Increased Liver Enzyme Activity in a Dog

1. Jonathan A. Lidbury, BVMS, MRCVS, &
Jörg M. Steiner, DrMedVet, PhD,
Diplomate ACVIM & ECVIM
(Companion Animal)
Texas A&M University
W h a t ’s t h e Ta k e - H o m e ? H E PATO L O G Y
Peer Reviewed
Increased Liver Enzyme Activity
in a Dog
Based on the history, physical examination, and
laboratory and diagnostic imaging findings, which
of the following would be your next step?
A. No further diagnostics at this time, but repeat a
serum biochemical profile in 2 months
A 9-year-old neutered male Labrador retriever
B. Measure pre- and postprandial serum bile acid
concentrations
was referred for increased serum alanine
C. Test for leptospirosis, hyperadrenocorticism,
and hypothyroidism
aminotransferase (ALT) activity.
D. Perform a hepatic biopsy
E. Start treatment with hepatoprotectants and a
commercial “hepatic support” diet
History. The increased ALT activity (4 times the upper limit of the refer-
ence interval) was noticed incidentally by the dog’s primary care veterinarian
4 weeks earlier. A repeat serum biochemical profile obtained 2 weeks ago
showed a similar elevation in ALT activity. The owner reported that the dog
was not displaying any clinical signs of disease. Other than heartworm pre-
ventive, the dog was not receiving any medications and had no known expo-
sure to toxins.
ASK YOURSELF ...
ALT = alanine aminotransferase
22 ...........................................................................................................................................................NAVC Clinician’s Brief / August 2010 / What’s the Take-Home?

2. Glucose (mg/dL) 106 60–135
Cholesterol (mg/dL) 242 120–247
BUN (mg/dL) 13 5–29
Creatinine (mg/dL) 0.9 0.3–2
Magnesium (mg/dL) 1.8 1.7–2.1
Physical Examination. The patient was showed an ALT activity of 584 U/L
judged to be overweight (body condition (reference interval, 10–130 U/L). Urinal-
Total calcium (mg/dL) 9.9 9.3–11.8
score of 7/9). Moderate dental calculus ysis results were within normal limits.
Phosphate (mg/dL) 3.7 2.9–6.2
was noted on oral examination and bila-
Total protein (g/dL) 6.3 5.7–7.8
terial ceruminous discharge was noted Diagnostic Imaging. An abdominal
on otic examination. No other abnor- ultrasound examination showed gastric
Albumin (g/dL) 2.9 2.4–3.6
malities were found. distension but no other significant find-
Globulin (g/dL) 3.4 1.7–3.8
ings. No changes of the liver or biliary
ALT (U/L) 584 10–130
Laboratory Results. The results of a system were observed.
ALP (U/L) 145 24–147
complete blood count and blood smear
examination were unremarkable. A
GGT (U/L) 9 0–25
serum biochemical profile (Table 1) CONTINUES
Total bilirubin (mmol/L) 0.3 0–0.8
Sodium (mmol/L) 144 139–147
Potassium (mmol/L) 3.9 3.3–4.6
Chloride (mmol/L) 115 107–116
Table 1. Serum Biochemical Profile Results
Variable Result Reference Interval
ALP = serum alkaline phosphatase; ALT = serum alanine aminotransferase; BUN = blood urea
nitrogen; GGT = gamma glutamyltransferase
What’s the Take-Home? / NAVC Clinician’s Brief / August 2010..........................................................................................................................................................23

3. W h a t ’s t h e Ta k e - H o m e ? CONTINUED
• Inflammatory (acute hepatitis, chronic hepatitis, lobular
dissecting hepatitis, copper hepatopathy)
• Neoplasia (primary, metastatic)
CORRECT ANSWER: Diagnostics. Because the liver has a considerable
• Infectious (leptospirosis, infectious canine hepatitis,
D. PERFORM A HEPATIC BIOPSY reserve capacity, patients with liver disease can
toxoplasmosis, Heterobilharzia infection)
have normal liver function test results.2 The
• Trauma (contusions, herniation, torsion)
ALT activity is a marker for hepatocellular dam- results of the dog’s serum biochemical profile did
• Hyperplastic hepatic nodules
age (Table 2). While serum alkaline phosphatase not suggest hepatic insufficiency. Paired pre- and
activity may be increased due to a number of postprandial serum bile acid measurement is sen-
extrahepatic conditions, increased serum ALT sitive and specific for detecting hepatic insuffi-
• Endocrine disease (diabetes mellitus, hyperadrenocorticism,
activity is considered to be a more specific ciency in dogs. However, in this case, serum bile
adrenal hyperplasia)
marker for hepatobiliary disease.1 This patient acid measurement would not have aided in diag-
• Inflammatory (enteritis, pancreatitis, peritonitis, systemic
had ALT activity level greater than 4 times the nosis or therapy selection.
inflammatory response syndrome, sepsis)
upper limit of the reference interval, and this ele-
• Hypoxia (anemia, thromboembolic disease, congestive heart
vation persisted for more than 4 weeks. This Abdominal ultrasound is a useful imaging modal-
failure, circulatory shock)
finding suggested clinically important hepatobil- ity for evaluation of the hepatobiliary system.
• Anaphylaxis
iary disease and warranted further investigation. However, clinicians must recognize that patients
• Metabolic (storage diseases)
may have clinically important hepatic parenchy-
mal disease despite an apparently normal liver
and biliary tract on abdominal ultrasonography.3
• Drug toxicity (barbiturates, carprofen, antimicrobials,
azathioprine, glucocorticoids, griseofulvin, ketoconazole)
Table 2. Causes of Increased Serum ALT
• Toxic (heavy metals, copper, carbon tetrachloride,
Extrahepatic Disease. Because of the liver’s cen-
Activities in Dogs
petrochemicals, mycotoxins, blue-green algae, sago palm)
tral role in metabolism and its unique dual blood
supply, it is often affected by extrahepatic disease.
Primary Hepatopathies Hepatopathies can be the primary disease process
• Severe muscle injury (uncommon)
or can be secondary to extrahepatic disease,
drugs, or toxins.4 The diagnostic and therapeutic
approach for patients with primary and secondary
hepatopathies differs greatly. Based on the signal-
ment, history, physical examination, and clinico-
pathologic findings, there was no evidence that
this dog had extrahepatic disease or exposure to
xenobiotics. Consequently, extensive testing for
Secondary Hepatopathies extrahepatic disease was not indicated.
Hepatic Biopsy. Collection of a hepatic biopsy
was indicated due to the strong suspicion of a
chronic primary hepatopathy. No evidence of a
coagulopathy was found on a coagulation profile
(including prothrombin time and activated partial
thromboplastin time) or a buccal mucosal bleed-
ing time.
Xenobiotic-Related Causes
Seven hepatic wedge biopsies were collected
laparoscopically (Figure 1). Six of these were
submitted for histopathology, and one specimen
was immediately frozen. In addition, bile was
submitted for aerobic and anaerobic culture.
Extrahepatic Sources of ALT The frozen specimen was submitted for copper
ALT = alanine aminotransferase
24 ...........................................................................................................................................................NAVC Clinician’s Brief / August 2010 / What’s the Take-Home?

4. • Depending on magnitude and
duration, increases of serum
ALT activity are clinically
important and warrant further
investigation.*
• Hepatic function tests can be
TX AT A GLANCE
normal in patients with early
quantification by flame atomic absorption Treatment. The patient was switched to
chronic hepatitis.
spectrometry (Colorado State University a commercial hepatic support diet with a • Treatment should be
• Abdominal ultrasound exam-
Veterinary Diagnostic Laboratories; vegetable protein source, restricted cop- started as early as
ination can be unremarkable
possible in the course of
in patients with chronic
dlab.colostate.edu). per content, and increased zinc content.5
chronic hepatitis.
hepatic parenchymal disease.
Supportive treatment with ursodiol and
• Treatment should be
• Increases in serum hepatic
Diagnosis. Histopathologic evaluation of SAMe was initiated. The patient’s
guided by hepatic
enzyme activities can be from
the liver biopsy specimens showed chronic hepatic copper accumulation was treated
histopathology, hepatic
extrahepatic sources (eg,
periportal hepatitis with bridging fibrosis. with D-penicillamine.6
copper quantification, and
alkaline phosphatase can be
Copper-staining showed accumulation of bile/liver culture.
of hepatic or bone origin) or
copper in hepatocytes (Figure 2). The See Aids & Resources, back page, for • Chelating agents and
due to primary or secondary
hepatic copper concentration was 1651 references and suggested reading. reduced dietary copper
hepatopathies.
ppm dry weight (reference interval, intake are the main
• Biopsy is indicated in patients
120–400 ppm). The final diagnosis was treatments for copper-
that are suspected of having
associated chronic
chronic primary hepatopathy.
copper-associated chronic hepatitis.
hepatitis.
• Hepatoprotectants have a
place in the treatment of
copper-associated chronic
hepatitis.
TAKE-HOME MESSAGES • The use of corticosteroids
and other antiinflamma-
* In our opinion, further investigation is
tory drugs in the treatment
warranted when a single ALT activity
determination is greater than 5 times
of copper-associated
the upper limit of the reference inter-
chronic hepatitis is
val, or when multiple determinations
controversial.
1
demonstrate activity greater than 2
• Assessment of the
times the upper limit of the reference
interval for more than 4 weeks.
Laparoscopic view of the liver; patient’s response to
biopsy sites are visible on the
margin of the liver treatment is crucial.
2 Copper-associated chronic hepatitis; this histopathologic section shows
abundant copper granules in the cytoplasm of periportal hepatocytes and
in some hepatocytes Rhodamine stain; original magnification, 40x
SAMe = s-adenosylmethionine
What’s the Take-Home? / NAVC Clinician’s Brief / August 2010...........................................................................................................................................................25