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 Peer Reviewed

affected system unless the patient has jaundice (Table our opinion, the most useful test (in the absence of
2). Laboratory investigation is required to further hyperbilirubinemia), is the provocative serum total
evaluate patients for chronic hepatitis. bile acids test, which includes a fasted preprandial and
2-hour postprandial (provoked) serum total bile acid
LABORATORY FINDINGS concentration.
A complete biochemical profile, complete blood cell Other liver function tests include fasted preprandial
count, and urinalysis are generally adequate to screen serum total bile acid concentration, postprandial
for abnormalities. serum total bile acid concentration, and basal plasma
NH3 concentration.
Hepatic Abnormalities
Enzyme Activities & Bilirubin. Particular attention Hematologic Abnormalities
should be given to any elevation of hepatobiliary Blood Cells. Nonregenerative anemia due to
enzyme activities and bilirubin: decreased mobilization of systemic iron stores
• Elevated total serum bilirubin concentration has been may be present in dogs with chronic hepatitis;
identified as a negative prognostic indicator.12 regenerative anemia may be present if associated with
• Increased hepatobiliary enzyme activities, such gastrointestinal blood loss. Morphologic erythrocyte
as alanine aminotransferase and aspartate abnormalities due to altered lipoprotein content may
aminotransferase, are consistent with hepatocellular also be seen.
damage. Coagulation. Coagulation status should be
• Variable degrees of elevated hepatobiliary enzyme assessed because altered hemostasis can contribute
activities, such as alkaline phosphatase and gamma- to clinical disease and may affect diagnostic testing
glutamyl transpeptidase, are consistent with options. Available tests are listed in Table 3, but no
cholestasis. individual test predicts clinically significant bleeding
• Disturbances in markers of hepatocellular damage and, thus, evaluation of primary and secondary Learn More
often predominate in dogs with chronic hepatitis, hemostasis is recommended. Abnormalities can
Turn to page 87
with 90% of patients demonstrating elevated result from hepatic synthetic failure, vitamin K to read Canine
serum alanine aminotransferase activity.13 deficiency, disseminated intravascular coagulation, Leptospirosis:
and qualitative or quantitative platelet defects. (Still) An Emerging
Serum hepatobiliary enzyme activities may be
Infection? written by
normal, or only mildly increased, in patients with Serology. Serology for leptospirosis can be Dr. Richard Ford.
end-stage chronic hepatitis; therefore, even mild submitted to determine the potential role of this
elevations may be significant, if persistent and when pathogen.
other potential causes have been excluded. Since dogs
with significant liver disease can be clinically silent, ULTRASONOGRAPHY
in those with elevated liver enzyme activities that persist Complete abdominal ultrasonography is an essential
longer than 4 to 6 weeks, we recommend screening for an component of further diagnostic evaluation
underlying etiology. that allows screening for concurrent disease and
There may be additional evidence of hepatic acquisition of bile.
insufficiency depending on disease severity: • In chronic hepatitis, the liver is variable and can be
• Decreased serum albumin, cholesterol, blood normal upon examination.
urea nitrogen (BUN), glucose (rare), or • Sonographic changes consistent with chronic
hyperbilirubinemia may reflect hepatic insufficiency hepatitis include uniform increases in liver
or end-stage cirrhotic change.
• These changes must be distinguished from Table 3.
different or concurrent abnormalities, such as Coagulation Tests for Chronic Hepatitis*
protein-losing enteropathy, decreased protein • Activated partial thromboplastin time (aPTT)
intake, polyuria (increased renal excretion • Buccal mucosal bleeding time (BMBT)
of BUN), or hemolytic anemia (prehepatic • D-dimers
• Fibrinogen
hyperbilirubinemia).
• Platelet count
Liver Function. Specific tests of liver function • Prothrombin time (PT)
are often warranted, but there is no consensus on • Thromboelastography
which liver function test is most appropriate. The * The authors frequently evaluate platelet count, PT, aPTT,
and BMBT to evaluate primary and secondary hemostasis.
most commonly performed test in the U.S. and, in

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 Peer Reviewed Canine Chronic Hepatitis: Diagnosis & Treatment

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
FIGURE 1. Laparoscopic-assisted aspiration is NOT adequate for diagnosis of any type
cholecystocentesis permits safe acquisition of of inflammatory liver disease.
bile for diagnostic evaluation. Histopathologic diagnosis of chronic hepatitis
Courtesy Dr. Romy Heilmann, Texas A&M University requires demonstration of the characteristic
components: hepatocellular necrosis or apoptosis,
echogenicity, decreased distinction of portal vein mononuclear or mixed inflammatory cell infiltrate
margins, and normal to small liver size. composed primarily of lymphocytes and plasma cells,
• The liver parenchyma, biliary tree, portal regeneration, and fibrosis.1
vein, and peritoneum should be assessed for • Pattern and distribution of characteristic
abnormalities, acquired shunting, and presence of components of chronic hepatitis are variable.
free peritoneal fluid. • Disease severity is determined by amount of
inflammation present and extent of hepatocellular
CHOLECYSTOCENTESIS necrosis and apoptosis.
Cholecystocentesis to acquire bile for cytologic • Stage of disease is determined by the extent and
evaluation and aerobic/anaerobic bacterial culture and pattern of fibrosis.
sensitivity should be routinely performed in patients • Qualitative increases in copper may be detected
suspected of having chronic hepatitis. This technique with special stains if levels exceed 400 ppm. The
can be safely performed via ultrasound guidance, 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
FIGURE 2. Laparoscopic image of the liver in 7-year-old intact male small dogs).
Labrador retriever with chronic hepatitis and marked fibrosis. Note
Advantages include that the technique can be
gross discoloration and nodular remodeling.
Courtesy Dr. Romy Heilmann, Texas A&M University
performed under sedation, is minimally invasive, and
isolated lesions within the hepatic parenchyma can be

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 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

A transjugular liver biopsy technique has been
recently described in dog cadavers but due to the
high potential complication rate, which included
FIGURE 3. Laparoscopic image of liver after
biopsy; demonstrates normal degree of perforations of the liver capsule in 13 of 16 dogs
postprocedural hemorrhage with normal (81%), further studies are needed before this
coagulation. 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 quantification and aerobic/anaerobic bacterial culture
biopsy specimen contains at least 3 to 12 portal triads, and sensitivity should be considered a routine part of
all biopsy techniques carry a similar diagnostic utility.15 the diagnostic evaluation.

Histopathologic Evaluation THERAPEUTIC APPROACH

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

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 Canine Chronic Hepatitis: Diagnosis & Treatment Peer Reviewed

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