International Journal of Gynecology and Obstetrics 118 (2012) 186–189

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International Journal of Gynecology and Obstetrics

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REVIEW ARTICLE

Pre-eclampsia/eclampsia and hepatic rupture

Paulino Vigil-De Gracia ⁎, Luis Ortega-Paz
Critical Care Unit, Department of Obstetrics and Gynecology, Caja de Seguro Social, Panama City, Panama

a r t i c l e i n f o a b s t r a c t

Article history: Objective: To review case reports of hepatic hematoma/rupture in women with pre-eclampsia/eclampsia.
Received 12 January 2012 Methods: MEDLINE, SciELO, and LILACS databases were searched for case reports of pre-eclampsia/eclampsia
Received in revised form 26 March 2012 with hepatic hematoma/rupture. Only articles written in English, Spanish, French, or Portuguese and published
Accepted 23 May 2012 between 1990 and 2010 were reviewed. Results: In total, 180 cases of hepatic hematoma or rupture were iden-
tified: 18 (10.0%) with subcapsular hematoma without hepatic rupture; and 162 (90.0%) with capsule rupture.
Keywords:
Twelve (6.7%) cases were associated with eclampsia plus hemolysis, elevated liver enzymes, and low platelet
Eclampsia
HELLP syndrome
count (HELLP) syndrome. Average age was 30.9 ± 5.0 years, 74/129 (57.4%) women were parous, and cesarean
Hepatic rupture delivery was performed in 132/162 (81.5%) cases. The right lobule was the most frequently affected 77/100
Maternal mortality (77.0%). The total maternal mortality rate was 22.2% during the 21 years; however, it decreased to 16.4%
Pre-eclampsia in the last decade studied. The perinatal mortality rate was 30.7% and was very similar during the 2 decades.
Conclusion: HELLP syndrome is a frequent diagnosis (92.8%) in hepatic hemorrhage/rupture. The major reduc-
tion in maternal mortality rate was probably associated with advances in resuscitation, intensive-care medicine,
and surgical intervention, including liver transplantation and arterial embolization.
© 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

1. Introduction The exact pathophysiology of hepatic rupture is not completely

Pre-eclampsia occurs in 8% of all pregnancies, and 10%–15% of cases
may be complicated by hemolysis, elevated liver enzymes, and low
platelet count (HELLP) syndrome, which is a life-threatening and severe
form of pre-eclampsia/eclampsia [1]. HELLP syndrome is associated with
particularly high maternal and perinatal morbidity/mortality rates
owing to pulmonary edema, cerebral edema and hemorrhage, dissemi-
nated intravascular coagulopathy, acute renal failure, hepatorenal fail-
ure, subcapsular hematoma and hepatic rupture, placental abruption,
adult respiratory distress syndrome, sepsis, stroke, and retinal detach-
ment [1,2].
Spontaneous hepatic rupture is an infrequent and life-threatening
condition of pregnancy that is virtually exclusively associated with se-
vere pre-eclampsia or HELLP syndrome. The incidence of this condition
is approximately 1 per 67 000 births or 1 per 2000 patients with pre-
eclampsia/eclampsia/HELLP syndrome [2]. There is a wide variation in
the clinical presentation and severity of the symptoms and signs of
hepatic hemorrhage/rupture. Some patients present with very mild
symptoms prior to sudden and massive circulatory collapse. However,
the clinical manifestations of hepatic hematoma include right upper
quadrant or epigastric pain, shoulder pain, and vomiting. Interestingly,
these symptoms are often present in the absence of laboratory tests [3].
⁎ Corresponding author at: Critical Care Unit, Department of Obstetrics and Gynecology,
Caja de Seguro Social, 0823-03828 Panama City, Panama. Tel.: +507 66143240; fax: +507
3909956.
E-mail address: pvigild@hotmail.com (P. Vigil-De Gracia).
understood. Liver histology findings show periportal hemorrhage and in-
travascular fibrin deposition. This pathologic condition can lead to hepat-
ic sinusoidal obstruction, intrahepatic vascular congestion, and hepatic
ischemia/infarction. In some cases, intraparenchymal and subcapsular
hemorrhages develop, and more severe cases may result in capsular
rupture [2].
A recent literature review of hepatic rupture revealed a maternal
mortality rate of 39% [4] and a perinatal mortality rate of 42% [5].
These fatality rates are high despite successes in hepatic surgery
and critical-care unit assistance [5].
The aim of the present review was to analyze case reports of
pre-eclampsia/eclampsia-associated hepatic hemorrhage or rupture
published during the past 2 decades.
2. Material and methods
A MEDLINE, SciELO, and LILACS search was conducted to find
all English-, Spanish-, French-, and Portuguese-language reports of
cases or case series of hepatic hemorrhage/rupture associated with
pre-eclampsia/eclampsia between January 1, 1990, and December 31,
2010. The following search terms were used: “eclampsia hepatic
rupture;” “preeclampsia hepatic rupture;” “HELLP syndrome hepatic
rupture;” “liver or hepatic rupture pregnancy;” and “preeclampsia-
eclampsia liver rupture.” The reference lists of articles found via this
methodology were searched for other articles reporting hepatic hemor-
rhage or rupture with HELLP syndrome during the study period. Only
publications reporting cases of hepatic hemorrhage with or without

0020-7292/$ – see front matter © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.ijgo.2012.03.042
 P. Vigil-De Gracia, L. Ortega-Paz / International Journal of Gynecology and Obstetrics 118 (2012) 186–189 187

rupture of the capsule associated with pre-eclampsia/eclampsia were Table 1

included in the analysis. Demographic and maternal findings (n = 180).

Reports of cases of hepatic hematoma/rupture were analyzed for Cases Mean ± SD Range
data variables such as demographic data, hepatic rupture, hepatic hem-
Maternal age, y 163 30.9 ± 5.0 19–44
orrhage without capsule rupture, affected lobule, thrombocytopenia, Gestational age, wk 149 33.2 ± 4.9 18–43
class of HELLP syndrome, eclampsia, blood pressure level, cesarean de- Parity 129 2.1 ± 1.3 1–9
livery, treatment approaches, and maternal and neonatal death. HELLP 1 a 60 34 000 ± 11 000 4000–50 000
HELLP 2 b 74 68 000 ± 16 000 51 000–100 000
Pre-eclampsia was defined as elevated blood pressure (at least 140/
HELLP 3 c 13 116 000 ± 14 000 102 000–150 000
90 mm Hg) with proteinuria (dipstick reading of at least 1+ or at least HELLP NE d 20 — —
0.3 g of protein in a 24-hour specimen) after 20 weeks of pregnancy or Pre-eclampsia/eclampsia without 13 — —
after delivery. Eclampsia was defined as convulsions or seizures during HELLP syndrome
pregnancy or post partum in a woman with pre-eclampsia that could Systolic blood pressure, mm Hg 83 166 ± 27 90–230
Diastolic blood pressure, mm Hg 83 99.8 ± 14 60–130
not be attributed to other causes. The definition of HELLP syndrome
involved the presence of thrombocytopenia (b150 000 cells/μL), hemo- Abbreviation: HELLP, hemolysis, elevated liver enzymes, and low platelet count.
a
Platelet count ≤50 000.
lysis, and hepatic dysfunction (elevated transaminases and lactic dehy- b
Platelet count 50 000–100 000.
drogenase activities). Each case report or series was reviewed for HELLP c
Platelet count 100 000–150 000.
syndrome and HELLP with eclampsia (HEEH). d
Thrombocytopenia and elevated transaminase or hepatic enzymes.
Review of all cases of survival, and maternal and perinatal death
enabled comparison of groups according to occurrence by decade
(1990–2000 versus 2001–2010). The most common techniques used to diagnose hepatic hemor-
The χ 2 and Fisher exact tests were used to analyze qualitative vari- rhage were laparotomy (57 [31.7%]), ultrasound (37 [20.6%]), and
ables. P b 0.05 was considered to be statistically significant. All statis- computed tomography (26 [14.4%]); the method was not reported in
tical analyses were performed using Epi Info version 3.5.3 (Centers 60 (33.3%) cases.
for Disease Control and Prevention, Atlanta, GA, USA). The overall maternal survival rate for cases reported during the
study period (21 years) was 77.8%; however, the total maternal mor-
3. Results tality rate was significantly reduced (43.2%) in the last decade studied
(Table 2). The overall neonatal mortality rate was 30.7%; it remained
The search methodology yielded 116 publications describing cases constant over the study period.
of hepatic hemorrhage with or without capsule rupture associated Various treatment groups were compared for maternal survival
with pre-eclampsia/eclampsia (Fig. 1). (Table 2). Patients who underwent liver transplant or embolization of
In total, 180 cases of hepatic hemorrhage were identified: 18 (10.0%) hepatic artery with/without surgical exploration had the best survival
with subcapsular liver hematoma without hepatic rupture; and 162 rate, ranging from 92% to 100%; the total survival rate was 96.7%
(90.0%) with capsule rupture. Twelve (6.7%) cases were associated (30/31). Surgical exploration without hepatectomy, embolization, and
with HEEH. One (0.6%) case was associated with eclampsia without artery ligation comprised the treatment modality used most (105
HELLP syndrome and 12 (6.7%) cases were associated with pre- [58.3%] cases), with a survival rate of 74.2%. Using this treatment modal-
eclampsia without HELLP syndrome. A total of 167 (92.8%) cases met ity, maternal mortality was significantly reduced to 51.0% during the
the full criteria of HELLP syndrome. last decade. Supportive therapy (blood transfusion and medical support
Average age at time of diagnosis was 30.9 ± 5.0 years; 141/163 without surgery) was used mainly in patients with hepatic hemorrhage
(86.5%) women were older than 25 years of age and 85/163 (52.1%) without hepatic rupture (23 [12.8%]). Hepatic artery ligation was asso-
were aged 28–35 years. Parity was reported in 129 cases; the women ciated with a high rate of survival (10/12 [83.3%]).
were nulliparous in 55 (42.6%) cases (Table 1). Cesarean delivery was
performed in 132/162 (81.5%) cases. The affected lobule was reported 4. Discussion
in 100 (55.5%) cases, with the right lobule (77 [77.0%]) followed by
both lobules (21 [21.0%]) affected most frequently. Spontaneous hepatic rupture in pregnancy is an infrequent but
life-threatening condition that is strongly associated with signifi-
cant maternal and perinatal morbidity/mortality. Furthermore, it is
Records identified from the full search strategy predominantly associated with HELLP syndrome [6–10], with only
(n=207)
a few cases linked to pre-eclampsia/eclampsia without HELLP
syndrome [6,10]. In the present review, hepatic rupture in pre-
eclampsia/eclampsia was associated with HELLP syndrome in 92.8%
Records without new cases of hepatic rupture and pre-eclampsia/eclampsia
(n=79)
of cases. The incidence of hepatic hematoma with or without rupture
is estimated to be approximately 1 case per 53–259 pregnancies com-
plicated by HELLP syndrome [2,9,10]. Accurate and timely diagnosis
Records with full inclusion Full-text article not followed by immediate management of pre-eclampsia/eclampsia
criteria (n=128) located (n=12) and HELLP syndrome contributed to a decreased rate of complications
such as hepatic hematoma. The incidence of spontaneous hepatic
rupture associated with HELLP syndrome can vary between high-
and low-income countries.
Records included in review (n=116) In the present review, the majority of cases of hepatic rupture
180 cases: involved multiparous women (57.4%) over 25 years of age (86.3%);
English (n=86): 123 cases 52.1% of all cases involved women who were 28–35 years of age.
Spanish (n=22): 31 cases These findings are consistent with those from other studies [4,6].
French (n=7): 13 cases
The maternal demographic characteristics in the present and other
Portuguese (n=1): 1 case
studies [4,6] were similar to those reported by Isler et al. [8] in their
study of maternal death as a result of HELLP syndrome. Although
Fig. 1. Flow chart of studies selected for review. pre-eclampsia occurs more often in primigravidae, spontaneous liver
188 P. Vigil-De Gracia, L. Ortega-Paz / International Journal of Gynecology and Obstetrics 118 (2012) 186–189
Table 2
Management and outcome by study period.a
Management
Surgical exploration without hepatectomy, embolization, or artery ligation (n = 105)
Supportive therapy (n = 23)b
Liver transplant (n = 13)
Embolization of hepatic artery with or without surgical exploration (n = 18)
Hepatic artery ligation (n = 12)
Unspecified (n = 9)
Total (n = 180)
a
Values are given as number (percentage).
b
Eighteen cases with hepatic hemorrhage without rupture of capsule.
rupture usually occurs in multigravidae. HELLP syndrome has classi-
cally been defined as a complication of hypertensive disorders of
pregnancy that occurs more often among older multigravidae [8,9],
consistent with the present findings.
Eclampsia occurs 65% of the time in primigravidae with a median
age of 19 years [11–13]. In the present study, only 12 (6.7%) cases of
hepatic hemorrhage were associated with HEEH. Furthermore, only 1
case of eclampsia without HELLP syndrome was found from the past
21 years [14]; however, before HELLP syndrome had been defined,
reports of eclampsia and hepatic rupture were more common [15].
We believe that eclampsia is not an important risk factor for hepatic
hemorrhage/rupture. HELLP syndrome is a true risk and was present
in 92.8% of the cases of hepatic rupture associated with hypertensive
disorders of pregnancy during the past 2 decades. This is an important
point, because the presence of eclampsia did not seem to change the
risk of hepatic hematoma with or without capsule rupture in women
with HELLP syndrome.
Spontaneous hepatic hemorrhage/rupture has been reported to
occur most commonly in the right lobe of the liver [2,16]. This is consis-
tent with findings from the present review, in which the most frequently
affected lobule was the right (77.0%), followed by both lobules (21.0%);
the left lobule was affected in only a small number of cases (2.0%).
Before 1970, the maternal mortality rate associated with hepatic
hemorrhage was up to 100% in cases in which surgical treatment
was not provided [17]. It had decreased to 77% by the early 1980s
[18], and to 39% by the end of the 1990s [4] in cases of surgical man-
agement. In the present review, the maternal mortality rate in cases
of hepatic hemorrhage/rupture during the period 1990–2000 was
28.9%, decreasing to 16.4% during the period 2001–2010. This reduc-
tion probably reflects advances in resuscitation, intensive-care medi-
cine, hepatic surgery, liver transplantation, and arterial embolization—
especially in high-income countries.
Rinehart et al. [7] reported that the perinatal mortality rate in cases
of hepatic hemorrhage/rupture was 78% between 1960 and 1979, de-
creasing to 50% between 1980 and 1997. In the present review, the peri-
natal mortality rate was 30.7%, probably owing to improvements in the
care of preterm and critically ill neonates in the past 2 decades com-
pared with before the 1990s. The perinatal mortality rate remained con-
stant over the past 2 decades.
Accurate and effective management of hepatic rupture is facilitated
by a combination of surgical intervention and aggressive supportive
care. Some surgical techniques have considerably decreased the mor-
bidity and mortality rates associated with hepatic rupture, although
there is not complete agreement on which is the best approach [6]. Con-
servative management [6,19,20], hepatic artery ligation [6,21], arterial
embolization [22,23], hepatorrhaphy [4,5], liver packing [3–6], collagen
sponges [2], absorbable mesh [5], fibrin glue [4], argon laser [2,23], he-
patic transplantation [4,24], recombinant factor VIIa [2,25], and com-
bined management have all been used [2,4,6]. Techniques used in the
management of HELLP syndrome and hepatic rupture vary, especially
between high-income and low-income countries, which can lead to dif-
ferent mortality rates and trends in mortality.
1990–2000 2001–2010 P value
Survival Death Survival Death
37 (66.1) 19 (33.9) 41 (83.4) 8 (16.6) 0.04
8 (80.0) 2 (20.0) 13 (100.0) 00 (0.0) 0.09
4 (80.0) 1 (20.0) 8 (100.0) 00 (0.0) 0.20
5 (100.0) 00 (0.0) 13 (100.0) 00 (0.0) >0.99
4 (100.0) 00 (0.0) 6 (71.4) 2 (28.6) 0.27
1 (33.3) 2 (66.7) 00 (14.2) 6 (85.7) 0.57
59 (71.1) 24 (28.9) 81 (83.6) 16 (16.4) 0.04
In the present review, liver transplantation or the use of selective
arterial embolization by interventional radiologists was associated
with the lowest maternal mortality rate (8.3%). In the last decade stud-
ied, the survival rate was 100% with arterial embolization or liver trans-
plantation. Surgical exploration and management (packing of bleeding
areas, drainage of the perihepatic space, hepatic resection, supportive
therapy, fibrin glue, recombinant factor VIIa, and argon laser) com-
prised the most commonly used treatment modality for managing
women with hepatic rupture and pre-eclampsia/eclampsia in the peri-
od studied. In this treatment group, the maternal mortality rate was
33.9% in the period 1990–2000, decreasing to 16.6% in the period
2001–2010. This reduction was probably associated with advances in
resuscitation and intensive-care medicine.
If there is a clinical suspicion of hepatic hematoma/rupture, radio-
logic evaluation should be performed at the discretion of the physician.
Ultrasound and computed tomography can be used to confirm the diag-
nosis of hepatic subcapsular hematoma before rupture [7]. The ultra-
sound imaging technique is especially useful because it can enable a
bedside diagnosis without having to mobilize the patient away from
specific obstetrics areas, operating rooms, or critical-care areas. How-
ever, when there is clinical suspicion of hepatic rupture, laparotomy
should not be delayed; these patients must be managed in a multi-
disciplinary center with correct management of liver surgery—including
liver transplantation—and experts in arterial embolization. Primary lap-
arotomy and tamponade of the bleeding source should not be post-
poned and must be done in the primary-care hospital if the patient is
not stable enough to be transported [4].
Several hypotheses have been proposed for explaining the devel-
opment of hepatic hemorrhage. We propose that the following se-
quence of events could lead to hepatic hemorrhage and rupture:
hypertension; hypovolemia; vasospasm; hemolysis; fibrin deposition;
platelet aggregation; synusoidal obstruction; ischemia; infarction; ne-
crosis; neovascularization; microhemorrhage; hematoma; and rup-
ture of hepatic capsule [2–7,9,10,17–19,23] (Table 3). Clinicians have
4 clinical conditions for diagnosis and management: pre-eclampsia;
pre-eclampsia with HELLP syndrome; HELLP syndrome with hepatic
hemorrhage or hematoma; and HELLP syndrome with hepatic rup-
ture. The time between pre-eclampsia and hepatic hematoma/rupture
may be hours [2,6,24,25], days [3,20,25], or weeks [5,22]. However,
timely diagnosis of pre-eclampsia/HELLP syndrome and pregnancy
termination can probably prevent progression to hepatic hemorrhage
in some cases. The clinical presentation of pre-eclampsia or HELLP syn-
drome may be atypical; therefore, it could be underrecognized. Further-
more, sudden and massive hepatic rupture can occur without warning
or with symptoms of pre-eclampsia/HELLP syndrome that are not rec-
ognized by women or their families before arrival at hospital.
There were limitations to the present review. First, some cases may
not have been found. Second, only studies published in 4 languages
were considered; however, few cases are published in other languages.
A third limitation was the short study period. However, before 1990,
papers reporting hepatic rupture associated with pre-eclampsia/
eclampsia without mention of HELLP syndrome were common. A
 P. Vigil-De Gracia, L. Ortega-Paz / International Journal of Gynecology and Obstetrics 118 (2012) 186–189 189

Table 3
Sequence of events that could lead to hepatic hemorrhage and rupture.
a
Pathologic finding Signs and symptoms Clinical diagnosis

1 Hypertension, hypovolemia High blood pressure, edema, headache, others Pre-eclampsia

2 Vasospasm where blood flow is increased
3 Microangiopathic hemolysis High bilirubin, schistocytes, high lactate dehydrogenase HELLP syndrome?
4 Fibrin deposition, platelet aggregation (sinusoids) Thrombocytopenia, elevated hepatic enzymes HELLP syndrome
5 Hepatic ischemia, infarction, necrosis Epigastric pain HELLP syndrome
6 Neovascularization
7 Rupture of new vessels, microhemorrhage Several hypertensive episodes, epigastric pain, shoulder pain
b
8 Intrahepatic hemorrhage, subcapsular hematoma Severe epigastric pain, collapse/shock Hepatic hematoma/rupture

Abbreviation: HELLP, hemolysis, elevated liver enzymes, and low platelet count.
a
The signs and symptoms of pre-eclampsia or HELLP syndrome may be atypical in presentation; therefore, they might be underrecognized.
b
Sudden and massive hepatic rupture can occur without warning or with symptoms of pre-eclampsia/HELLP that are not recognized by the women/family before arrival at
hospital.

strength of the present review was that the search methodology was
extensive, comprehensive, and reproducible.
In conclusion, hepatic rupture in pregnancy is strongly associated
with HELLP syndrome; it should be suspected in women who display
a worsening of clinical conditions before, during, or after delivery. He-
patic hemorrhage complicating cases of pre-eclampsia/eclampsia plus
HELLP syndrome was associated with a maternal mortality rate of
16.4% and a perinatal mortality rate of 31.3% during 2001–2010. Thus,
close monitoring is necessary for patients with HELLP syndrome and
those with pre-eclampsia/HELLP syndrome and strong epigastric pain.
Conflict of interest
The authors have no conflicts of interest.
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