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16 Biliary Tract Emergencies
traumatism of the biliary passages during labor.
He quotes Vineberg, who said the great eliminative processes going on at this period, the change
in the intra-abdominal pressure, and the forced
rest in bed with attendant constipation all favor
these attacks.
IUoway, in 1889, reported a case of icterus
gravidarum. The occurrence of jaundice is most
important as its presence affects the uterine contents, and the nearer to the term, the greater the
possibility of exciting labor. Peterson found that
in 15/25 patients, jaundice was present. He stated
that pregnancy could constitutionally produce
jaundice without obstruction by gallstones. The
operative mortality was 13% for 23 cases [31].
The pregnancy seems to have little effect. The
deaths reported were from rupture of the gallbladder, empyema, or extensive or prolonged
operative procedures required by the conditions
found. The occurrence of miscarriage is dependent upon the pathology present more than upon
the effect of the operation. In Peterson’s cases,
two started before the operation and three after.
The latter were cases of severe infection with
chills, fever, and jaundice. Graham reports a case
in the sixth month where the gallbladder ruptured
by a blow to the abdomen. At the operation, three
gallstones were in the abdomen, one in the gallbladder, and two in the cystic duct. He gives
detailed histories of four others operated upon
during pregnancy, all of whom went to term. One
other case refused the operation and died 2years
later from complete CBD obstruction. Regarding
Graham’s paper, Luiz describes a case of gallbladder rupture during labor. The patient died of
general peritonitis, and 250 gallstones were
found scattered through the abdominal cavity
postmortem.
16.1.8.2 Conservative Treatment
Up to 1997, conservative treatment was recommended [22]. Today, uncomplicated symptomatic cholelithiasis is mostly treated nonoperatively
(82–92.5%) [129–131]. The therapy for biliary
colic could be initiated or continued by a primary
care physician after consultation with the gastroenterologist or abdominal surgeon. This recommendation is because even after biliary colic,
there is an increased incidence of premature con-
tractions [130] and even fetal death [132]. The
patients are followed up daily for several days
and then once weekly. Patients with signicant
comorbidities should be hospitalized even for
medical therapy. Traditional indication for medical therapy to delay the cholecystectomy until the
second trimester when the spontaneous abortion
rate after cholecystectomy is the lowest (12% in
the rst trimester and 5.6% in the second trimester) [133], is not recommended. Delay of surgery
until the second trimester may lead to further
complications of gallstone disease such as AC
and biliary AP, risk of maternal malnutrition, and
reduction in fetal growth rate caused by lack of
maternal oral intake leading to higher spontaneous abortion rates and preterm labor (PTL) [107,
134–136]. Also, the PTL and preterm delivery
(PTD) are 0% during the second trimester compared to 40% in the third trimester [133].
The only indication of conservative therapy
of AC is the advanced third trimester.
Cholecystectomy in the third-trimester results in
a longer hospital stay, a higher cost of the cholecystectomy admission episode, and increased
30-day nonobstetric readmissions compared
with women undergoing an operation in the
3months postpartum [137]. However, the risk of
PTD may be associated with antepartum disease
severity and other potential causes for PTD, in
addition to or instead of cholecystectomy timing
[138]. Cholecystectomy during the third trimester is associated with a higher rate of PTD and
overall maternal and fetal complications
[138–142].
Preterm delivery rates are two- to threefold
higher with cholecystectomy performed
during the third trimester than up to
3months postpartum [137, 138, 143, 144].
In patients with complicated gallstone disease
initially presenting during pregnancy with operation delayed to the postpartum period, 35%
recurred within 1 month, and 82% within
3months of delivery [145]. Of those who underwent postpartum LC, up to 78.6% have recurrent
attacks before the operation [129]. On the other
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hand, of those who never had LC, up to 33.3%
have no recurrence of symptoms [129]. Some
patients with conrmed postpartum symptoms do
not undergo LC.This may be due to the preference of recently pregnant patients to avoid disrupting the postpartum period by undergoing an
elective operation. Furthermore, conservatively
treated biliary AP during pregnancy is more
likely to result in postpartum cholecystectomy
[12].
Early LC in the postpartum period is warranted (giving the comfort of a nonpregnant patient) when cholecystectomy is
postponed in advanced pregnancy [145].
Total Parenteral Nutrition
Total parenteral nutrition has been an effective
alternative to the surgical treatment of chronic
cholecystitis in the second and third trimesters
[146], with no adverse effect on maternal weight
gain and fetal growth [147]. The growing fetus
requires essential fatty acids and amino acids to
develop and mature vital organs like the brain
and lungs. Parenteral nutrition provides a viable
means for the fetus to receive these supplements.
A peripherally inserted central catheter (PICC)
carries a lower rate of major complications and
relative ease of insertion than central venous
catheters. PICCs should always be considered,
particularly in high-risk populations like pregnant women, considering a higher rate of minor
complications like thrombophlebitis [148, 149].
PICC insertion is operator-dependent.
Diet
A low-fat diet is essential, minimizing cholesterolrich foods like foods of animal origin, pork, and red
meat, with a slow reduction in body weight and
indulging in more fruits and ber intake. Potent
natural remedies minimize the abnormal concentration of bile acids (acids that help in fat digestion),
keep cholesterol levels in check, heal inammation,
clear out toxins, and eliminate excess lipids.
Beetroot juice is high in ber and has carotenoids
and avonoids that prevent cholesterol from entering the gallbladder and thus stop the formation of
solid pear-shaped gallstones. It has betaine that supports liver function and tames a high sugar level.
Apple juice has a unique compound—malic acid—
that helps soften and disintegrate the gallstones. A
mix of raw juice comprises carrot juice, cucumber
juice, and beetroot juice. The maximum concentration should be carrot juice. Cucumber juice has silica that prevents calcium stones.
Pain Management andAntibiotics
See Chap 2.
Anticholinergic Antispasmodics
Dicyclomine (FDA class B) passes into breast
milk and could affect a nursing infant.
Dicyclomine can suppress the production of
breast milk in nursing mothers.
Ursodeoxycholic Acid
Ursodeoxycholic acid, a naturally occurring bile
acid agent, can dissolve gallstones by changing
the composition of the bile, and it has been used
in nonpregnant patients. Although ursodeoxycholic acid has been administered in pregnancy
to manage ICP, its safety and efcacy for treating
gallstones during pregnancy have not been established [150].
16.1.8.3 Percutaneous Biliary
Drainage
Pregnant patients with recurrent gallbladder colic
during the rst or third trimester or high-risk
patients could be temporarily managed with percutaneous transhepatic gallbladder aspiration
(drainage). Under US guidance and local anesthesia, a pigtail drainage tube is inserted through
the liver and into the distended gallbladder. The
drainage tube should remain until a stula forms
around the tube (≈2weeks). The major disadvantages of this procedure are bile leakage, bile duct
injury, and abdominal abscess. All patients
underwent LC after the procedure. It is used to
postpone the operation until the second trimester
or postpartum when presenting in the third trimester [151, 152]. Although patients delivered
without neonatal complications and subsequently
underwent LC postpartum, insufcient data prevented the recommendation of this approach
[151, 152].
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16 Biliary Tract Emergencies
16.1.8.4 Operative Treatment
General Population
The early operation of AC is recommended in the
general population [153] without an increased
risk of bile duct injury [154, 155]. Early open cholecystectomy (OC), compared to delayed OC, had
the advantages of less blood loss, a shorter operation time, a lower complication rate, and a shorter
hospital stay [46]. Further, laparoscopic cholecystectomy (LC) during the rst admission is associated with a shorter hospital stay, quicker recovery,
and reduced overall cost than OC [154, 155].
According to the updated Tokyo guidelines
[153], the severity of AC has three grades:
• Mild (Grade I): Early LC is the preferred
procedure,
• Moderate (Grade II): Early cholecystectomy
is performed. However, early gallbladder
drainage (percutaneous or surgical) is indicated if patients have severe local
inammation. Because early cholecystectomy
may be difcult, medical treatment and
delayed cholecystectomy are necessary,
• Severe (Grade III): It includes urgent manage-
ment of organ dysfunction and severe local
inammation by gallbladder drainage or cholecystectomy. Delayed elective cholecystectomy should be performed later when
cholecystectomy is indicated.
Pregnant Population
The most common indication for biliary surgery
during pregnancy is repeated biliary colic (37–
70%), followed by AC (20–40%), CBD stones
(7%), and biliary AP in the remaining 3% [22,
135, 156]. Pregnant women with biliary AP are
more likely to be treated surgically compared to
other types of gallbladder disease (32.5% vs.
11.9%) [12].
There are issues in comparing nonoperatively
and operatively managed groups. Nonoperatively
managed group had a more complex obstetric presentation with higher rates of hypertension, preeclampsia, eclampsia, and gestational DM, which
could have predisposed to worse clinical outcomes. However, an operatively managed group
is more likely to present emergently (peritonitis
and sepsis), reecting a higher disease severity.
After accounting for such imbalances using propensity scores, patients treated nonoperatively
still had higher odds of maternal–fetal complications and unplanned readmissions [142, 157].
Recurrence rates after nonoperative treatment
are trimester-dependent, as high as 92% when the
initial presentation is in the rst trimester, 64% in
the second trimester, and 44% in the third trimester [10, 132, 134, 142, 156, 158]. Some claim that
the second trimester has the highest relapse rate,
followed by the rst and third trimesters [130,
159]. An average number of relapses during preg-
nancy is 2–6 [10, 30, 130, 132, 158, 160], each
lasting 5–8days [130]. Also, the disease is often
more severe at relapse [130]. Contrary to current
guidelines, most pregnant women admitted in the
US with AC are managed nonoperatively [157].
Cholecystectomy during the rst trimester
does increase the risk of maternal and fetal complications compared to the second trimester
[139–142]. Others claim that LC can be performed safely in the rst trimester without
increasing maternal or fetal complications, and
there is no need to defer surgery until the second
trimester [161]. The distribution of conservative
and operative treatment across trimesters is presented in Fig.16.6a. The distribution of the type
of abdominal wall access is presented in
Fig. 16.6b. Systematic review conrms that in
advanced pregnancy, conservative treatment is
preferred. If the operation is necessary, LC and
OC are equally frequent (Fig.16.6c).
LC carries a decreased risk of spontaneous
abortion in the rst trimester and premature contractions [133, 163] or PTL [21, 133] in the third
trimester compared to OC.LC is associated with
decreased risks for maternal and surgical complications [162]. Previously, LC was more common
in the puerperium, while OC was during pregnancy [50]. Even in the third trimester, LC is safe
without fetal morbidity [140–142, 164–169].
Today, LC for AC in pregnancy is performed in
>90% in the USA [143, 157], signicantly higher
than two-thirds in the UK [170].
The outcomes of the third trimester should not
be compared to appendectomy outcomes. Acute
appendicitis and AC are distinct pathologies with
different inuences on uterine irritability due to
Y
Percent (%)
Trimester
a
b
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100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
c
First Second Third
Trimester
Cholecystectomy in pregnancy
70
60
50
40
30
20
10
Operative
Nonoperative
p<0.01
Open cholecystectomy
Laparoscopic cholecystectomy
100%
95%
90%
85%
80%
75%
70%
65%
60%
55%
50%
First Second Third
Trimester
PCT
Open CCY
Laparoscopic CC
p<0.35
0
123
Fig. 16.6 (a) Management strategy by trimester among
pregnant patients with acute cholecystitis. (b) Surgical
approach by trimester among pregnant patients with cholecystitis managed operatively. (Reproduced with permis-
different (1) bacteria and localization of peritonitis, (2) distance between inamed organ and
uterus (the appendix is commonly in contact with
the uterus despite trimester), and (3) incidence
and speed of progression to organ perforation.
The maternal and neonatal advantages of
operative treatment are [132] as follows:
sion from [157]). (c) In the third trimester, conservative
treatment is preferred. (Reproduced with permission from
[162]). CCY cholecystectomy, PCT percutaneous cholecystostomy tube
LC was performed at a mean of 5weeks of
gestation earlier than OC, and the serum alkaline
phosphatase was signicantly higher with the
OC.No PTDs occurred after rst-trimester LC
in many studies [21, 168, 169]. LC has signicant advantages in all outcomes compared to OC
(Fig. 16.7). High-volume surgeons have better
outcomes in the pregnant population than low-
• Lower consumption of medications,
• Shorter LOS and number of hospitalizations,
• Lower incidence of life-threatening
volume surgeons (Fig. 16.8). The conversion
rate to OC in pregnancy in Australia is 13%
[171].
complications:
– Perforation,
– Biliary sepsis,
– Peritonitis,
• Lower incidence of biliary AP,
• Lower incidence of spontaneous abortions,
Laparoscopic cholecystectomy is the treat-
ment of choice in the pregnant patient with
gallbladder disease, regardless of the tri-
mester. (SAGES Guidelines 2017 [172])
PTL, and PTD.
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Units
Outcome
Units
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20
16 Biliary Tract Emergencies
Open Laparoscopic
p<.0001
18.9
15
10
5
0
Complications (%)
10.1
Surgical
p<.0001
9.1
3.8
Maternal
Complications (%)
p<.0001
11.3
5.0
Fetal
Complications (%)
p<.0001
6.2
3.7
LOS (mean days) Cost (mean $ in
p<.0001
13.2
9.2
thousands)
Fig. 16.7 Outcomes after cholecystectomy in pregnant women based on the type of procedure. LOS length of stay.
(Reproduced with permission from [143])
Low Volume Surgeon High Volume Surgeon
16
14
12
10
p<.05
12.8
10.3
p<.0001
14.3
p<.0001
9.5
p<.0001
10.4
8.4
8
p<.0001
6
4
3.9
5.0
3.7
2
0
Surgical
Complications (%)
Fig. 16.8 Outcomes after cholecystectomy in pregnant women based on surgeon volume. LOS length of stay.
(Reproduced with permission from [143])
0.9
Maternal
Complications (%)
Fetal
Complications (%)
LOS (mean days) Cost (mean $ in
thousands)
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Contraindications forLaparoscopic Surgery
Contraindications for laparoscopy in pregnancy
are principally the same as in the nonpregnant
population [173]:
Absolute Contraindications
• Hypovolemic shock, massive bleeding, or
hemodynamic instability,
• Severe cardiorespiratory disease,
• Uncontrolled coagulopathy.
Relative Contraindications
• Peritonitis,
• Portal hypertension,
• Multiple previous procedures/extensive intraabdominal adhesions,
• Advanced third trimester.
16.1.8.5 Specic Considerations
Diabetic Pregnant Patient
A single article analyzed a diabetic subgroup of
pregnant patients with symptomatic cholelithiasis.
A total of 35.8% had DM.This is greater than in
the general population of gallstone patients, among
whom DM is 11.1% [174]. This may suggest that
patients with DM have a greater tendency to have
symptomatic gallstones in pregnancy. A more
plausible explanation is that diabetic patients, educated about the tendency of DM to exacerbate the
seriousness of many illnesses and already accustomed to the hospital, sought medical attention
more often than nonpregnant patients. The suggestion is to perform LC during pregnancy in diabetic
patients, even with biliary colic.
IVF Pregnancy
IVF pregnancies are constantly increasing (see
Sect. 15.9.4). Therefore, the number of AC during IVF pregnancy will increase, mainly due to
exposition to higher doses of female hormones, a
known risk factor for the development and progression of biliary sludge and stones. Currently,
there are two cases of LC in IVF pregnancy [175,
176]. There were no intra- or postoperative com-
plications, and the postoperative recovery of
mother and baby was uneventful.
16.1.8.6 Surgical Procedures
Open Cholecystectomy
Two abdominal wall incisions are used in the
nonpregnant population:
• Right subcostal incision,
• Upper midline incision.
The surgical technique for both incisions is
standard, found in any abdominal surgery textbook or atlas. As in any other operation during
pregnancy, it is crucial to avoid or minimize
uterine manipulation to minimize uterine contractions and possible PTL or spontaneous abortion. A laparoscopic [177] or standard clip
applicator shortens the operative time and avoids
uterine retraction. A midline incision is preferred
if CS should be performed due to obstetric
indications.
Laparoscopic Cholecystectomy
For principles of laparoscopy during pregnancy,
see Sect. 3.2.2.2. Pucci and Seed published the
rst case of LC on a 31-week pregnant patient in
1991 [178].
Third Trimester
The previous recommendation was not to perform laparoscopy in the third trimester because
of the risk of uterine injury and the intraoperative
difculties from the enlarged gravid uterus,
which can obstruct safe access to the abdomen
and gallbladder fossa (Fig. 16.9), and the perceived risk for excessive manipulation of the
gravid uterus leading to PTL [180]. A near-term
gravid uterus makes an LC technically impossible, and near-term pregnancy is the only absolute
indication for OC [23, 148]. The specic problem
poses patients with an indication for elective or
emergent CS.After CS, depending on the severity of AC, one can decide between OC and LC
and conservative treatment with elective cholecystectomy after 6weeks.
The upper gestational limit for LC is not
dened—it was set at 26–28weeks [181], while
the increasing number is successfully operated
until 34weeks [140, 168]. The location of trocar
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ladder
Intestine
Fig. 16.9 Enlarged uterus in the advanced third trimester
limits the working space during laparoscopic cholecystectomy [179]
placement should be adjusted according to the
fundal height, earlier incisions, and surgeon’s
experience [182].
Open (Hasson) Technique
Since 2007, the Society of American
Gastrointestinal Endoscopic Surgery (SAGES)
has recommended that the initial access could be
safely accomplished by (1) open (Hasson) technique, (2) Veress needle, or (3) optical trocar.
A Veress needle used for insufation can be
safely inserted in the left (Palmer’s point) or the
right upper quadrant in the midclavicular line,
approximately 1–3cm below the costal margin
[140, 183]. After inserting a 5mm trocar at this
site, a 5mm camera is used to guide the insertion
of the rest of the ports under direct vision [140].
The usual umbilical port for the camera is
placed a few centimeters cephalad from the fundus of the gravid uterus in the midline. In the rst
half of pregnancy, the standard supraumbilical
position is used. The insufation pressure is
12mmHg. A pressure of 15mmHg should not be
of concern in the third trimester [140]. As the
third option, optical trocars can be used with or
without pneumoperitoneum under direct vision.
16 Biliary Tract Emergencies
Fig. 16.10 SIL cholecystectomy with a 10-mm and a
low-prole, 5-mm cannula at the umbilicus. (Reproduced
with permission from [185] under the CC BY 3.0)
Single-Incision Laparoscopic Cholecystectomy
An increasing rate of single-incision laparoscopic cholecystectomy (SILC) in the general
population is translated to the pregnant population [184, 185]. In conventional laparoscopy,
the open (Hasson) technique for intraperitoneal
access is preferred to avoid complications from
the Veress needle insertion. SILC entry is similar to the open technique eliminating the complications of blind Veress needle insertion
[184]. All trocars are located through a transumbilical port eliminating an abdominal wall
and uterine injury through separate stab incisions (Fig.16.10). SILC is used during the rst
and second trimesters. Currently, no recommendations or guidelines for this approach in
pregnancy exist.
Gasless Laparoscopy
See Sect. 3.2.2.2.
The Postpartum Surgery
See Sect. 3.2.2.2.
Intraoperative Cholangiography
Intraoperative cholangiography (IOC) should be
used selectively. It is performed in up to 1/3 of
patients [171]. Alternatives to IOC include intraoperative ductal US or choledochoscopy.
However, their efcacy has not been proven during pregnancy.
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Duration ofHospitalization
LC patients could tolerate clear liquids 0.6days
sooner and regular diet 0.3days sooner than OC
patients [130]. Hospital stay is reduced by half
with LC compared to OC (6 vs. 3) [133, 143,
162]. Mean hospitalization was 2–4.5 days for
AC treated with LC [156, 167] and 3 days for
CBD exploration [156].
16.1.9 Prognosis
16.1.9.1 Maternal Outcome
Despite the type of treatment, gallstone disease is
associated with an increased risk of PTD, maternal and neonatal morbidity (including neonatal
intraventricular hemorrhage and respiratory distress), and hospital readmission [12].
Maternal Mortality
Pregnancy does not seem to increase the severity
of gallstone complications. Most (60–69%) gallstones are asymptomatic during pregnancy [4,
14, 37, 107]. Cholecystectomy in pregnancy does
not increase the risk of maternal mortality [186].
Conservative and operative treatment (AP
excluded) results in maternal mortality of 0%
[12, 156, 187].
Maternal Morbidity
Pregnant women who underwent cholecystectomy compared with not operated pregnant
women hospitalized with biliary tract disease had
signicantly lower maternal complication rates
(4.3% vs. 16.5%) [143]. Following nonoperative
management, the rate of emergent surgery (AC,
biliary AP, acute cholangitis) is 19.5–23% [142,
158]. Compared with nonpregnant women under-
going cholecystectomy, pregnant women had
higher rates of surgical complications and longer
mean length of hospital stay for single hospital
admission [143]. In contrast, others did not nd
any difference [188]. Cumulative length of stay
with several relapses after nonoperative management is several fold compared to LC (see Sect.
16.1.8.4). Most complications include wound
infections [156, 189], while reoperations occur
up to 10% after LC [171]. No signicant differ-
ence in ERCP or intraoperative cholangiogram
rates, the urgency of admission, comorbidity,
income distribution, hospital size, or annual volume of cholecystectomies exists [143].
Obstetric Complications
Compared to surgical treatment, nonoperative
management is associated with a signicantly
higher rate of labor induction and PTD requiring
neonatal intensive care [130], the fetal death rate
[142], and the spontaneous abortion rate [8, 107,
132]. Maternal nutrition could inuence a PTL
(see Sect. 4.3.4). Cesarean section (CS) rate with
conservative treatment is signicantly higher
(35%) than with cholecystectomy [130, 131].
Older studies had a PTL rate of up to 20% after
LC [36, 130, 133, 168, 190]. Currently, it is <5%
[30].
Uterine Injury
See Sect. 16.3.
Gallstone-Related Hospitalization During
theFirst Postpartum Year
Gallbladder disease is a leading nonobstetric
cause of hospitalization in the rst year postpartum. Seventy-six percent were diagnosed with
uncomplicated cholelithiasis, 16% with AP, 9%
with AC, and 8% with cholangitis. Seventy-three
percent of hospitalized women underwent cholecystectomy, and 5% underwent ERCP.Risk factors for hospitalization included maternal race,
age, prepregnancy, overweight or obesity, pregnancy weight gain, and gestational age [7].
16.1.9.2 Fetal Outcome
Earlier studies on pregnancy-related gallbladder
disease showed fetal loss of 12–15% [31, 158,
191], even 24% after a cholecystectomy [192]. At
that time, 10% of pregnancies ended in abortion
[193]. For nonoperative management, the estimated fetal mortality is 7%. Older studies had a
fetal death rate after LC up to 5.2% [36, 130, 133,
168, 190], then lowered to 2.5% [142], and cur-
rently to 0% [30, 156, 171].
The causal relationship to surgery was unclear
because of the varied time lapse between surgery
and abortion. Cholecystectomy in pregnancy
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16 Biliary Tract Emergencies
does not increase the risk of PTL, fetal complication rates, or fetal mortality [143, 169, 186, 187,
189]. LC for the AC has no adverse effects on the
fetal outcome [190, 194, 195]. Excellent cholecystectomy results for biliary colic during the
second trimester of pregnancy [171] conrm that
the underlying disease’s severity, not the procedure itself, inuences the fetal outcome. The progression to AP increases the fetal loss rate (see
Sect. 16.2.7).
The rst-trimester ERCP is associated with a
higher rate of PTD and low birth weight [171,
196].
16.2 Common Bile Duct Stones
andAcute Cholangitis
16.2.1 Incidence
CBD stones complicate 1/1200 pregnancies
[197] and are found in 10–12.5% of pregnant
women undergoing cholecystectomy [159, 198],
and account for 7% of cases of jaundice in pregnancy [9]. In some studies, biliary AP is the most
common form, affecting up to 70% of patients
with AP during pregnancy [199]. The variations
in incidence result from variations in the prevalence of its most common etiologies—gallstone
disease, hypertriglyceridemia, and alcohol consumption. While biliary AP complicated 1/3300
pregnancies in Dallas, Texas [200], in Southern
California, 1/1500 women were affected [199].
nant population. Classic symptoms include
abdominal pain, jaundice, nausea, vomiting, and
itching. Painless icterus without pyrexia indicates
CBD stones or periampullary tumors, while painful icterus with fever and chills points to acute
cholangitis. AC can develop along with CBD
stones.
The abdominal pain (colicky or stabbing) may
radiate to the right ank, scapula, and shoulder.
The onset of pain is rapid, with maximal intensity
in 10–20 min. Pain is steady and moderate to
severe. Band-like radiation of the pain to the back
occurs in 50%. Other symptoms include anorexia,
nausea, vomiting, dyspepsia, low-grade fever,
tachycardia, and fatty food intolerance [200],
some of which cannot be distinguished from
symptoms of AP.Clinical presentation of biliary
AP is similar to AP of any cause (see Chap. 17).
The presentation of gallbladder disease can precede the presentation of biliary AP.
16.2.4 Dierential Diagnosis
Most differential diagnoses could be excluded
with an abdominal US or MRCP.The two entities
in pregnancy are presented in more detail for
easier denitive diagnosis: intrahepatic cholestasis of pregnancy (ICP) and acute fatty liver of
pregnancy (AFLP).
16.2.4.1 Intrahepatic Cholestasis
ofPregnancy
16.2.2 Risk Factors
Due to the small number of these patients in
pregnancy, specic risk factors are unknown. The
etiopathogenesis is the same as in nonpregnant
women. Risk factors are mostly the same as those
for gallbladder stones in pregnancy (see Sect.
16.1.3).
16.2.3 Clinical Presentation
The clinical presentation of pregnant patients
with CBD stones is the same as in the nonpreg-
Incidence andRisk Factors
ICP rarely occurs before 25 weeks and disappears spontaneously after delivery. The prevalence varies widely [201]. The highest frequencies
have been reported in Bolivia and Chile. In Chile,
the prevalence in 1974–1975 ranged from 11.8 to
27.7% according to ethnic origin [202]. For
unknown reasons, the prevalence is decreasing
(4.0–6.5%) [202, 203]. The prevalence ranges
from 0.3 to 5.6% in the USA, according to ethnic
origin [204, 205]. The prevalence in Europe is
0.5–1.5% [201]. ICP is more common in twin
pregnancies [206], in winter months [207], and
following in vitro fertilization treatment (2.7%
vs. 0.7%) [208].
16.2 Common Bile Duct Stones andAcute Cholangitis
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Clinical Presentation
Pruritus is the main symptom, initially on the
palms and soles, progressively spreading to other
body parts and increasingly becoming more persistent. It is more severe at night and disturbs
sleep. Pruritus usually disappears within the rst
few days following delivery [202]. The patient
may also estimate pruritus intensity on the visual
analog scale [209]. These scales for monitoring
pruritus intensity evaluate the effect of medical
treatment on this subjective symptom. The clinical examination ndings are normal, except for
evidence of scratching. Fever, if present, is usually caused by an associated urinary tract infection. The prevalence of jaundice varies from 17 to
75% [210–212]. Some studies may have a greater
frequency of jaundice from concurrent urinary
tract infections [213]. ICP with jaundice but
without pruritus is rare [214]. Patients do not
experience abdominal pain or encephalopathy.
Diagnosis
Patients with ICP frequently exhibit signicant
increases in serum ALT activity, suggesting acute
viral hepatitis, excluded by serologic tests [214].
Liver histology does not reveal necrotic lesions,
and the ALT elevations may be secondary to
increased membrane permeability. The serum
GGT is normal or slightly increased [214]. The
increased serum bile acid concentrations may be
the rst or only laboratory abnormality [214]. A
relationship between maternal serum bile acid
levels and fetal distress has been found, and evaluation of the serum bile acid concentration has
been suggested for fetal assessment in patients
with ICP [209]. However, no consensus has been
reached concerning the usefulness of evaluating
serum bile acid concentrations in the obstetric
management of patients with ICP [215]. Little or
no correlation has been found between the serum
total bile acid concentrations and other liver test
values [214]. The serum bile acid concentration
and serum ALT activity decrease rapidly after
delivery and, as a rule, normalize in a few weeks.
The measurement of serum glutathione
S-transferase, a maker of hepatocellular integrity,
has been proposed to distinguish ICP from
“benign pruritus gravidarum” [216], but its use in
routine is limited. The prothrombin time is usually normal. Abnormal values are found in severe
ICP with jaundice or with cholestyramine treatment. The abnormality is caused by vitamin K
deciency, which should be anticipated and
treated before delivery to prevent hemorrhage.
Such therapy contributes to a good maternal
prognosis. ICP is associated with preeclampsia
[217] or AFLP [218] (see Sect. 16.2.4.2). US
reveals no dilation of the biliary tract but may
show gallstones that are unrelated to ICP.A liver
biopsy is rarely necessary for the diagnosis.
Histopathology is characterized by pure cholestasis, sometimes with bile plugs in the hepatocytes
and canaliculi, predominantly in zone 3.
Inammation and necrosis are not usually
observed, and the portal tracts are unaffected
[219].
Therapy
Apart from elective delivery, drugs used for treatment include ursodeoxycholic acid, dexamethasone, vitamin K, S-adenosyl--methionine, and
cholestyramine.
Prognosis
Most women have no lasting hepatic damage, but
ICP recurs in most cases, with variations in intensity in subsequent pregnancies [206]. There is an
increased risk of gallstones, nonalcoholic cirrhosis and pancreatitis, hepatitis C, and autoimmune
hepatitis [220].
There is a 1–2% increase in the risk of spontaneous PTL, asphyxial events (dened as operative delivery due to asphyxia, Apgar score<7 at
5min, or arterial cord pH <7.05), or meconium
staining of the amniotic uid or placenta and
membranes for every additional μmol/L of maternal serum bile acids [209]. Maternal fasting
serum bile acids <40 μmol/L do not increase
adverse outcomes.
16.2.4.2 Acute Fatty Liver
ofPregnancy
Incidence andRisk Factors
Harold Leeming Sheehan, in 1940, distinguished
AFLP as a specic clinical entity unique to preg-
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