doi:10.1111/j.1447-0756.2010.01242.

J. Obstet. Gynaecol. Res. Vol. 36, No. 4: 751756, August 2010

Clinical diagnosis and treatment of acute fatty liver of

pregnancy: A literature review and 11 new cases
jog_1242

751..756

Qiang Wei, Li Zhang and Xinghui Liu

Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China

Abstract
Aim: To determine the clinical presentation, biochemical ndings, complications, clinical diagnosis and management of patients with acute fatty liver of pregnancy (AFLP). The inuence of the mode of delivery on
maternalperinatal mortality is analyzed and two methods of diagnostic imaging are compared.
Material & Methods: Eleven cases of AFLP identied at the West China Second Hospital of Sichuan University from January 2003 to June 2008 were studied. To provide additional evidence, 342 cases of AFLP were
reviewed retrospectively from original articles researched in the China National Knowledge Infrastructure
between the same period.
Results: All cases presented with a prodrome of nausea, vomiting, malaise and jaundice. Raised transaminases
and serum bilirubin were found in all patients (100%), hypoglycemia was found in two patients (18.2%) and
hypoproteinemia was found in ve patients (45.5%). All cases were conrmed by diagnostic criteria and
clinical assessment. Diagnostic imaging helped to conrm the diagnoses. Ultrasound was used to diagnose
nine patients (81.8%), and two (18.2%) patients were diagnosed by computerized tomography. Except for one
patient whose labor was induced with oxytocin because of fetal death before admission, all other pregnancies
were terminated by cesarean section within 24 h of denitive diagnosis. All patients and neonates survived
delivery. One (9.1%) maternal death and one (7.2%) fetal death occurred.
Conclusions: Early diagnosis, termination of pregnancy by Cesarean section as soon as possible and comprehensive therapy are crucial for improving the prognoses of both mother and newborn.
Key words: acute fatty liver of pregnancy, diagnosis, treatment.

Introduction
Acute fatty liver of pregnancy (AFLP) is a rare, but
potentially fatal, complication of the third trimester of
pregnancy. Its exact pathogenesis is unknown despite
the accumulation of a signicant amount of data
about the disease. The incidence of AFLP is 1/7000 to
1/16000.1 Although mortality due to AFLP has
declined in recent years, it is important to further
lower the mortality rate by early diagnosis and
treatment of this disease. Some cases of AFLP
have been analyzed retrospectively for improvement
of comprehensive knowledge. Many studies have

evaluated clinical presentation, laboratory values,

diagnosis, and maternalperinatal outcomes in
patients with AFLP. Fewer studies have analyzed the
inuence of the mode of delivery on maternal
perinatal mortality. The aim of the present study was
not only to explore the clinical presentation, biochemical ndings, complications, clinical diagnosis,
management, and maternalperinatal outcomes in
patients with AFLP, but also to analyze the inuence
of the mode of delivery on maternalperinatal mortalities and to compare two methods of diagnostic
imaging examinationultrasound and computerized
tomography (CT).

Received: April 6 2009.

Accepted: September 29 2009.
Reprint request to: Dr Xinghui Liu, Department of Obstetrics and Gynecology, West China Second Hospital, Sichuan University,
Chengdu 610041, Sichuan, China. Email: xinghuiliu@163.com

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Q. Wei et al.

Methods
From January 2003 to June 2008, 11 cases of AFLP were
identied at the West China Second Hospital, Sichuan
University. Presenting symptoms, clinical course, laboratory values, maternal complications, clinical diagnosis, management and maternalperinatal outcomes
were studied. The mean maternal age at diagnosis
was 27 years (range 2134 years). The mean gestational
age at AFLP diagnosis was 36.4 weeks (range
2838 weeks). All patients were primigravidae. There
were nine single pregnancies and two twin pregnancies. Fetal sex included nine males and four females.
The diagnosis of AFLP was made on the basis of
clinical and laboratory criteria as follows: (i) patients
with symptoms of anorexia, fatigue, nausea, vomiting,
jaundice and abnormal liver function in the third trimester of pregnancy; (ii) characteristic laboratory
examination; (iii) ultrasound imaging showing fatty
liver; (iv) viral hepatitis, pharmaceutic hepatitis, toxic
hepatic and other hepar diseases complicating pregnancy were excluded by laboratory examination; and
(v) liver biopsy in accordance with pathologic changes.
All cases conformed to the diagnostic criteria mentioned above, except for liver biopsy. Because of their
severe conditions, prolonged prothrombin times,
reduced platelet counts, and/or the patients refusal,
two patients did not receive liver biopsy.
Furthermore, as additional research, 342 cases of
AFLP were reviewed retrospectively from original
articles searched in the China National Knowledge
Infrastructure between January 2003 and June 2008. In
our data, all patients conformed to the diagnostic criteria mentioned above. In the present study, the data was
mainly used to analyze the clinical diagnosis, the inuence of the mode of delivery on maternalperinatal
outcomes, and to compare the two methods of diagnostic imaging used in the examination of patients
diagnosed with AFLP. The contents of this research will
be embodied in the discussion.

Results
Of the 11 patients, all cases presented with anorexia,
fatigue, nausea, vomiting, jaundice and abnormal liver
function in the third trimester of pregnancy. Five cases
had disseminated intravascular coagulation (DIC), four
had renal insufciency, two had hypertensive disorder
complicating pregnancy, three had edema and ascites,
three had hepatic encephalopathy, ve had hypoproteinemia, one had upper gastrointestinal hemorrhage,

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one had postpartum hemorrhage, and two were

hypoglycemic (Table 1).
The abnormal laboratory results of the 11 cases were
as follows: elevated hepatic aminotransferase levels
(alanine aminotransferase and aspartate aminotransferase), total bilirubin, direct bilirubin, blood urea
nitrogen, creatine, and leukocytosis; decreased platelet
counts; and prolonged prothrombin time. Some
patients also had hypoproteinemia and hypoglycemia
(Table 2). Hepatitis screening was negative in all
patients.
Both ultrasound and CT are used to diagnose AFLP,
but ultrasound is used more frequently. The 11 patients
in this study underwent ultrasound examinations.
Nine images displayed a bright hepatic echo pattern,
indicating fatty liver disease. Two of the cases underwent CT, which indicated decreased liver density. Nine
patients underwent liver biopsy; histological examination of the tissue, stained with oil red O, was consistent
with AFLP. Because of their serious conditions, prolonged prothrombin times, decreased platelet counts,
and/or the patients refusal, two cases did not receive
liver biopsy (Table 1). To compare the two methods of
diagnostic imaging, 342 cases from the original articles
searched in the China National Knowledge Infrastructure between January 2003 and June 2008 and the 11
cases included in our study (353 cases in total) were
reviewed retrospectively. Ultrasound examination was
performed on 237 of the cases; 189 (79.7%) of the scans
exhibited a bright hepatic echo pattern. CT examination
was performed on 34 of the cases; 28 (85.3%) of the
images showed decreased liver density. The rate of
positive AFLP diagnosis was 79.7% by ultrasound, and
85.3% by CT. There was no signicant difference
between the two methods (c2 = 1.22, P > 0.05).
According to the clinical presentations, laboratory,
and imaging examination results, 11 cases in our hospital were diagnosed with AFLP within one day of
admission and were given active supportive therapy.
Except for one patient, whose labor was induced with
oxytocin because of fetal death before admission, the
pregnancies were terminated promptly by cesarean
section within 24 h of denitive diagnosis. All patients
and neonates survived. Four neonates, whose Apgar
scores were less than seven at one min, were discharged by their pediatricians after full recovery. Five
of the mothers improved after their pregnancies were
terminated and were discharged at an average of 7 d;
six cases worsened after cesarean section, exhibiting
darker jaundice, ascites, oliguria, hepatic encephalopathy, and bleeding tendencies, and were treated with

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Acute fatty liver of pregnancy

Table 1 The overall summary of the 11 AFLP patients

Number
of cases
Clinical complications
Disseminated intravascular coagulation
Renal insufciency
Hepatic encephalopathy
Hypoproteinemia
Hypoglycemia
Postpartum hemorrhage
Upper gastrointestinal hemorrhage
Pre-eclampsia
Multiple organ failure
Diagnosis
Ultrasound
Computerized tomography
Liver biopsy
Delivery mode
Cesarean section
Induced with oxytocin
Pregnant outcome
Maternal death (cesarean section)
Maternal death (induction)
Perinatal death (cesarean section)
Perinatal death (induction)

Percentage
(%)

5
4
3
5
2
1
1
2
1

45.5
36.4
27.3
45.5
18.2
9.1
9.1
18.2
9.1

9
2
9

81.8
100
100

10
1

90.9
9.1

1
0
0
1

9.1
0
0
7.7

Table 2 The laboratory results of the eleven AFLP patients

Contents

Range

Average

Reference
value

Alanine aminotransferase (U/l)

Aspartate aminotransferase (U/l)
Total bilirubin (umol/l)
Direct bilirubin (umol/l)
Albumen (g/l)
Blood urea nitrogen (mmol/l)
Creatine (umol/l)
Prothrombin time (sec)
Platelet (109/l)
Leukocyte (109/l)
Glucose levels(mmol/l)

67425
46578
78445
60370
1832.5
6.941.0
68659.6
17.935.6
40126
8.621.8
1.910.8

134.6
278.9
156.2
102.5
23.6
15.7
217.5
28.7
58.9
14.6
5.4

050
050
2.024.0
07.0
3650
1.787.14
30.697.3
8.514.5
100450
4.010.0
<11.1

aggressive supportive therapy, such as protection of

the liver, therapy to affect jaundice reduction, therapy
to diminish liver enzymes, correction for coagulation
dysfunction, and antibiotic therapy. Three cases
accepted articial liver plasma exchange eight times in
total. Five cases were discharged in stable condition
and one case ultimately died. The patient who died of
multiple organ failure 2 d after admission appeared
oliguric, displayed hepatic encephalopathy, and upper
gastrointestinal hemorrhage. Her condition quickly
deteriorated after cesarean section. Ultimately, one
maternal patient and one perinatal patient died. In our

data, all pregnancies were terminated by cesarean

section, and there was no vaginal delivery data available for comparison (Table 1). Therefore, to explore the
choice of delivery mode, 353 cases were analyzed retrospectively and 332 patients with denitive delivery
mode as a result. Of the 332 patients, 228 pregnancies
were terminated by cesarean section, and of those
cases, 37 (16.2%) died. Vaginal delivery was used in 104
of the cases, resulting in 50 (48.1%) deaths. The mortality rate of the mothers who underwent cesarean section
(16.2%) was lower than those who delivered vaginally
(48.1%). There was a signicant difference between the

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Q. Wei et al.

Table 3 The overall summary of the 353 AFLP patients

Number
of cases
Clinical complications
Disseminated intravascular coagulation
Renal insufciency
Hepatic encephalopathy
Hypoproteinemia
Hypoglycemia
Postpartum hemorrhage
Upper gastrointestinal hemorrhage
Pre-eclampsia
Multiple organ failure
Diagnosis
Ultrasound
Computerized tomography
Liver biopsy
Delivery mode
Cesarean section
Vaginal delivery
Pregnant outcome
Maternal death (cesarean section)
Maternal death (vaginal delivery)
Perinatal death (cesarean section)
Perinatal death (vaginal delivery)

two mortalities (c2 = 20.42, P < 0.01). Furthermore,

there were 270 perinatal survivals and 32 (10.6%)
deaths among the cesarean section group; in the
vaginal delivery group, there were 100 perinatal survivals and 36 (26.5%) deaths. The perinatal mortality rate
with cesarean section (10.6%) was lower than the mortality rate with vaginal delivery (26.5%). There was a
signicant difference between the two mortalities
(c2 = 9.85, P < 0.01).
In addition, an overall summary on the 353 patients
including the clinical complications, diagnosis, management, pregnant outcome are present in Table 3.

Discussion
AFLP is a late-gestational complication, often occurring
at 2840 weeks (mean 36 weeks). It is reported that
being primigravida, having had multiple pregnancies,
carrying a male fetus, and experiencing preeclampsia
are the high-risk factors for AFLP. Despite of extensive
investigations for the genetic origins of pre-eclampsia
and related diseases, the causes of hemolysis, elevated
liver enzymes, and low platelet count syndrome
(HELLP syndrome) and AFLP have not been claried
yet.24 Pre-eclampsia occurs in approximately 50% of
AFLP cases, and 15% of cases are associated with multiple pregnancies.5,6 The morbidity ratio for AFLP

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Percentage
(%)

145
140
112
198
232
111
86
108
82

41.1
39.7
31.7
56.1
65.7
31.4
24.4
30.6
23.2

189
28
55

79.7
85.3
100

228
104

68.7
31.3

37
50
32
36

16.2
48.1
10.6
26.5

between male and female fetuses is 3 : 1. Our data conforms to the situation mentioned above. Because the
initial symptoms of AFLP are atypical and could be
neglected, and because this disease develops rapidly
and causes multi-system dysfunction in a very short
time, it is important to be especially vigilant for its
development. Summarizing the data from 353 cases,
AFLP should be highly suspected when the following
clinical conditions occur: (i) gastrointestinal symptoms,
which include nausea, vomiting, fatigue, and vague
abdominal pain, appearing in late pregnancy without
obvious reason; (ii) jaundice occurring after gastrointestinal symptoms and promptly becoming worse; (iii)
liver dysfunction occurring in late pregnancy, when
other hepatic diseases have been excluded; (iv) laboratory examination showing obvious leukocyte elevation,
decreased red blood cells and platelets, elevated total
bilirubin, especially direct bilirubin, and an increase in
hepatic aminotransferase levels (ALT, AST) from mild
to moderate (the variable range was reported from
normal to 1000 U/L and seldom over 500 U/l. Most
research reports the mean to be approximately 200 U/
l.); (v) hypertensive disorder complicating pregnancy
associated with hypoglycemia, hypobrinogenemia,
and increased prothrombin time; (vi) maternal coagulation dysfunction complicated with fetal distress in
late pregnancy without denitive reason; and (vii)

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Acute fatty liver of pregnancy

ultrasound scan of a fatty liver showing increased

echogenicity (bright liver), and a CT indicating
decreased liver density.
In recent years, non-invasive methods have often
been used for early diagnosis of AFLP. In our study, the
rate of positive AFLP diagnosis was 79.7% by ultrasound, and 85.3% by CT. There was no signicant difference between the two methods (c2 = 1.22, P > 0.05).
In practical work, both ultrasound and CT are the most
common methods for clinical diagnosis of fatty liver.
For convenience and safety, ultrasound is seen as the
preferred method in liver screening. Liver biopsy is
the gold standard to conrm fatty liver. However, it is
the focus of debate at present, and is restricted to clinical use in patients whose conditions are complicated by
DIC. Liver biopsy needs to be performed early in the
preliminary diagnosis, before the occurrence of DIC.
Therefore, we suggest the routine use of ultrasound or
CT for early diagnosis of AFLP.
Once AFLP is diagnosed or highly suspected, pregnancy should be terminated as soon as possible,
regardless of whether the condition is mild or severe or
the course is early or late. Castro7 thinks that AFLP is an
idiopathic disease of pregnancy. It is known as reversible peripartum liver failure because the biochemical
and pathologic changes recover after termination of the
pregnancy and proper treatment. Some researchers810
reported that if the interval from occurrence of AFLP to
delivery was one week, 100% of patients survived. If
the interval from the occurrence of AFLP to delivery
was more than 2 weeks, 30% (1/3 of patients) died the
same day or the day after delivery. In our data, all
pregnancies were terminated within 24 h of highly suspected or diagnosed AFLP, and the prognosis was
good. Therefore, timely termination of pregnancy is
crucial in the treatment of AFLP. There is no unied
conclusion as to the selected mode of pregnancy termination. If vaginal delivery cannot be achieved quickly,
cesarean section is the preferred method, as it is benecial to stop the progress of the patients condition
and to shorten labor as much as possible. In our
data, the mortality rate of the mothers who underwent
cesarean section (16.2%) was lower than those who
delivered vaginally (48.1%). There was a signicant difference between the two mortalities (c2 = 20.42,
P < 0.01). Furthermore, the perinatal mortality rate
with cesarean section (10.6%) was lower than the mortality rate with vaginal delivery (26.5%). There was a
signicant difference between the two mortalities
(c2 = 9.85, P < 0.01). Therefore, we suggest that cesarean
section is the preferred method to terminate pregnancy

if vaginal delivery cannot be performed promptly. In

addition, before surgery, it is important to supplement
fresh frozen plasma, platelets, and packed red blood
cells for patients with coagulation dysfunction to
reduce blood loss. When coagulation dysfunction
exists, patients have an additional degree of risk with
cesarean section; in these cases, a longitudinal incision
is benecial to reduce bleeding. Because the probability
of postpartum hemorrhage is high, hysterectomy and
uterine artery embolization should be considered at
the time of pregnancy termination.
Most patients experienced complications, such as
severe liver and kidney failure, hepatic encephalopathy, and DIC, and when analyzing the cause of death
in the 353 cases, multiple organ failure was the most
common cause and accounted for 70.1% of the deaths.
The crucial factors for successful emergency rescue are
both timely active comprehensive treatment and
obstetric therapy. Treatment consists of the following:
(i) in the early period of the disease, supportive
therapy should be provided, such as a diet low in fat
and protein, and high in carbohydrates, ensuring sufcient energy and correcting hypoglycemia to protect
the liver. In the later stages of the disease, if the patient
is unable to eat, parenteral and enteral nutrition are
necessary; (ii) the patients condition is often complicated by DIC and postpartum hemorrhage, which
could easily result in shock therefore it is important to
recover an effective blood volume, improve microcirculation, and correct hypoproteinemia by giving
blood components, such as fresh frozen plasma, platelets, packed red blood cells, and whole fresh blood, as
soon as possible; (iii) plasma exchange and hemodialysis can help eliminate endotoxins, complement
coagulation factors, and reduce platelet aggregation.
These should be given to patients with oliguria,
anuria, azotemia, and hyperkalemia as early as possible; (iv) broad-spectrum antibiotics, which have little
impact on liver and renal function, are chosen to
prevent infection; (v) attention should be given to correcting dehydration, and electrolyte and acid-base
balance; and (vi) treatments to protect the liver,
reduce jaundice, and diminish liver enzymes should
be performed as early as possible. In addition, condition rebound caused by premature withdrawal of
treatment should be avoided.
In recent years, liver transplantation and human
fetal liver cell transplantation have been used to treat
AFLP with a great deal of success.1113 However, on the
basis of active comprehensive treatment, researchers
have applied articial liver support systems, such as

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the molecular absorbents recirculating system and

plasma exchange, to treat AFLP with good results. In
our data, 3 out of the 11 cases accepted 8 plasma
exchange treatments in total in the early period of their
disease, and their conditions obviously improved after
treatment. The articial liver support system effectively
reduced maternal mortality, and its use is warranted
more commonly in clinical work, as it is more practicable than liver transplantation. After delivery, the
clinical presentation of AFLP may disappear gradually,
and the pathologic changes in the various organs
recover within months. Furthermore, after delivery,
supportive treatment and close observation are
required. Contraceptives and other drugs that can
damage the liver should be prescribed with caution.
After active treatment, the condition of most mothers
improves, with good prognosis.

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