Peer Reviewed CANINE CHRONIC HEPATITIS: DIAGNOSIS & TREATMENT

DIAGNOSIS & TREATMENT

Canine Chronic Hepatitis

Yuri Lawrence, DVM, MA, MS, Diplomate ACVIM
Jörg Steiner, MedVet, DrMedVet, PhD, Diplomate ACVIM & ECVIM
Texas A&M University

Chronic hepatitis is the most common liver

Table 1.
disease in dogs. The World Small Animal Veterinary
Known Causes of Canine Chronic Hepatitis
Association Liver Standardization Group has
published standards for diagnosis of the various CAUsE sPECIFIC EXAMPLEs
forms of chronic hepatitis.1 This article reviews the Drug • Amiodarone
current literature on diagnosis and treatment of • Carprofen
canine chronic hepatitis. • Diethylcarbamazine–
oxibendazole
• Phenobarbital
PROFILE • Trimethoprim/sulfadiazine
Chronic hepatitis is characterized by hepatocellular Infectious Disease • Canine adenovirus type 1
apoptosis or necrosis, a variable mononuclear or • Helicobacter species
mixed inflammatory cell infiltrate, regeneration, and • Herpesvirus
fibrosis on histopathologic examination.1 • Leptospirosis
Clinicopathologic
examination is Genetic Disease/ • Alpha-1-proteinase inhibitor
an important Inherited Defecta deficiency
Predisposition
component of
The Doberman, West Highland white terrier, Other Disease/ • Autoimmune mechanismsb
screening for Condition
Labrador retriever, Skye terrier, American cocker • Copper hepatotoxicosis
evidence of chronic
spaniel, English cocker spaniel, standard poodle, and • Episode of acute hepatitis
hepatitis and
• Various toxicities
concurrent disease, Bedlington terrier breeds are predisposed to chronic
and evaluating the a. Associated with chronic hepatitis in cocker spaniels,
hepatitis.2 but causation—as described in humans—has not been
systemic status of
established in dogs8
the patient. b. Suggested to cause chronic hepatitis in dogs but have
Causes never been confirmed experimentally9
In most cases of canine chronic hepatitis, the cause
is unknown. Known causes are outlined in Table Table 2.
1.3-9 The cause, if known, should precede the term Chronic Hepatitis: Clinical signs & Physical
chronic hepatitis. Examination Findings
CLINICAL PHYsICAL
INITIAL FINDINGS sIGNs EXAMINATIoN
Clinical Signs FINDINGs
Patients with chronic hepatitis often present with
• Abdominal distensiona,b • Ascitesc
nonspecific clinical signs, although more specific • Emesis/diarrhea • Abnormal mucous
signs may occur in patients with advanced disease • Hepatoencephalopathya membrane color
(Table 2). Some affected dogs are asymptomatic at • Hyporexia (due to jaundice)
presentation, and clinical signs may be inapparent in • Jaundice • Abnormal capillary
• Lethargy refill time
patients with compensated advanced disease. • Polydipsia/polyuria (due to hypovolemia)
• Weight loss • Icterus
Physical Examination a. Accompanies advanced disease
Physical examination findings for chronic hepatitis b. Due to ascites from portal hypertension and/or
hypoproteinemia
are nonspecific, often normal and, in most cases, c. Identified as negative prognostic indicator in patients
with chronic hepatitis10,11
do not provide any information to identify the

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 CANINE CHRONIC HEPATITIS: DIAGNOSIS & TREATMENT
affected system unless the patient has jaundice (Table
2). Laboratory investigation is required to further
evaluate patients for chronic hepatitis.
LABORATORY FINDINGS
A complete biochemical profile, complete blood cell
count, and urinalysis are generally adequate to screen
for abnormalities.
Hepatic Abnormalities
Enzyme Activities & Bilirubin. Particular attention
should be given to any elevation of hepatobiliary
enzyme activities and bilirubin:
• Elevated total serum bilirubin concentration has been
identified as a negative prognostic indicator.12
• Increased hepatobiliary enzyme activities, such
as alanine aminotransferase and aspartate
aminotransferase, are consistent with hepatocellular
damage.
• Variable degrees of elevated hepatobiliary enzyme
activities, such as alkaline phosphatase and gamma-
glutamyl transpeptidase, are consistent with
cholestasis.
• Disturbances in markers of hepatocellular damage
often predominate in dogs with chronic hepatitis,
with 90% of patients demonstrating elevated
serum alanine aminotransferase activity.13
Serum hepatobiliary enzyme activities may be
normal, or only mildly increased, in patients with
end-stage chronic hepatitis; therefore, even mild
elevations may be significant, if persistent and when
other potential causes have been excluded. Since dogs
with significant liver disease can be clinically silent,
in those with elevated liver enzyme activities that persist
longer than 4 to 6 weeks, we recommend screening for an
underlying etiology.
There may be additional evidence of hepatic
insufficiency depending on disease severity:
• Decreased serum albumin, cholesterol, blood
urea nitrogen (BUN), glucose (rare), or
hyperbilirubinemia may reflect hepatic insufficiency
or end-stage cirrhotic change.
• These changes must be distinguished from
different or concurrent abnormalities, such as
protein-losing enteropathy, decreased protein
intake, polyuria (increased renal excretion
of BUN), or hemolytic anemia (prehepatic
hyperbilirubinemia).
Liver Function. Specific tests of liver function
are often warranted, but there is no consensus on
which liver function test is most appropriate. The
most commonly performed test in the U.S. and, in
tvpjournal.com | March/April 2015 | TODAY’S VETERINARY PRACTICE
Peer Reviewed
our opinion, the most useful test (in the absence of
hyperbilirubinemia), is the provocative serum total
bile acids test, which includes a fasted preprandial and
2-hour postprandial (provoked) serum total bile acid
concentration.
Other liver function tests include fasted preprandial
serum total bile acid concentration, postprandial
serum total bile acid concentration, and basal plasma
NH3 concentration.
Hematologic Abnormalities
Blood Cells. Nonregenerative anemia due to
decreased mobilization of systemic iron stores
may be present in dogs with chronic hepatitis;
regenerative anemia may be present if associated with
gastrointestinal blood loss. Morphologic erythrocyte
abnormalities due to altered lipoprotein content may
also be seen.
Coagulation. Coagulation status should be
assessed because altered hemostasis can contribute
to clinical disease and may affect diagnostic testing
options. Available tests are listed in Table 3, but no
individual test predicts clinically significant bleeding
and, thus, evaluation of primary and secondary Learn More
hemostasis is recommended. Abnormalities can
Turn to page 87
result from hepatic synthetic failure, vitamin K to read Canine
deficiency, disseminated intravascular coagulation, Leptospirosis:
and qualitative or quantitative platelet defects. (Still) An Emerging
Infection? written by
Serology. Serology for leptospirosis can be Dr. Richard Ford.
submitted to determine the potential role of this
pathogen.
ULTRASONOGRAPHY
Complete abdominal ultrasonography is an essential
component of further diagnostic evaluation
that allows screening for concurrent disease and
acquisition of bile.
• In chronic hepatitis, the liver is variable and can be
normal upon examination.
• Sonographic changes consistent with chronic
hepatitis include uniform increases in liver
Table 3.
Coagulation Tests for Chronic Hepatitis*
• Activated partial thromboplastin time (aPTT)
• Buccal mucosal bleeding time (BMBT)
• D-dimers
• Fibrinogen
• Platelet count
• Prothrombin time (PT)
• Thromboelastography
* The authors frequently evaluate platelet count, PT, aPTT,
and BMBT to evaluate primary and secondary hemostasis.
27
 Peer Reviewed Canine Chronic Hepatitis: Diagnosis & Treatment
FIGURE 1. Laparoscopic-assisted
cholecystocentesis permits safe acquisition of
bile for diagnostic evaluation.
Courtesy Dr. Romy Heilmann, Texas A&M University
echogenicity, decreased distinction of portal vein
margins, and normal to small liver size.
• The liver parenchyma, biliary tree, portal
vein, and peritoneum should be assessed for
abnormalities, acquired shunting, and presence of
free peritoneal fluid.
CHOLECYSTOCENTESIS
Cholecystocentesis to acquire bile for cytologic
evaluation and aerobic/anaerobic bacterial culture and
sensitivity should be routinely performed in patients
suspected of having chronic hepatitis. This technique
can be safely performed via ultrasound guidance,
FIGURE 2. Laparoscopic image of the liver in 7-year-old intact male
Labrador retriever with chronic hepatitis and marked fibrosis. Note
gross discoloration and nodular remodeling.
Courtesy Dr. Romy Heilmann, Texas A&M University
28 Today’s Veterinary Practice | March/April 2015 | tvpjournal.com
laparoscopic guidance, or direct visualization during
laparotomy (Figure 1).
Bacterial cholecystitis can result in clinical signs
and clinicopathologic anomalies indistinguishable
from chronic hepatitis and, thus, exclusion of this
disease is an important component of the diagnostic
evaluation.
DIAGNOSTIC LIVER BIOPSY
Liver biopsy is essential for establishing a definitive
diagnosis in dogs suspected of having chronic hepatitis.
Several biopsy techniques are available for acquiring
histology-grade liver tissue; however, fine-needle
aspiration is NOT adequate for diagnosis of any type
of inflammatory liver disease.
Histopathologic diagnosis of chronic hepatitis
requires demonstration of the characteristic
components: hepatocellular necrosis or apoptosis,
mononuclear or mixed inflammatory cell infiltrate
composed primarily of lymphocytes and plasma cells,
regeneration, and fibrosis.1
• Pattern and distribution of characteristic
components of chronic hepatitis are variable.
• Disease severity is determined by amount of
inflammation present and extent of hepatocellular
necrosis and apoptosis.
• Stage of disease is determined by the extent and
pattern of fibrosis.
• Qualitative increases in copper may be detected
with special stains if levels exceed 400 ppm. The
pattern of copper accumulation can also provide
additional information about the disease process,
with qualitative staining techniques revealing
that:
»» Cholestatic diseases result in periportal (zone 1)
copper accumulation
»» Copper-associated chronic hepatitis results in
centrilobular (zone 3) accumulation.
Percutaneous Ultrasound-Guided Needle Biopsy
Percutaneous ultrasound-guided needle biopsy uses
an automated, semi-automated, or manual biopsy
needle to acquire hepatic tissue. Percutaneous TruCut
(carefusion.com) liver biopsies require ultrasound
guidance and may be limited by a small liver or small
patient size. Particular care should be taken to ensure
adequate sampling (3–6 tissue specimens/samples;
14-gauge for large/medium dogs or 16-gauge for
small dogs).
Advantages include that the technique can be
performed under sedation, is minimally invasive, and
isolated lesions within the hepatic parenchyma can be
 CANINE CHRONIC HEPATITIS: DIAGNOSIS & TREATMENT Peer Reviewed

Wedge Biopsy
Wedge biopsy by laparotomy can be performed
by transfixation or biopsy punch. Advantages and
disadvantages of this technique are similar to those
for laparoscopy. Additional consideration for this
technique is degree of invasiveness; however, it can
be combined with other surgical procedures in the
abdomen.

Other Biopsy Techniques

FIGURE 3. Laparoscopic image of liver after
biopsy; demonstrates normal degree of
postprocedural hemorrhage with normal
coagulation.
A transjugular liver biopsy technique has been
recently described in dog cadavers but due to the
high potential complication rate, which included
perforations of the liver capsule in 13 of 16 dogs
(81%), further studies are needed before this
technique can be recommended.14

specifically sampled. Disadvantages include relatively BIOPSY TECHNIQUE & EVALUATION

smaller biopsy samples and inability to control Biopsy Technique
hemorrhage directly. Sampling may be limited if the All techniques suffer from sampling artifact and, thus,
liver or the patient is of multiple samples should be acquired and multiple
small size.

Laparoscopic Biopsy
Laparoscopic liver biopsy
is performed under general
anesthesia, and the liver
is sampled with biopsy
forceps. Gross examination
of the liver and associated
structures and targeted
sampling of multiple
identified lesions can be A B
performed (Figure 2).
After sample acquisition, the
biopsy sites can be visually
inspected for hemorrhage
(Figure 3).
Advantages of this
technique include direct
visualization of the liver;
relatively large tissue
samples; ability to control
hemorrhage directly with
a palpation probe or a C D
hemostatic agent, such as gel FIGURE 4. Corresponding sections of liver tissue show evidence of severe chronic hepatitis
foam; and access to multiple secondary to excess copper accumulation. Note the different features highlighted by the
liver lobes for sampling. respective stains: (A) hematoxylin–eosin staining highlighting inflammatory infiltrate in
portal triad (arrow), (B) Rhodanine staining highlighting copper granules (arrow), (C) Perls’
Disadvantages include need
iron stain highlighting blue iron granules (arrow), and (D) sirius red staining highlighting red
for specialized equipment
collagen fibrils (arrow) (all images: original magnification, 20×).
and specific skills, general Courtesy Dr. John Cullen, North Carolina State University
anesthesia, and cost.

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 Peer Reviewed Canine Chronic Hepatitis: Diagnosis & Treatment
lobes biopsied. A recent study reported that if the liver
biopsy specimen contains at least 3 to 12 portal triads,
all biopsy techniques carry a similar diagnostic utility.15
Histopathologic Evaluation
Liver tissue samples should be submitted for
histopathologic evaluation (Figure 4, page 29):
• Routine stains include hematoxylin–eosin.
• Special stains to characterize fibrosis or cirrhotic
changes include Sirius red, Masson trichrome stain,
van Gieson stain, and the reticulin stain according
to Gordon and Sweet.1
• Additional stains may also be used to detect certain
substances, such as:
»» Copper (rubeanic acid or rhodanine stain)
»» Iron (Perls’ iron stain)
»» Glycogen (periodic acid–Schiff stain).
Tissue Preparation
Additional special stains, immunohistochemical
techniques, and polymerase chain reaction techniques
can be performed on formalin-fixed tissue but provide
better results in unfixed frozen tissue; therefore, an
additional biopsy specimen should be freshly frozen.
Approximately 1 gram of fresh liver tissue in a
serum blood tube is required for atomic absorption
analysis; however, formalin-fixed tissue may also
be submitted for copper quantification. Copper
Biopsy Coagulation Concerns
Hemorrhage is a risk of all liver biopsy techniques
Concerns & and, thus, assessment of coagulation status is
required despite the relative insensitivity of the
Contra- available coagulation measures for predicting
clinically significant bleeding. Postprocedural
indications monitoring for hemorrhage is advised, with
serial assessment of packed cell volume. Patients
should be kept inactive for 6 to 8 hours after
biopsy collection.
Biopsy Contraindications
Coagulation testing for laboratory analysis should
be performed no more than 24 hours before liver
biopsy because coagulation variables can change
quickly in dogs with chronic hepatitis.
Sampling of the liver is contraindicated if a
severe coagulopathy is present (prolonged
BMBT, platelet count < 80,000, PT/partial
thromboplastin time prolonged > 1.5–2×
normal). In some patients, however, coagulation
measurements can be corrected with vitamin
K supplementation, platelet transfusion,
desmopressin acetate, or administration of fresh
frozen plasma.
30 Today’s Veterinary Practice | March/April 2015 | tvpjournal.com
quantification and aerobic/anaerobic bacterial culture
and sensitivity should be considered a routine part of
the diagnostic evaluation.
THERAPEUTIC APPROACH
The initiating factor in most cases of chronic hepatitis
remains unknown. General principles guiding the
treatment of idiopathic canine chronic hepatitis
include (Table 4):
• Immunosuppressive therapy to resolve or control
the inflammatory process
• Antioxidant therapy to prevent oxidative stress
• Antifibrotic therapy to inhibit fibrosis.
Available evidence suggests that humans
and dogs have similar mechanisms for hepatic
fibrosis in chronic hepatitis; thus, most treatment
recommendations are extrapolated from the human
literature.16,17 Compliance is essential for treatment
success. Therefore, facilitating drug administration
by limiting the number of medications to those most
appropriate is prudent.
Symptomatic Therapy
Treatment of canine chronic hepatitis in most cases
is symptomatic, supportive, and aimed at slowing
progression of fibrosis (Table 4):
• Nausea: Antiemetic therapy
• Gastrointestinal ulceration: Appropriate antacid
therapy
• Portal hypertension: Inhibition of renin-
angiotensin system
• Hepatic encephalopathy: Appropriate dietary,
probiotic, antimicrobial, and lactulose therapy.
Exceptions to limiting treatment to symptomatic
therapy include:
• Copper-associated chronic hepatitis: Specific
treatment includes low-copper diet, copper
chelator, and potentially increased alimentary zinc
• Infection-associated chronic hepatitis: Appropriate
use of antimicrobial agents
• Drug-associated chronic hepatitis: Withdrawal of drug.
Immunosuppressive Therapy
Corticosteroid therapy with prednisone/prednisolone
is the most common immunosuppressive medication
used in dogs with chronic hepatitis. It has been
shown to prolong survival, improve hepatic histologic
changes, and induce remission.18,19 Adjunctive
immunosuppressive therapy, such as leflunomide, can
be added for steroid-sparing effects and/or additional
immunosuppression to achieve disease remission.
In our opinion, remission is best determined by
 Canine Chronic Hepatitis: Diagnosis & Treatment Peer Reviewed

repeat liver biopsy. Serial monitoring every 2 weeks
for normalization or marked reduction of alanine
transaminase activity can be used as a surrogate
marker of disease remission and to indicate repeat
liver biopsy. Glucocorticoids frequently result in
variable increases in alanine transaminase, alkaline
phosphatase, and gamma-glutamyl transpeptidase
activity; therefore, a relative significant decrease or
normalization in alanine transaminase activity is often
used in lieu of a second liver biopsy.
Antioxidant Therapy
The use of antioxidants as an adjunct to standard
therapy is advocated to reduce hepatic injury and
fibrosis in dogs with chronic hepatitis.20
• Studies of human patients with chronic hepatitis

Table 4.
Common Drugs & Nutraceuticals for Management of Canine Chronic Hepatitis
DRUG NAME Dose INDICATION/COMMENTS
Azathioprine 2 mg/kg PO Q 24 H for 10–14 D; then • Anti-inflammatory
Q 48 H • Immunosuppressive (not preferred)
Cyclosporine 5–10 mg/kg PO Q 12 H • Anti-inflammatory
• Immunosuppressive
Lactulose 0.1–0.5 mL/kg PO Q 8–12 H • Decreases ammonia absorption
Leflunomide 4–6 mg/kg PO Q 24 H • Antifibrotic
• Anti-inflammatory
• Immunosuppressive
Losartan 0.25–0.5 mg/kg PO Q 24 H • Antifibrotic
Metronidazole 8–10 mg/kg PO Q 12 H • Anti-inflammatory
• Decreases ammonia-producing bacteria
Mycophenolate 10–12 mg/kg PO Q 24 H • Anti-inflammatory
• Immunosuppressive
Neomycin 22 mg/kg PO Q 8 H • Decreases ammonia-producing bacteria
Omeprazole 1–2 mg/kg PO Q 12 H • Antacid
Penicillamine 10–15 mg/kg PO Q 12 H; administer • Antioxidant
30–60 min before meals • Copper chelator
Prednisone/ 1–2 mg/kg PO Q 24 H until 2–3 weeks • Antifibrotic
prednisolone after clinical remission; then slowly • Anti-inflammatory
taper to lowest effective dose • Immunosuppressive
Probiotic therapy Per labeled instructions • Displaces ammonia-producing bacteria
S-adenosylmethionine 20 mg/kg PO Q 24 H in fasted patient • Antifibrotic
to increase absorption • Anti-inflammatory
Silymarin/silybinin 20–50 mg/kg PO Q 24 H • Antioxidant
Spironolactone 1–2 mg/kg PO Q 12 H • Diuretic for portal hypertension and ascites
Sucralfate 0.5–1 g PO Q 8 H (slurry); administer • Anti-ulcer therapy
at least 2 H before or after all other
medications
Trientine 10–15 mg/kg PO Q 12 H • Copper chelator
(expensive, with few clinical data in dogs)
Ursodeoxycholic acid 10–15 mg/kg PO Q 24 H; dose can be • Anti-inflammatory
divided Q 12 H • Antioxidant
• Choleretic
Vitamin E 250–400 IU/day PO • Antioxidant
Vitamin K 0.5–1.5 mg/kg SC or PO Q 24 H • Deficiency
Zinc (elemental zinc) 10 mg/kg PO Q 12 H • Antifibrotic
• Antioxidant

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 Peer Reviewed CANINE CHRONIC HEPATITIS: DIAGNOSIS & TREATMENT

have documented that those with persistent Protein Restriction

oxidative stress benefit from antioxidant Protein restriction should be limited to the maximum
supplementation.21–24 tolerated level that prevents signs of hepatic
• Glutathione, a potent antioxidant, has encephalopathy; therefore, it may not be appropriate
been reported to be decreased in dogs with to start with the severe protein restriction provided
necroinflammatory liver disease.25 by a prescription liver diet.
• Vitamin E, S-adenosylmethionine, silibinin, If protein restriction is required, diets that contain
N-acetylcysteine, and ursodeoxycholic acid are moderate amounts of protein, such as prescription
antioxidants commonly used as ancillary treatments in renal diets and geriatric diets, may be suitable
dogs with chronic hepatitis. In various studies, these alternatives to a prescription liver diet. Diets may also
nutraceuticals show inhibition of hepatic stellate cell be supplemented with high-quality protein, such as
activation, protection of hepatocytes from apoptosis, egg whites.
and attenuation of experimental liver fibrosis.26-28 A consultation with a board-certified veterinary
• Veterinarians should be aware, however, that nutritionist may be necessary for patients with
limited to no evidence supports the general use comorbid conditions or those in which homemade
of antioxidants in preventing or treating chronic diets are indicated.
hepatitis, and few studies document beneficial
effects of these antioxidants in vivo. Anticopper Therapy
Anticopper drug therapy is generally reserved for
Antifibrotic Therapy cases with documented primary or secondary excess
There is no standard treatment for hepatic fibrosis. copper accumulation.
Experimental studies have identified targets to inhibit • The chelator, penicillamine, is typically used, and
fibrosis in rodents, but the efficacy of most treatments has additional anti-inflammatory and antifibrotic
has not been investigated in dogs.17 Also, the need effects.
to perform serial liver biopsies to accurately assess • Trientine can serve as an alternative if penicillamine
changes in liver fibrosis makes studies documenting is not tolerated.
treatment efficacy difficult. • Copper chelators should be used for 3 to 6 months
The development of reliable noninvasive markers before a second liver biopsy is performed to ensure
for liver fibrosis may enhance the management of adequate disease remission and normalization of
these patients. Drugs with theoretical and limited copper levels; then followed by zinc therapy, if
experimental evidence for the treatment of fibrosis appropriate to prevent copper reaccumulation.
include colchicine, corticosteroids, penicillamine, • Zinc toxicity can result from oral zinc
zinc, angiotensin inhibitors, and angiotensin-receptor administration; periodic monitoring of blood
blockers.13,19,29,30 zinc concentration is recommended with use of
However, the clinical utility of colchicine for the elemental zinc therapy.
reversal or prevention of hepatic fibrosis is limited,
and because of the associated adverse effects, which PROGNOSIS
include vomiting, diarrhea, and inappetance, we do The prognosis for dogs with chronic hepatitis varies.
not recommend routine use of this drug. Median survival durations of 18.3 to 36.4 months
have been reported.
However, patients with
YURI LAWRENCE JÖRG sTEINER hypoalbuminemia,
Yuri Lawrence, DVM, MA, MS, Diplo- Jörg Steiner, MedVet, DrMedVet, PhD, AGAF, hypoglycemia,
mate ACVIM, is enrolled in the Texas Diplomate ACVIM and ECVIM, is a professor in prolonged clotting
A&M University Gastrointestinal PhD the Departments of Small Animal Medicine and
program and also serves as a senior Surgery, and Veterinary Pathobiology, as well as
times, bridging fibrosis,
clinician at the institution’s small animal the director of the Gastrointestinal Laboratory, at and ascites have shorter
hospital. Dr. Lawrence received his DVM
from Tufts University; then completed
Texas A&M University. He was recognized as a survival times.2,11,18,31
Fellow of the American Gastroenterology Asso-
an MA in anatomy and neurobiology at Early diagnosis
Boston University, an internship in small ciation. He received his veterinary degrees from
Ludwig-Maximilians University, Munich, Germa- and intervention are
animal medicine and surgery at North
Carolina State University, and a resi- ny; then completed an internship at University of important for successful
dency in small animal internal medicine Pennsylvania, residency in small animal internal treatment of dogs
and MS in veterinary science at Oregon medicine at Purdue University, and his PhD at
State University. Texas A&M University.
with chronic hepatitis
because patients with

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 Canine Chronic Hepatitis: Diagnosis & Treatment Peer Reviewed

end-stage disease and signs of decompensated liver function prednisolone treatment in canine chronic hepatitis. Vet Q 2013; 33:113-120.
20. Center SA. Chronic liver disease: Current concepts of disease mechanisms. J
have a poorer prognosis. Small Anim Pract 1999; 40:106-114.
21. Chiou YL, Chen YH, Ke T, et al. The effect of increased oxidative stress and
IN SUMMARY ferritin in reducing the effectiveness of therapy in chronic hepatitis C patients.
Clin Biochem 2012; 45:1389-1393.
There is still much unknown about the etiology and treatment 22. Farias MS, Budni P, Ribeiro CM, et al. Antioxidant supplementation attenuates
of chronic hepatitis in dogs. The World Small Animal oxidative stress in chronic hepatitis C patients. Gastroenterol Hepatol 2012;
35:386-394.
Veterinary Association guidelines1 provide an important 23. Yadav D, Hertan HI, Schweitzer P, et al. Serum and liver micronutrient
scaffolding of the etiology and treatment of this disease antioxidants and serum oxidative stress in patients with chronic hepatitis C.
that should build on our current knowledge and facilitate Am J Gastroenterol 2002; 97:2634-2639.
24. Venturini D, Simao AN, Barbosa DS, et al. Increased oxidative stress,
multicenter studies, with the hope of improving patient decreased total antioxidant capacity, and iron overload in untreated patients
survival and outcome. with chronic hepatitis C. Dig Dis Sci 2010; 55:1120-1127.
25. Center SA, Warner KL, Erb HN. Liver glutathione concentrations in dogs and
cats with naturally occurring liver disease. Am J Vet Res 2002; 63:1187-1197.
aPTT = activated partial thromboplastin time; BMBT = 26. Friedman SL, Roll FJ, Boyles J, et al. Hepatic lipocytes: The principal
buccal mucosal bleeding time; BUN = blood urea nitrogen; collagen-producing cells of normal rat liver. Proc Natl Acad Sci USA 1985;
82:8681-8685.
PT = prothrombin time 27. Center SA. Metabolic, antioxidant, nutraceutical, probiotic, and herbal therapies
relating to the management of hepatobiliary disorders. Vet Clin North Am Small
Anim Pract 2004; 34:67-172.
References
28. Webster CR, Cooper J. Therapeutic use of cytoprotective agents in canine
1. Routhuizen J, World Small Animal Veterinary Association, Liver
and feline hepatobiliary disease. Vet Clin North Am Small Anim Pract 2009;
Standardization Group, et al. WSAVA Standards for Clinical and Histological
39(3):631-652.
Diagnosis of Canine and Feline Liver Disease. Edinburgh, New York: Saunders
29. Watson PJ. Chronic hepatitis in dogs: A review of current understanding of the
Elsevier, 2006.
aetiology, progression, and treatment. Vet J 2004; 167:228-241.
2. Poldervaart JH, Favier RP, Penning LC, et al. Primary hepatitis in dogs: A
30. Lubel JS, Herath CB, Burrell LM, et al. Liver disease and the renin-angiotensin
retrospective review (2002-2006). J Vet Intern Med 2009; 23:72-80.
system: Recent discoveries and clinical implications. J Gastroenterol Hepatol
3. Schulze C, Baumgartner W. Nested polymerase chain reaction and in situ
2008; 23:1327-1338.
hybridization for diagnosis of canine herpesvirus infection in puppies. Vet
31. Sevelius E. Diagnosis and prognosis of chronic hepatitis and cirrhosis in dogs.
Pathol 1998; 35:209-217.
J Small Anim Pract 1995; 36:521-528.
4. Chouinard L, Martineau D, Forget C, et al. Use of polymerase chain reaction
and immunohistochemistry for detection of canine adenovirus type 1 in
formalin-fixed, paraffin-embedded liver of dogs with chronic hepatitis or
cirrhosis. J Vet Diagn Invest 1998; 10:320-325.
5. Fox JG, Drolet R, Higgins R, et al. Helicobacter canis isolated from a dog liver
with multifocal necrotizing hepatitis. J Clin Microbiol 1996; 34:2479-2482.
6. Bunch SE. Hepatotoxicity associated with pharmacologic agents in dogs and
cats. Vet Clin North Am Small Anim Pract 1993; 23:659-670.
7. Bishop L, Strandberg JD, Adams RJ, et al. Chronic active hepatitis in dogs
associated with leptospires. Am J Vet Res 1979; 40:839-844.
8. Sevelius E, Andersson M, Jonsson L. Hepatic accumulation of alpha-1-
antitrypsin in chronic liver disease in the dog. J Comp Pathol 1994; 111:401-
412.
9. Poitout F, Weiss DJ, Armstrong PJ. Cell-mediated immune responses to liver
membrane protein in canine chronic hepatitis. Vet Immunol Immunopathol
1997; 57:169-178.
10. Favier RP. Idiopathic hepatitis and cirrhosis in dogs. Vet Clin North Am Small
Anim Pract 2009; 39:481-488.
11. Raffan E, McCallum A, Scase TJ, et al. Ascites is a negative prognostic
indicator in chronic hepatitis in dogs. J Vet Intern Med 2009; 23:63-66.
12. Gomez Selgas A, Bexfield N, Scase TJ, et al. Total serum bilirubin as a negative
prognostic factor in idiopathic canine chronic hepatitis. J Vet Diagn Invest
2014; 26:246-251.
13. Center SA. Chronic hepatitis, cirrhosis, breed-specific hepatopathies, copper
storage hepatopathy, suppurative hepatitis, granulomatous hepatitis, and
idiopathic hepatic fibrosis. In Guilford WG, Center SA, Strombeck D (eds):
Strombeck’s Small Animal Gastroenterology, 3rd ed. Philadephia: Saunders, 1996.
14. Levien AS, Weisse C, Donovan TA, et al. Assessment of the efficacy and
potential complications of transjugular liver biopsy in canine cadavers. J Vet
Intern Med 2014; 28:338-345.
15. Kemp SD, Zimmerman KL, Panciera DL, et al. A comparison of liver
sampling techniques in dogs. J Vet Intern Med 2014 [epub ahead of print].
16. Boisclair J, Dore M, Beauchamp G, et al. Characterization of the inflammatory
infiltrate in canine chronic hepatitis. Vet Pathol 2001; 38:628-635.
17. Bataller R, Brenner DA. Hepatic stellate cells as a target for the treatment of
liver fibrosis. Semin Liver Dis 2001; 21:437-451.
18. Strombeck DR, Miller LM, Harrold D. Effects of corticosteroid treatment on
survival time in dogs with chronic hepatitis: 151 cases (1977-1985). JAVMA
1988; 193:1109-1113.
19. Favier RP, Poldervaart JH, van den Ingh TS, et al. A retrospective study of oral

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