Gallbladder sludge on ultrasound is predictive of increased liver enzymes and total bilirubin in cats

Abstract

The purposes of this retrospective study were to assess the prevalence of gallbladder sludge (GBS) in a population of cats presented for abdominal ultrasound in a teaching hospital and to determine its association with increased serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (TB). Gallbladder sludge was detected in 152 (14%) of the cats undergoing abdominal ultrasound between 2004 and 2008. This population was compared to a control group of 32 cats without GBS. Alanine aminotransferase, ALP, and TB mean values were significantly higher in cats with GBS than in controls (P ≤ 0.0005) and odds for increased values in cats with GBS were 4.2 [95% confidence interval (CI): 1.6 to 11.0], 9.5 (95% CI: 2.2 to 41.7), and 4.1 (95% CI: 1.5 to 11.5), respectively (P ≤ 0.007). In conclusion, GBS is an uncommon ultrasonographic finding in cats that is predictive of increased liver enzymes and TB. More studies are needed to establish potential links between GBS and hepatobiliary disease in cats.

Full text

CVJ / VOL 52 / SEPTEMB ER 2011 999
Article
Gallbladder sludge on ultrasound is predictive of increased liver enzymes
and total bilirubin in cats
Nathaniel Harran, Marc-André d’Anjou, Marilyn Dunn, Guy Beauchamp
Abstract — The purposes of this retrospective study were to assess the prevalence of gallbladder sludge (GBS) in
a population of cats presented for abdominal ultrasound in a teaching hospital and to determine its association
with increased serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (TB).
Gallbladder sludge was detected in 152 (14%) of the cats undergoing abdominal ultrasound between 2004 and
2008. This population was compared to a control group of 32 cats without GBS. Alanine aminotransferase, ALP,
and TB mean values were significantly higher in cats with GBS than in controls (P # 0.0005) and odds for increased
values in cats with GBS were 4.2 [95% confidence interval (CI): 1.6 to 11.0], 9.5 (95% CI: 2.2 to 41.7), and
4.1 (95% CI: 1.5 to 11.5), respectively (P # 0.007). In conclusion, GBS is an uncommon ultrasonographic find-
ing in cats that is predictive of increased liver enzymes and TB. More studies are needed to establish potential links
between GBS and hepatobiliary disease in cats.
Résumé — La boue de la vésicule biliaire sur une échographie est prédictive d’enzymes hépatiques et de
bilirubine totale chez les chats. Les buts de cette étude rétrospective étaient d’évaluer la prévalence de boue de
vésicule biliaire (BVB) chez une population de chats présentés pour une échographie abdominale dans un hôpital
d’enseignement et pour déterminer son association avec un taux sérique accru d’alanine aminotransférase (ALT),
d’alkaline phosphatase (ALP) et de bilirubine totale (TB). La boue de la vésicule biliaire a été détectée chez 152
(14 %) des chats subissant une échographie abdominale entre 2004 et 2008. Cette population a été comparée à
un groupe témoin de 32 chats sans BVB. Les valeurs moyennes d’alanine aminotransférase, d’ALP et de TB étaient
significativement supérieures chez les chats sans BVB que dans le groupe témoin (P # 0,0005) et les probabilités
de valeurs supérieures chez les chats avec de la BVB étaient de 4,2 [intervalle de confiance (IC) de 95 % : 1,6 à
11,0], 9,5 (IC de 95 % : 2,2 à 41,7) et 4,1 (IC de 95 % : 1,5 à 11,5), respectivement (P # 0,007). En conclusion,
la BVB est une constatation échographique rare chez les chats qui est prédictive de taux accrus d’enzymes hépatiques
et de TB chez les chats. De nouvelles études sont requises pour établir les liens potentiels entre la BVB et la maladie
hépatobiliaire chez les chats.
(Traduit par Isabelle Vallières)
Can Vet J 2011;52:999–1003
Introduction
Gallbladder sludge (GBS) is defined as precipitated par-
ticulate matter dispersed in a viscous liquid phase within
bile (1). It is occasionally identified in cats during abdominal
ultrasound examinations and appears sonographically as mobile
echoes of variable amplitude without acoustic shadowing that
tend to accumulate in the dependent portion of the gallblad-
der (2) (Figure 1). In humans, GBS is composed of cholesterol
monohydrate crystals or calcium bilirubinate granules and other
calcium salts embedded in mucus in variable proportions (3).
While similar components as well as lipid droplets may contrib-
ute to GBS in dogs and cats (4), its exact composition remains
unknown in small animals.
The Companion Animal Research Group, Département de Sciences Cliniques, Faculté de Médecine Vétérinaire, Université de
Montréal, Saint-Hyacinthe, Québec J2S 7C6.
Address all correspondence to Dr. Nathaniel Harran; e-mail: Nathaniel.Harran@bristol.ac.uk
Dr. Harran’s current address is University of Bristol, Division of Companion Animal Studies, Department of Clinical Veterinary
Science, Langford House, Langford, Bristol BS40 5DU.
An abstract of this work was presented at the annual meeting of the American College of Veterinary Radiology, on October 23,
2009 in Memphis, Tennessee, USA.
Use of this article is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the CVMA
office (hbroughton@cvma-acmv.org) for additional copies or permission to use this material elsewhere.

1000 CVJ / VOL 52 / SEPTEMB ER 2011
ARTICLE
In humans, GBS is rare in the healthy adult population and
uncommon in patients with gastrointestinal disorders, with
respective prevalences of 0.0% to 1.7% (5–7) and 5.1% (8).
Conversely, in dogs GBS represents a frequent finding with a
prevalence of 53% in the healthy population (9).
Many reports in human medicine have shown that GBS can
be causally associated with various diseases such as biliary colic,
acalculous cholecystitis, and acute pancreatitis (1,10–12). It has
been postulated that GBS represents an early stage of cholelithia-
sis (13,14); however, in dogs, GBS is not significantly associated
with hepatobiliary disease (9).
In cats, GBS has been reported with various liver diseases,
particularly those affecting the biliary tract (15,16). Also, it has
been suggested that GBS may be more significant or more likely
associated with disease in cats than in dogs (17–19). However,
the prevalence of GBS in cats and its clinical significance have
not been specifically investigated.
In small animal medicine, serum biochemistry is commonly
used to screen for the presence of hepatobiliary disease, in par-
ticular with the measurement of serum liver enzymes [alkaline
phosphatise (ALP) and alanine aminotransferase (ALT)], bili-
rubinemia and bilirubinuria. Indeed, consistent increases in the
serum concentration of liver enzymes and bilirubin occur after
hepatobiliary injury (20). Furthermore, the pattern of abnor-
malities in liver enzymes in relation to the signalment, history,
physical examination, and serum total bilirubin concentration
can indicate a hepatobiliary disorder (21).
The objectives of this study were to determine the prevalence
of GBS in the population of cats presented for abdominal
ultrasound, to describe the clinical signs and laboratory find-
ings in these cats, and to compare the serum liver enzymes and
bilirubinemia in cats with and without GBS. We hypothesized
that serum liver parameters are significantly increased in cats
with GBS.
Materials and methods
Abdominal ultrasound reports of feline patients presented to
the Teaching Hospital of the Faculté de Médecine Vétérinaire of
the Université de Montréal (FMVUM) between 2004 and 2008
were searched retrospectively to identify cats in which GBS was
recorded. The cats were either referral or first opinion cases and
presented for a wide variety of medical or surgical problems. All
ultrasound examinations were performed by a board-certified
radiologist or a radiology resident using a high-definition ultra-
sound system (ATL HDI 5000, 5–8 MHz convex transducer;
Philips Medical Systems, Bothell, Washington, USA). Archived
images of cats in which GBS was reported were reviewed by
one of the authors (MAD) to confirm the presence of GBS
on high-quality images. Medical records of all cats with GBS
were reviewed, and only cats in which measurement of serum
ALT, ALP, and total bilirubin (TB) had been performed at the
FMVUM laboratory (Beckman Synchron CX5 Delta Clinical
System; GMI, Ramsey, Minnesota, USA) and obtained within
1 wk of the ultrasound examination were included in the study.
In patients that were followed over time, only the data obtained
on initial presentation were considered. Signalment, clinical
signs, and urine analysis were recorded where available. Serum
liver parameters were considered as increased when the values
were above the upper limit of the reference interval determined
by the FMVUM laboratory.
A second search was conducted in the same hospital popula-
tion during the same period of time to randomly identify 32 cats
in which GBS was not recorded in the ultrasound report and in
which serum ALT, ALP, and TB were measured at the FMVUM
laboratory within 1 wk of ultrasound evaluation. A power
analysis revealed that such a number of subjects would be suf-
ficient to reveal significant differences at the 0.05 level 80% of
the times between the 2 groups. Ultrasound images obtained in
these cats were reviewed and considered negative for GBS only
if the GB could be well-visualized and appeared fully anechoic
on recorded images.
Results are presented as number or percentage of cats for
categorical variables and mean 6 standard deviation (s) for age
and weight. Mean values for age (years), weight (kg), ALT, ALP,
and TB were compared between groups of cats using an unequal
variance t-test, which is appropriate given the large but unequal
sample size between the 2 groups. The ratio between observed
values and the upper limit of the reference range provided by our
laboratory was calculated for ALT, ALP, and TB. A ratio greater
Figure 1. Sagittal ultrasound images of the liver and
gallbladder (GB) of 2 cats without (A) and with (B) biliary sludge.
(A) The normal GB appears as a teardrop-shaped structure, with
anechoic bile surrounded by a thin, poorly visualized wall. (B) Cat
with GB sludge (white arrow). The sludge appears as moderately
hyperechoic, non-shadowing sediment in the dependent portion
of the GB. In this cat, the GB wall is hyperechoic and mildly
thickened, presumably the result of cholecystitis.

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than 1 indicates elevated values with respect to the reference
range. A chi-squared test was used to determine the association
between groups and sex or breeds. Logistic regression analysis
was used to determine the odds of increased ALT, ALP, and
TB values (ratio . 1) in cats in which GBS was detected by
ultrasound. Significance level was set at P , 0.05 throughout.
SAS v. 9.1 (SAS Institute, Cary, North Carolina, USA) was used
for statistical analyses.
Results
Gallbladder sludge was detected during ultrasonography in
152 cats (92 males, 60 females), which represented a prevalence
of 14% in our population of cats that underwent complete
abdominal ultrasound during the period (1100 cats). The
signalment of cats with GBS is presented in Table 1. At the
time of admission, cats were presented with decreased appetite/
anorexia (62%), lethargy (55%), weight loss (51%), dehydration
(50%), and vomiting (43%). Other clinical signs are presented
in Table 2.
Most cats with GBS underwent serum biochemistry at the
FMVUM for ALT (106/152), ALP (106/152), TB (102/152),
and bilirubinuria (73/152). All cats had serum values measured
within 1 wk of the ultrasound examination. Values for ALT,
ALP, and TB were above the reference interval in 49%, 38%,
and 44% of cats, respectively (Table 3). Also, bilirubinuria was
above the reference interval in 23% of cats. The median (range)
of ALT, ALP and TB, and the range of ratios with respect to the
upper limit are also presented in Table 3.
The control group consisted of 32 cats without GBS on
ultrasound. The signalment of these cats is presented in Table 1.
Alanine aminotransferase, ALP, and TB were measured in 32,
32, and 31 cats, respectively. The median (range) of ALT, ALP
and TB, and the range of ratios with respect to the upper limit
are presented in Table 3.
Mean age and weight were compared between cats with GBS
and controls. The unequal variance t-test indicated that cats with
GBS (n = 152) were significantly older (P = 0.01) and lighter
(P = 0.03) than controls (n = 32). The chi-squared test showed
no association between group and sex (P = 0.76), and between
group and breeds (P = 0.36).
The unequal variance t-test indicated that mean values were
significantly higher in cats with GBS than in controls for ALT
(P , 0.0001), ALP (P = 0.0002), and TB (P = 0.0005). Logistic
regression indicated that the odds of observing values above
the reference interval were significantly related to the group for
ALT (P = 0.004), ALP (P = 0.003), and TB (P = 0.007). Odds
for increased values for ALT, ALP, and TB were 4.2 [95% con-
fidence interval (CI): 1.6 to 11.0], 9.5 (95% CI: 2.2 to 41.7),
and 4.1 (95% CI: 1.5 to 11.5), respectively, in cats with GBS
in comparison with controls.
Discussion
The results of this study indicate that GBS is an uncommon
sonographic finding in cats, but when present is significantly
associated with increased liver enzymes and total bilirubinemia.
The prevalence of GBS in our population of cats (14%) was
lower than that reported in dogs (9). In that study, GBS was
present in about half of the dogs without hepatobiliary disease
(48% to 53%), with a non-significant tendency to be more
prevalent (62%) when hepatobiliary diseases were identified.
Conversely, GBS is an uncommon ultrasonographic finding in
healthy adult humans (# 1.7%) (5 to 7), increasing somewhat
in prevalence with gastrointestinal disease (5.1%) (8).
In our study, nonspecific clinical signs such as decreased
appetite or anorexia, lethargy, dehydration, weight loss, and
vomiting were commonly recorded. In dogs, it is generally
accepted that GBS is common in anorexic or fasted patients
(4,9). Interestingly, the mean body weight of cats with GBS was
significantly reduced when compared with the control group. It
is possible, therefore, that the GBS in the cats in this study was a
secondary effect of poor appetite, rather than specifically related
to hepatobiliary disease. Also, another significant finding is that
cats with GBS in our study were significantly older when com-
pared to control cats. This is consistent with a previous study
that found GBS to be an age-related phenomenon in dogs (9).
In humans, pregnancy, prolonged fasting, major abdominal
surgery, total parenteral nutrition, weight loss, bone marrow or
solid organ transplantation, octreotide and ceftriaxone treatment
have been associated with GBS. Many reports have shown that
GBS can be causally associated with hepatobiliary disease such
as biliary stasis, abdominal pain due to biliary colic, acalculous
cholecystitis, and acute pancreatitis (1,10–12). In almost all of
Table 1. Signalment of cats with and without gallbladder sludge
Cats with GB sludge Cats without GB sludge
(n = 152) (n = 32)
Mean age (years) 6 s 10.3 6 4.8 8.0 6 4.4
Mean weight (kg) 6 s 4.2 6 1.2 4.9 6 1.7
Breed
Domestic cats 76% 84%
Himalayan 5% 0%
Persian 4% 6%
Siamese 4% 0%
Maine Coon 2% 6%
Abyssinian 0% 4%
Sexual status
Castrated males 57% 50%
Spayed females 35% 41%
Intact females 5% 3%
Intact males 3% 6%
s — standard deviation.
GB — gall bladder.
Table 2. Frequency of clinical signs in cats with gallbladder sludge
Prevalence
Clinical signs (n = 152)
Decreased appetite/anorexia 62%
Lethargy 55%
Weight loss 51%
Dehydration 50%
Vomiting 43%
Heart murmur 36%
Jaundice 19%
Diarrhea 18%
Abdominal pain 16%
Polyuria — polydipsia 13%

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these conditions, impaired GB contractility has been implicated
in the pathogenesis of sludge (12).
As in humans, several studies support the hypothesis that
GBS is a significant sonographic finding in cats. For instance,
the presence of GBS has been associated with cholangiohepatitis
complex (CHC), cholecystitis, and extrahepatic biliary obstruc-
tion (EHBO) in cats (17–19,22). Gallbladder sludge was also
detected in 40% of cats with hepatobiliary or gastrointestinal
disease (16) and in 62% of cats with EHBO (15). These studies
suggest that GBS could be related to the presence of cholestasis
in cats, unlike dogs. Whether cholestasis leads to the inspissa-
tion of bile, producing GBS (17,18), or, the opposite, that GBS
causes bile flow obstruction (22), remains to be determined.
Finally, although GBS and cholelithiasis have been reported
concurrently in cats, a causative association has yet to be con-
firmed (23).
In our study, an elevation in ALT, ALP activity, and TB
was present in nearly half of the population of cats with GBS.
Logistic regression showed that these cats are significantly more
likely to have an elevation of these values when compared to cats
without GBS. Increased ALT activity is a marker of hepatocel-
lular damage and the magnitude of activity seems to correlate
with the number of cells involved (20); thus, ALT elevation
is generally considered to be specific (80%) for hepatobiliary
disease in cats (20). Increased ALP activity generally indicates
cholestasis, particularly in cats (21). Moreover, elevation in
serum ALP in cats is more specific (87%) for hepatobiliary dis-
ease than in dogs (21). Total bilirubin is less sensitive than serum
liver enzyme measurement for the detection of hepatobiliary
disease; however, its elevation is considered more specific (20).
Our results show that GBS is related to increased serum liver
enzymes and total bilirubin and indirectly suggest that GBS is
most likely to be specifically linked to hepatobiliary disease.
Some limitations of this study result from its retrospective
design, in that additional cats which had GBS were not recorded
in the ultrasound report, may have lead to an underestimation
of the true prevalence of this sonographic finding in our hospital
population. Only isolated serum liver enzymes and TB values
were considered. It would be preferable to study the course of
these parameters over time. Another important limitation is that
histological analysis of the liver parenchyma, pancreas, and bili-
ary tract was not performed in most cats, precluding determina-
tion of a relationship between the presence of GBS and potential
hepatobiliary pathology. Finally, other sonographic findings such
as liver changes in echogenicity, echotexture and size, biliary
abnormalities such as cholelithiasis and wall thickening, and
pancreatic and gastrointestinal changes were not considered in
this study, mainly because of the inconsistency of description
and grading of these parameters in ultrasound reports, and the
difficulty in assessing those features retrospectively using still
ultrasound images.
In conclusion, our study showed that GBS in cats is an
uncommon ultrasonographic finding and that cats with GBS are
more likely to have elevated serum ALT, ALP, and TB. Hence,
GBS in cats appears to be a significant sonographic finding that
may predict hepatobiliary disease; this contrasts with findings
in dogs. These results justify prospective studies correlating
GBS with histological diagnosis as well as other sonographic
features of hepatobiliary disease to better determine its clinical
significance.
Acknowledgments
The authors thank the radiologists and imaging residents of the
FMVUM Teaching Hospital and the pathologists and residents
of the Service de Diagnostic of the same institution, in particular
Dr. Benoit Rannou. CVJ
References
1. Shaffer EA. Gallbladder sludge: What is its clinical significance? Curr
Gastroenterol Rep 2001;3:166–173.
2. Filly RA, Allen B, Minton MJ, Bernhoft R, Way LW. In vitro investiga-
tion of the origin of echoes with biliary sludge. J Clin Ultrasound 1980;
8:193–200.
3. Lee SP, Nicholls JF. Nature and composition of biliary sludge. Gastro-
enterology 1986;90:677–686.
4. Center SA. Diseases of the gallbladder and biliary tree. Vet Clin North
Am Small Anim Pract 2009;39:543–598.
5. Angelico M, De Santis A, Capocaccia L. Biliary sludge: A critical update.
J Clin Gastroenterol 1990;12:656–662.
Table 3. Liver enzymes and total serum bilirubin in cats with and without gallbladder
sludge
ALT ALP TB
Units U/L U/L mmol/L
Cats with GBS
N 106 106 102
Median (range) 62 (7–1044) 32 (2–2144) 9 (4–305)
Reference interval 16–63 0–50 0–10
Frequency of increased values 49% 38% 44%
Range of values in relation to the
upper limit of the reference interval 0.1–16.6 0.0–42.9 0.4–30.5
Cats without GBS
N 32 32 31
Median (range) 46 (16–142) 20 (2–58) 7 (2–75)
Reference interval 16–63 0–50 0–10
Frequency of increased values 19% 6% 16%
Range of values in relation to the
upper limit of the reference interval 0.3–2.3 0–1.2 0.2–7.5
ALT — alanine aminotransferase; ALP — alkaline phosphatase; TB — total bilirubin; GBS — gallbladder
sludge.

CVJ / VOL 52 / SEPTEMB ER 2011 1003
ARTICLE
6. Janowitz P, Kratzer W, Zemmler T, Tudyka J, Wechsler JG. Gallbladder
sludge: Spontaneous course and incidence of complications in patients
without stones. Hepatology 1994;20:291–294.
7. Jorgensen T. Prevalence of gallstones in a Danish population. Am J
Epidemiol 1987;126:912–921.
8. Boscaini M, Magnani G, Mandetta S, Montori A. Morphological
appearance of low-level echoes in the gallbladder. Interpretation with
microscopic biliary analysis and clinical correlation. Surg Endosc 1987;
1:41–49.
9. Bromel C, Barthez PY, Leveille R, Scrivani PV. Prevalence of gallbladder
sludge in dogs as assessed by ultrasonography. Vet Radiol Ultrasound
1998;39:206–210.
10. Jungst C, Kullak-Ublick GA, Jungst D. Gallstone disease: Microlithiasis
and sludge. Best Pract Res Clin Gastroenterol 2006;20:1053–1062.
11. Ko CW, Sekijima JH, Lee SP. Biliary sludge. Ann Intern Med 1999;
130:301–311.
12. Pazzi P, Gamberini S, Buldrini P, Gullini S. Biliary sludge: The sluggish
gallbladder. Dig Liver Dis 2003;35:39–45.
13. de la Porte PL, Lafont H, Domingo N, et al. Composition immuno-
fluorescence studies of biliary «sludge» in patients with cholesterol or
mixed gallstones. J Hepatol 2000;33:352–360.
14. Jungst D, Del Pozo R, Christoph S, et al. Sedimentation of biliary
sludge: Effect on composition of gallbladder bile from patients with
cholesterol, mixed, or pigment stones. Scand J Gastroenterol 1996;31:
273–278.
15. Gaillot HA, Penninck DG, Webster CR, Crawford S. Ultrasonographic
features of extrahepatic biliary obstruction in 30 cats. Vet Radiol
Ultrasound 2007;48:439–447.
16. Hittmair KM, Vielgrader HD, Loupal G. Ultrasonographic evalu-
ation of gallbladder wall thickness in cats. Vet Radiol Ultrasound
2001;42:149–155.
17. Day DG. Feline cholangiohepatitis complex. Vet Clin North Am Small
Anim Pract 1995;25:375–385.
18. Penninck D, Berry C. Liver imaging in the cat. Semin Vet Med Surg
(Small Anim) 1997;12:10–21.
19. Zawie DA, Garvey MS. Feline hepatic disease. Vet Clin North Am Small
Anim Pract 1984;14:1201–1230.
20. Webster CR. Liver and pancreatic diseases — Laboratory evaluation
of hepatobilary diseases. In: Ettinger JS, Feldmann EC, eds. Textbook
of Veterinary Internal Medicine. 6th ed. Philadelphia, Pennsylvania:
WB Saunders, 2005:1421–1430.
21. Center SA. Interpretation of liver enzymes. Vet Clin North Am Small
Anim Pract 2007;37:297–333.
22. Gaschen L. Update on hepatobiliary imaging. Vet Clin North Am Small
Anim Pract 2009;39:439–467.
23. Mayhew PD, Holt DE, McLear RC, Washabau RJ. Pathogenesis and
outcome of extrahepatic biliary obstruction in cats. J Small Anim Pract
2002;43:247–253.