doi:10.1111/j.1447-0756.2011.01726.x J. Obstet. Gynaecol. Res. Vol. 38, No.

2: 446–448, February 2012

Connection between hyperemesis gravidarum, jaundice or

liver dysfunction, and biliary sludge jog_1726 446..448

Shigeki Matsubara1, Tomoyuki Kuwata1, Chihiro Kamozawa1, Yuki Sakamoto1,

Mitsuaki Suzuki1 and Kiichi Tamada2
Departments of 1Obstetrics and Gynecology and 2Gastroenterology, Jichi Medical University, Shimotsuke, Japan

Abstract
Jaundice in hyperemesis gravidarum may cause physicians to suspect several underlying diseases. Jaundice
appeared in a woman with hyperemesis gravidarum and an ultrasound revealed biliary sludge. Hydration
concomitantly ameliorated the symptoms, jaundice and the biliary sludge. Another woman with hyperemesis
gravidarum showed elevated aminotransferases, with biliary sludge also being present. Hydration ameliorated
the symptoms and liver dysfunction, and reduced the total bilirubin level. Biliary sludge appeared, but was
ameliorated according to the symptoms of hyperemesis gravidarum.
Key words: biliary sludge, gallbladder, hyperemesis gravidarum, jaundice, oral feeding.

Introduction 3.9 mg/dL), aspartate aminotransferase (AST) 240 U/L

Although liver dysfunction is sometimes associated
with hyperemesis gravidarum (HG), jaundice is rare.1
Jaundice in HG may cause physicians to suspect an
underlying disease, possibly requiring costly or inva-
sive examinations. Previous reports have showed that
gallbladder biliary sludge, a viscous bile mixture,
is sometimes associated with pregnant women;2,3
however, to our knowledge, no reports have focused
on the association between biliary sludge and HG.
Case Reports
A primiparous Japanese woman suffered nausea, vom-
iting and jaundice during the 12th week of gestation. She
had lost 10.5 kg (75.0 kg → 64.5 kg) over the preceding
five weeks. She had no upper abdominal pain or epigas-
tralgia, her body temperature was 36.8°C, blood pres-
sure 120/74 mmHg and pulse rate 90 bpm. Laboratory
data indicated total bilirubin (TB) 5.2 mg/dL (direct
and alanine aminotransferase (ALT) 518 U/L; and
hepatitis B surface antigen/antibody and hepatitis C
virus antibody were negative. Data suggesting inflam-
mation or infection was absent (white blood cells 7400/
mL, C-reactive protein 0.14 mg/dL). Jaundice made us
suspect underlying diseases, especially of the biliary
tract, and we performed an abdominal ultrasound first
and then an endoscopic retrograde cholangiopancre-
atography (ERCP). The ultrasound revealed a gallblad-
der fully occupied by biliary sludge (Fig. 1a). ERCP
findings were negative. Soon after starting fluid
replacement, the nausea and vomiting ameliorated, and
at hospital day 3, oral feeding began. The serum levels of
bilirubin and AST decreased (TB: 4.7, 1.3, 1.0; AST: 196,
74, 46, on days 2, 5 and 8, respectively). An ultrasound
on day 4 revealed a significant decrease in biliary
sludge (Fig. 1b). The patient went on to have a normal
pregnancy with no further jaundice.
The other patient’s course mimicked that of the
former, but was less typical, thus, its course will be

Received: May 2 2011.

Accepted: July 31 2011.
Reprint request to: Dr Shigeki Matsubara, Department of Obstetrics and Gynecology, Jichi Medical University, 3311-1 Shimotsuke,
Tochigi 329-0498, Japan. Email: matsushi@jichi.ac.jp
Patient anonymity: preserved; informed consent: obtained.

446 © 2012 The Authors

Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology

Figure 1 Abdominal ultrasono-
graphic findings of the gallblad-
der (a) before and (b) after
initiation of oral feeding. (a) The
gallbladder is fully occupied by
diffuse, low-echogenic material
indicative of biliary sludge. The
hyperechogenic area below the
gallbladder indicates the intes-
tines. (b) The amount of biliary
sludge decreased significantly; it
is present only at the bottom of
the gallbladder. No acoustic
shadow is seen, indicating that
it is biliary sludge and not
gallstones.
described more briefly. A primiparous woman was
hospitalized due to HG at the 11th week of gestation.
She had lost 5 kg over three weeks and laboratory data
indicated TB 0.9 mg/dL, AST 77 U/L and ALT
125 U/L. She had no symptoms or findings indicating
inflammation or infection. An ultrasound also revealed
biliary sludge. Fluid replacement ameliorated symp-
toms and liver dysfunction. At the 16th week, the tran-
saminase level became normal (AST 21 U/L, ALT
22 U/L) and the TB level (0.4 mg/dL) decreased, with
a concomitant reduction in biliary sludge.
Discussion
In our patients, gallbladder biliary sludge appeared,
but was ameliorated along with jaundice, liver dys-
function and the severity of HG symptoms. To our
knowledge, this phenomenon has not yet been
reported. These cases suggest three clinical hypotheses;
as the former case appeared to be more typical, the
discussion will therefore be presented with the empha-
sis on the former patient.
First, gallbladder sludge may be associated with the
occurrence of jaundice. Pregnancy itself has been
reported to increase the incidence of sludge.2 HG may
further enhance sludge formation for the following
reasons: first, delayed gastric emptying during preg-
nancy, which is one of the causal factors of HG symp-
toms, may cause sludge formation; second, starvation
due to HG induces Oddi’s sphincter to contract,3,4
causing bile to remain in the gallbladder, leading to
© 2012 The Authors
Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology
Emesis and biliary sludge
sludge formation; third, dehydration due to HG may
condense the bile, also enhancing sludge formation.
Sludge occasionally drops into the cystic/bile duct, dis-
turbing smooth bile drainage and causing jaundice.
Sludge sometimes induces cholecystitis,3 possibly
enhancing jaundice, thus jaundice may appear.
Second, the reduction in HG symptoms may have
assisted the amelioration of biliary sludge and jaundice.
Oral feeding, increasing cholecystokinin secretion,3,4
then decreased the resistance of Oddi’s sphincter,
enhanced the normal hepatic secretion of bile, induced
powerful gallbladder contractions, and finally pushed
the biliary sludge into the duodenum. Hydration,
causing bile to be less viscous, also improved bile drain-
age and the jaundice therefore subsided. We noted
another example of the acute appearance and then dis-
appearance of sludge in a case of total parenteral nutri-
tion. Total parenteral nutrition, with the associated
cessation in oral feeding, induced biliary sludge,3,4
which resolved after reinstitution of oral feeding,5
showing a similar phenomenon observed in this case.
The former patient may be the typical case illustrat-
ing this condition; the latter case may be less typical as
jaundice did not appear. The above-mentioned course
may progress not in an all-or-nothing manner, but as a
continuum of a spectrum. In the latter case, although
jaundice did not appear, a decrease in the TB level and
the amelioration of symptoms, liver dysfunction and
biliary sludge also occurred concomitantly. Thus, the
course of the latter case may also be interpretable in the
same context.
447
S. Matsubara et al.
Third, the concomitant appearance/disappearance
of sludge and jaundice may be a reassuring sign in this
condition. Jaundice may cause physicians to suspect
the presence of a serious disease, thus obliging them to
perform costly or invasive examinations; however, a
decrease in biliary sludge after oral feeding may lessen
the possibility of underlying diseases, and an ERCP
might not be required.
The phenomenon observed here may be explained in
other ways. One possibility is that cholecystitis or a
cholecystitis-related condition induced both HG-like
symptoms (nausea and vomiting) and biliary sludge.
The likelihood of this explanation is low for the follow-
ing two reasons: (i) symptoms or findings of inflam-
mation or infection suggesting cholecystitis were
absent; and (ii) the symptoms occurred at the gesta-
tional weeks in which HG frequently occurs. However,
cholecystitis does not always produce symptoms and
signs, or show serum results indicative of inflamma-
tion, so we cannot therefore preclude this possibility.
Another possibility is that sludge coincidentally
occurred without association with HG. Pregnancy is
considered to be a predisposing factor in biliary sludge
formation.2,3,6 A previous study showed that sludge
was newly formed during pregnancy, and often spon-
taneously disappeared five months postpartum;2
however, the concomitant appearance and disappear-
ance of sludge and HG has not been noted.
A previous study showed that gallstones developed
in 5–15% of patients with biliary sludge over a three-
year follow-up period.6 However, another study
showed that after five months postpartum no gall-
stones developed from newly formed sludge during
pregnancy,2 indicating that such sludge may not be a
risk factor for gallstones during this short period. To
our knowledge, the long-term course of biliary sludge
detected during pregnancy has not yet been studied,
448
Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology
thus it is unclear whether the demonstration of sludge
during pregnancy is a risk factor for future gallstone
development.
In conclusion, HG may accompany biliary sludge,
which might cause jaundice. In HG patients with jaun-
dice, an ultrasound of the gallbladder should be per-
formed, paying special attention to the presence of
biliary sludge. When biliary sludge is observed, its fea-
tures according to HG symptoms should be deter-
mined. Costly or invasive examinations, including an
ERCP or percutaneous transhepatic gallbladder drain-
age, may be avoidable in HG patients with jaundice and
biliary sludge when signs suggestive of biliary tract
obstruction are absent and when sludge subsides con-
comitantly with HG amelioration.
Disclosure
None declared.
References
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© 2012 The Authors