CONSULTANT ON CALL > GASTROENTEROLOGY / HEPATOLOGY > PEER REVIEWED

Diagnosing Liver Disease

Nick Bexfield, BVetMed, PhD, DSAM, DECVIM-CA, FSB, MRCVS
University of Nottingham

Liver disease is relatively common in small animals,

but the diagnosis can be a challenge.

Profile

n The liver has tremendous functional and structural reserve, and a significant loss of
normal hepatic tissue can occur with minimal or no clinical signs.1
n Because of the liver’s central role in metabolism, it may be secondarily affected by a
disease process elsewhere (eg, hyperadrenocorticism, sepsis, hypoxia).
n Secondary hepatopathies often resolve when the underlying disease is appropriately
treated; it is important to determine if an underlying disease process is present early.

History

*
n The onset of clinical signs is often insidious and usually only occurs once the reserve
capacity of the liver has been exceeded.
n Clinical signs are often non-specific; most frequent signs include depression, lethargy,
★
anorexia, weight loss, polyuria, and polydipsia.
n The clinician should pay attention to subtle waxing and waning GI signs (eg,
decreased appetite, vomiting, diarrhea).
n A
 dditional signs that may be suggestive of liver disease (although still not specific)
include jaundice, ascites, and neurologic signs caused by hepatic encephalopathy (HE).
– Clinical signs of HE are often intermittent and include behavioral changes,
hypersalivation, head pressing, circling, ataxia, temporary blindness, seizures, Jaundice in an English springer
and/or coma. 1 spaniel with liver disease.

Physical Examination
n Findings are typically unremarkable.
n A decrease in body condition score may be noted.
n In dogs, liver size will be normal-to-enlarged with acute disease, normal-to-small
with chronic disease.
n In cats, liver size will be normal-to-enlarged in acute and chronic disease.
n P
 alpable hepatomegaly may be appreciated in dogs and cats with an enlarged liver
n Jaundice occurs in approximately 20% of dogs and 30% -40% of cats with hepatobi-
liary disease, and it often occurs late in the disease process (Figure 1).1
n Ascites may be present; it is more commonly associated with chronic disease.

Laboratory Testing
n Blood tests to assess liver enzymes and liver function are usually the simplest next
steps in the investigation of patients with suspected liver disease.
n Definitive diagnosis cannot be based on results of blood tests alone; these results
should form part of the overall investigation. continues
HE = hepatic encephalopathy
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Chemistry Panels n Albumin animals with congenital porto-

n Liver enzyme activity should be mea- n A
 lbumin is produced in the liver; systemic shunt (PSS).
sured in all patients with suspected hypoalbuminemia is only seen n Bilirubin
liver disease, but these allow no eval- when there is >75% reduction in n H epatic hyperbilirubinemia is
uation of hepatic function. functional hepatic mass.1 associated with impaired hepatic
n In general, liver enzymes (Table) are n Glucose uptake, conjugation, or excretion
sensitive indicators of liver disease or n H ypoglycemia occurs most com- into bile.
injury but are not specific.2 monly in acute fulminant hepatic n I t occurs when severe intrahepatic
n N on-specificity derives from the failure, in small-breed dogs with cholestasis develops and when
susceptibility of the liver to sec- portosystemic shunts, or in end- there is more than a 75% reduc-
ondary or reactive disorders and stage liver failure.2 tion in functional hepatic mass.1
the ability of certain hormones or n Cholesterol n Total bile acids
drugs (eg, corticosteroids) to n C holesterol can be normal, n B aseline (fasting) and 2-hour
induce synthesis and release of increased, or decreased in liver postprandial samples should be
some liver enzymes. disease and is a relatively insensi- collected.
tive marker of liver function. n L evels will be elevated in bile sta-
Tests of Liver Function n Blood urea nitrogen (BUN) sis, reduced hepatic function, and
n Tests are generally non-specific, n B UN is decreased when there is in animals with congenital or
although bile acids and ammonia are >75% reduction in functional acquired PSS.
more specific markers of hepatic hepatic mass.1 n T hey should not be measured in
function. n I t is also commonly decreased in patients with hyperbilirubinemia.

Table. Commonly Measured Liver Enzymes & Interpretation

Enzyme

Alkaline phosphatase • Induced enzyme released from canalicular parts of the biliary tract. Elevation suggests cholestasis.
(ALP) • There are several different isoforms (isoenzymes).
• Elevated in young growing animals and in adult dogs with severe active bone lesions.
• Elevated in dogs (but not cats) with endogenous and exogenous corticosteroid and phenobarbital
administration.
• Half-life is approximately 70 hours in dogs and 6 hours in cats; any elevation in a cat is likely to be
clinically relevant.

Gamma-glutamyl • A membrane-bound enzyme located distally in the biliary tree and induced by cholestasis.
transferase (GGT) • GGT also shows corticosteroid induction; unlike ALP, it has no bone isoenzyme and shows less induction
with phenobarbital administration.
• In dogs, GGT is more specific for liver disease than ALP, but it shows much less sensitivity.
• In cats, GGT is more sensitive but less specific than ALP for hepatobiliary disease.

Alanine aminotransferase • Released because of increased hepatocyte membrane permeability or following hepatocellular necrosis.
(ALT) • Liver-specific.
• Half-life of approximately 2.5 days in dogs and several hours in cats; any elevation in a cat is likely to be
clinically relevant.
• Also increased in a dose-dependent manner by corticosteroids and anticonvulsant drugs.

Aspartate • Hepatocellular enzyme; increased activity represents increased leakage from cells.
aminotransferase (AST) • Not liver specific; also released in patients with skeletal muscle damage.
• In acute liver injury, elevations of AST mirror those of ALT, although the overall values tend not
to be as high.

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 Ultrasonographic image demonstrating a diffusely mottled and Histopathology sample obtained at laparotomy that demonstrates
2 nodular appearing hepatic parenchyma. 3 regenerative nodules (wide arrows) and fibrosis (thin arrows), both
of which are indicative of cirrhosis. Hematoxylin and eosin stain;
40× magnification.

n Ammonia n An inflammatory leukogram may be n I magingmay also identify the

n H
 yperammonemia occurs with present with any inflammatory, presence of any extrahepatic
congenital or acquired PSS and infectious, or neoplastic hepatic condition.
when there is >75% reduction in process. n Abdominal radiography can be used
functional hepatic mass.3 to assess liver size, position, and
n Clotting times Urinalysis shape, and it can evaluate for the
n E
 levated prothrombin time (PT) n A low specific gravity (<1.025) is presence of additional abdominal
and partial thromboplastin time common in chronic liver disease and pathology.
(PTT) are seen when there is more congenital PSS. n Radiography in the presence of asci-
than a 75% reduction in func- n Bilirubinuria is found in animals tes is generally unhelpful because
tional hepatic mass.1 with hyperbilirubinemia; it is non- the fluid obscures abdominal detail.
specific in dogs, but a specific indica- n Venography (via injection of contrast
Hematology tor of liver disease in cats. media into a mesenteric vein) may
n Mild non-regenerative normocytic n Urobilinogen is normally found in be used to assess portal vein
normochromic anemia is frequently urine, but increased amounts are vasculature.
identified in these patients. associated with hyperbilirubinemia. n T his is most useful for the identifi-
n Microcytic and hypochromic anemia n Urate or ammonium biurate crystals cation of congenital PSS.
may be present in patients with con- may be seen in patients with hepatic n Ultrasonography is generally the pre-
genital PSS. disease—particularly congenital PSS. ferred diagnostic imaging modality
n Regenerative anemia may be present for evaluation of the liver, and it is
with GI bleeding. Imaging particularly useful for mococeles.
n Morphologic changes in erythro- n Diagnostic imaging is an important n The normal liver has a homogenous
cytes, namely acanthocytes and/or part of the investigation of an animal echogenicity that is isoechoic to
target cells (ie, codocytes) may with suspected liver disease. slightly hyperechoic to the renal
develop. n Imaging sometimes allows identifica- cortex.
n Thrombocytopenia may occur from tion of a specific cause (eg, congeni- n C hanges in hepatic echogenicity
platelet sequestration or increased tal PSS), but it typically just adds occur in acute and chronic liver
destruction. more to the overall clinical picture. disease (Figure 2).

ALT = alanine aminotransferase, ALP = alkaline phosphatase, AST = aspartate aminotransferase, BUN = blood urea nitrogen, FNA = fine-needle
aspiration, GGT = gamma-glutamyl transferase, PSS = porto-systemic shunt, PT = prothrombin time, PPT = partial thromboplastin time continues

July 2015 • Clinician’s Brief 21

CONSULTANT ON CALL

n Ultrasonographic changes are usu- n H

 owever, FNA has limited diag- laboratory testing and diagnostic
ally not specific for a particular nostic accuracy and is generally imaging: $$$–$$$$
disease. only useful to diagnose hepatic n Relative cost for diagnosis includ-
n T he liver can also appear ultraso- vacuolation or diffuse tumors such ing laboratory testing, diagnostic
nographically normal, even in as lymphoma. imaging, and liver biopsy: $$$$–
severe disease. n Obtaining liver tissue using an $$$$$ n cb
n Ultrasonography is useful for exam- ultrasound-guided automated or
ination of the biliary system, includ- semiautomated cutting-type biopsy Cost Key
ing gallbladder size, contents, and needle or during laparotomy or lapa- $ = up to $100
wall thickness, as well as for the roscopy is acceptable. $$ = $101–$250
intra- and extra-hepatic bile ducts. n Liver tissue should be submitted for $$$ = $251–$500
n Doppler ultrasonography and scintig- histopathologic evaluation (Figure 3, $$$$ = $501–$1000
raphy are used for the identification previous page). $$$$$ = more than $1000
of PSS. n I n addition to standard hematoxy-
lin and eosin, a variety of addi-
Sampling Liver Tissue tional stains can be used, such as References
n Results of clinical pathology and Fouchet’s, Masson’s trichrome, 1. Center SA. Pathophysiology of Liver Disease:
Normal and Abnormal function. In: Guilford
diagnostic imaging typically do not periodic acid-Schiff, Perl’s Prussian
WG, Center SA, Strombeck DR, Williams DA,
provide a definitive diagnosis in Blue iron stain, reticulin, rubeanic Meyer DJ, eds. Strombeck’ s Small Animal Gas-
patients with liver disease, except in acid, and rhodanine. troenterology. Philadelphia, PA: W.B. Saunders
Company;1996:553-632.
patients with congenital PSS. n U nfixed liver tissue can also be
2. Bexfield NH, Watson PJ. Diagnosis of canine
n Obtaining liver tissue is the next step submitted for quantitative copper liver disease. In Practice. 2006;28:444-453.
in the investigation of patients with analysis. Note that formalin-fixed 3. Bexfield NH. Ascites and Hepatic Encephalop-
tissue is not appropriate. athy Therapy for Liver Disease. In: Bonagura
liver disease.
JD, Twedt DC, ed. Kirk’s Current Veterinary
n Many methods are available and n Cholecystocentesis (either percutane- Therapy XV. 1st ed. St. Louis, MO: Elsevier
depend on clinician preference, ously under ultrasound guidance or Science;2014:591-594.

equipment availability, technical directly during laparoscopy or lapa-

skills, type of lesion present, location, rotomy) should be performed in Suggested Readings
Center SA. Diagnostic procedures for evaluation
and the systemic stability of the patients with suspected biliary tract
of hepatic disease. In: Guilford WG, Center SA,
patient. disease. Strombeck DR, Williams DA, Meyer D, eds.
n A minimum database to screen for n Animals should be monitored care- Strombeck’s Small Animal Gastroenterology.
3rd ed—Philadelphia, PA: WB Saunders;
hemostatic dysfunction includes a fully for signs of hemorrhage for ≥12 1996:130-188.
platelet count, PT and PTT, and a hours after sampling liver tissue. Lamb CR, Daniel GB. Diagnostic imaging of dogs
buccal mucosal bleeding time prior with suspected portosystemic shunting.
Comp Cont Educ Pract. 2002;24(8):626-635.
to sampling. Relative Cost
Watson PJ. Diseases of the liver. In: Hall E, Simpson
n Fine-needle aspiration (FNA) cytol- n Relative cost for diagnosis including JW, Williams DA, ed. Manual of Canine and
ogy is minimally invasive, requires laboratory testing: $–$$ Feline Gastroenterology. 2nd ed. Gloucester:
BSAVA publications;2005:240-268.
little equipment, and is relatively safe. n Relative cost for diagnosis including

FNA = fine-needle aspiration, PSS = porto-systemic shunt, PT = prothrombin time, PPT = partial thromboplastin time

22  cliniciansbrief.com • July 2015