60% preterm labor.28
to 70% of subsequent pregnancies, suggesting a genetic predis- Management. The treatment of ICP has evolved over
position with incomplete penetrance. the years. Studies have examined the role of antihistamines,
The etiology of ICP is not well described, but likely includes phenobarbital, benzodiazepines, cholestyramine, dexametha-
genetic, hormonal, and exogenous factors. Evidence for a strong sone, S-adenosyl-L-methionine, and ursodeoxycholic acid
genetic component is supported by familial clustering, increased (UDCA), with the latter showing the most robust data for
prevalence in specific ethnic groups, a higher incidence level in symptom amelioration and prevention of adverse fetal out-
twin pregnancies, and an increased risk in siblings of women comes.17,47–51 In patients with SBA levels of 40 mm or greater,
affected with ICP.29 The majority of genetic variation in ICP has UDCA decreases the severity of pruritus, SBA levels, alanine
been identified in the biliary transporters ATP-Binding Cassette aminotransferase, and bilirubin. Data on the impact on fetal
B (ABCB) 4 and ABCB11, with various mutations conferring complications are mixed. However, a more recent meta-analysis
increased susceptibility to ICP.30–32 Recent studies also have confirmed the safety and efficacy of UDCA in improving pru-
shown decreased expression of bile acid transporters in the ritus, liver chemistries, and fetal outcomes.52 This improvement
placenta, mainly Organic Anion-transporting Polypeptide in pruritus may be related to a direct effect of UDCA on hor-
(OATP) 1A2 and OATP1B3, in women with ICP.33 Along with monal mechanisms impairing biliary transporter function.53
genetic factors, ICP appears to have a strong hormonal associ- Interestingly, treatment with UDCA also can improve
ation. Symptom severity is highest during the third trimester, morphologic placental abnormalities present in ICP.54 Based on
when reproductive hormone concentrations are the highest.29 the current data, UDCA (10–15 mg/kg) is the preferred treat-
Pruritus also has been described in women taking exogenous ment for ICP, coupled with consideration of early delivery,
hormones and at particular points in the menstrual cycle, particularly in patients with SBAs of 40 mm or greater (Table 1).
implying a further correlation between hormonal changes and Toxemia of pregnancy. Toxemia of pregnancy en-
pruritus.34 Both estrogens (mainly estradiol-17b-D-glucuronide) compasses preeclampsia, eclampsia, and the syndrome of hemo-
and progesterone metabolites can promote cholestasis.26,35 The lysis, increased liver enzymes, and low platelets (HELLP)
latter seem to play a more important role, and studies have (Figure 2). It represents a spectrum of hepatic abnormalities that
shown an increase in 3a, 5a isomers of these metabolites in can lead to fatal complications both for the mother and the fetus.
patients with ICP, with a concurrent decrease in their biliary and Preeclampsia is present in 0.6% to 1.2% of pregnancies, of which
fecal excretion.23,36 Relationships between these metabolites and 20% of severe cases go on to develop HELLP syndrome. Risk
the farnesoid X receptor appear to mediate bile acid homeostasis factors for the development of severe preeclampsia and HELLP
pathways, as ongoing studies have shown.29,37,38 include a history of diabetes, chronic hypertension, multiparity,
November 2013 HEPATIC ABNORMALITIES IN PREGNANCY 1395

important because management and prognostic implications

differ.
The diagnosis of HELLP syndrome requires a high index of
suspicion. The majority of patients endorse nonspecific fatigue
and malaise before presentation, and 50% report epigastric or
right upper-quadrant pain. The degree of jaundice usually is
mild, and other clinical signs and symptoms may be absent. The
main abnormalities noted on biochemical examination include
varying degrees of thrombocytopenia and increased liver enzyme
levels, increased lactate dehydrogenase as a result of hemolysis,
and microangiopathic hemolytic anemia noted on peripheral
smear examination. The damage caused by microangiopathic
hemolytic anemia is thought to be caused by vascular endo-
thelial injury, fibrin deposition in blood vessels, platelet activa-
tion, and consumption.17 On histology, HELLP is characterized
by periportal or focal parenchyma necrosis with hyaline depo-
sition of fibrin material in the sinusoids; however, biopsies rarely
are performed in this setting.58 Sinusoidal obstruction likely
explains the right upper-quadrant pain experienced by most
patients. Of the several classification systems proposed for
HELLP, the most widely used is the Mississippi classification,
which stratifies severity based on platelet count and amino-
transferase level increase. Generally, thrombocytopenia less than
100,000/mm3, lactate dehydrogenase level greater than 600 U/L,
and aminotransferase levels greater than 70 U/L are consistent
with a diagnosis of HELLP.59,60 Worsening thrombocytopenia is
Figure 2. Toxemia of pregnancy and associated disease. associated with poor outcomes.
Compared with severe preeclampsia or partial HELLP,
and older age.55–57 There is a significant overlap between these women with HELLP require more blood transfusions, have a
disorders and hemolytic uremic syndrome, thrombotic throm- higher incidence of disseminated intravascular coagulation,
bocytic purpura, and acute fatty liver of pregnancy (AFLOP), acute renal failure, pulmonary edema, wound hematomas,
making them difficult to differentiate (Table 2). intracerebral hemorrhage, subcapsular liver hematomas
Preeclampsia is defined by the development of hypertension (including rupture), and death.58 Complications decrease
(140/90 mm Hg) occurring at 20 weeks gestation or later, plus significantly with advanced gestational age as fetal risk di-
proteinuria (0.3 g/24 h). Severe preeclampsia is characterized minishes, and some studies have shown this is irrespective of the
by blood pressure of 160/90 mm Hg or greater and 5 g protein/ diagnosis of HELLP versus severe preeclampsia.61
24 h or greater, or by the presence of end-organ damage (oli- Management. Management of HELLP requires im-
guria, cerebral or visual problems, pulmonary edema, impaired mediate hospitalization, often in an intensive care unit. Man-
liver function, thrombocytopenia, or fetal growth restriction).57 agement of patients with preeclampsia includes institution of
In women with pre-existing hypertension, superimposed pre- intravenous magnesium sulfate as prophylaxis against seizures,
eclampsia can be diagnosed when there are sudden changes in and antihypertensives to lower blood pressure to less than
blood pressure and proteinuria, or new thrombocytopenia and 160 mm Hg systolic. Fetal well-being should be assessed using
increased aminotransferase levels develop. Seizures in the setting standard methods and, finally, the timing of delivery should
of any of the earlier-described findings defines eclampsia. be established. Definitive management for HELLP is delivery
Finally, the finding of hemolysis, along with thrombocytopenia of the fetus, which typically results in resolution of symptoms
and increased liver enzyme levels, suggests the development of within 5 days, although complications still can present post-
HELLP syndrome, which carries the highest risk both for the partum. The general approach is to deliver the fetus if the
mother and the fetus. Distinguishing between these 3 entities is gestational age is older than 34 weeks. If younger than 34 weeks,

Table 2. Similarities and Differences Between Diseases Associated With Toxemia of Pregnancy and Other Syndromes
HUS TTP Preeclampsia Eclampsia HELLP AFLOP
Headache U U U
Acute kidney injury U U U
Low platelets U U U U U U
Altered mental status U U U
Fever U
Hypertension U U
Seizure U
Increased liver chemistries U U U U U U
Disseminated intravascular coagulopathy U U
HUS, hemolytic uremic syndrome; TTP, thrombotic thrombocytic purpura.
1396 KIA AND RINELLA CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 11, No. 11

the administration of glucocorticoids followed by delivery in aminotransferase levels. Jaundice is not common, and signs of
48 hours is preferred. However, there is considerable debate preeclampsia may be present. In cases of acute liver failure, en-
regarding the timing of delivery and the utility of administering cephalopathy and coagulopathy may be part of the initial clin-
corticosteroids in cases of HELLP. Randomized controlled trials ical presentation. Although the mechanism is not clear, polyuria
are needed to validate current practice.62 Conservative therapy is and polydipsia are noted in about 5% of cases and are almost
not effective, although a recent case report using eculizumab, a pathognomonic for AFLOP once diabetes has been ruled out.72
targeted inhibitor of complement C5, prolonged pregnancy by Although serum aminotransferase levels are increased, they are
17 days without adverse events.63 In most cases, both maternal lower than what one sees in the setting of acute viral hepatitis.
and fetal complications are common without prompt delivery. Hypoglycemia also may be noted, which is uncommon in other
In the setting of hemodynamic instability from the development pregnancy-related liver diseases. Thrombocytopenia also is
of hepatic subcapsular hematoma and hemorrhagic shock, common, but this also can be seen in HELLP and preeclampsia,
surgical exploration, percutaneous embolization of the hepatic as noted previously. The diagnosis of AFLOP is based on clinical
artery, and liver transplantation all have been pursued with criteria, imaging suggestive of steatosis (although because it is
some success64–66 (Table 1). microvesicular fat, it is not seen reliably on imaging), and liver
Acute fatty liver of pregnancy. AFLOP is a rare biopsy showing microvesicular fatty change (Figure 3). The
condition that affects 1 in 7000 to 20,000 pregnancies, almost Swansea criteria have been proposed to screen for AFLOP
exclusively in the third trimester.67–69 It is more common in without the need for liver biopsy. This algorithm has a high
nulliparous women and in twin pregnancies. It is characterized negative predictive value, but does not help to distinguish from
by microvesicular fatty infiltration of the liver, and is associated other causes of liver disease in pregnancy, which somewhat
with varying degrees of hepatic failure. It can be complicated by limits its usefulness.68,73,74 More recently, Vigil-de Gracia and
encephalopathy, thrombocytopenia, disseminated intravascular Montufar-Rueda75 proposed an “AFLOP-triad” including
coagulopathy, and renal failure, potentially resulting in symptoms, laboratory findings, and complications suggestive of
maternal and fetal death.16 It never develops after delivery, AFLOP that should trigger an evaluation to rule out AFLOP.
although the clinical course can linger after delivery and can be Although liver biopsy is the gold standard, it carries risk and
difficult to distinguish from HELLP because 50% of patients should be pursued only when the diagnosis is in question and/
with AFLOP have co-existing preeclampsia. or urgent delivery is not optimal.
The pathophysiology of AFLOP is largely unknown, but Management. AFLOP is an obstetric emergency that
many cases have been linked to fetal defects in mitochondrial requires urgent delivery to prevent maternal and fetal compli-
fatty acid oxidation, specifically in defects in 2 key enzymes: the cations. Signs of acute liver failure (coagulopathy, encephalop-
mitochondrial trifunctional protein and its a subunit, long- athy) require monitoring in an intensive care unit, with
chain-3-hydroxyacyl-coenzyme A dehydrogenase.70 The corre- supportive care, which may include intracranial pressure
sponding mutation that is associated most commonly with monitoring in some centers. Delivery results in resolution of
these defects is G1528C/E474Q. The exact mechanism by symptoms and hepatic recovery for the mother, but close
which deficiencies in these enzymes lead to clinical AFLOP is monitoring is required for the child because of the risk of an
unknown. However, one hypothesis suggests that the accu- associated fatty acid oxidation defect. Some investigators
mulation of 3-hydroxyacyl metabolites produced by the fetus is advocate screening newborns of mothers with AFLOP to assist
toxic and can lead to disease in a predisposed mother.71 Despite with genetic counseling and nutritional therapy.76 Thanks to
the association between long-chain-3-hydroxyacyl-coenzyme A advances in intensive care support, early detection of AFLOP,
dehydrogenase deficiency and AFLOP, only 20% of babies born and improved principles of early delivery, maternal mortality has
to mothers with AFLOP have the mutation. decreased from 90% to less than 10% over the past 30 years.72,77
Women typically present in the third trimester with nausea, Fetal mortality previously was reported to be 50% but also has
vomiting, and abdominal pain, in the setting of increased serum decreased substantially to levels similar to current maternal

Figure 3. (A) Microvesicular hepatic steatosis as seen in AFLOP. (B) Macrovesicular hepatic steatosis with cellular ballooning, as seen in nonal-
coholic steatohepatitis. Note that there may be some small droplet fatty change in the setting of nonalcoholic steatohepatitis, macrovesicular fat as
shown in panel B should not be prominent in AFLOP. Also note that the nucleus is displaced laterally and compressed in macrovesicular steatosis, in
contrast to microvesicular steatosis where it is centrally located. H&E, 40.
November 2013 HEPATIC ABNORMALITIES IN PREGNANCY 1397

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Reprint requests
elevated liver enzymes, and low platelets syndrome. Clin Perinatol
Address requests for reprints to: Mary E. Rinella, MD, Associate
2004;31:807–833, vii.
Professor of Medicine, Division of Gastroenterology and Hepatology,
59. Joshi D, James A, Quaglia A, et al. Liver disease in pregnancy.
Arkes Family Pavilion Suite 1400, 676 North Saint Clair Street,
Lancet 2010;375:594–605.
Chicago, Illinois 60521. e-mail: m-rinella@northwestern.edu; fax: (312)
60. Magann EF, Martin JN Jr. Twelve steps to optimal management of
908-6192.
HELLP syndrome. Clin Obstet Gynecol 1999;42:532–550.
61. Abramovici D, Friedman SA, Mercer BM, et al. Neonatal outcome in Conflicts of interest
severe preeclampsia at 24 to 36 weeks’ gestation: does the HELLP The authors disclose no conflicts.