Page 614 - Small Animal Internal Medicine, 6th Edition

586 PART IV Hepatobiliary and Exocrine Pancreatic Disorders

BOX 36.2 have been identified in woodchucks, ground squirrels, tree
squirrels, and ducks, but attempts to identify hepadnavi-
VetBooks.ir Possible Causes of Breed-Related Liver Disease ruses by polymerase chain reaction (PCR) assay in the liver
of dogs with chronic hepatitis or hepatocellular carcinoma
• Increased susceptibility to infectious causes of chronic
hepatitis and/or chronicity of infection have failed. Hepatitis C virus, a Hepacivirus, is another in-
creasingly common cause of chronic hepatitis in humans.
• Mutation in gene involved in metal storage or The recent discovery of a hepatitis C–like virus in dogs cre-
excretion
• Mutation in gene involved in other metabolic ated excitement with the possibility that this might also be
processes (e.g., protease inhibitor production) associated with canine chronic liver disease (Kapoor et al.,
• Increased susceptibility to toxic hepatitis (e.g., 2011). However, the virus was isolated from the respiratory
impaired detoxification of drugs) tract, and subsequent studies have failed to associate the
• Susceptibility to immune-mediated disease virus with chronic hepatitis in dogs (Bexfield et al., 2013).
Two other viruses have been suggested as a possible cause of
canine chronic hepatitis: canine adenovirus type 1 (CAV-1)
and the search for infectious agents continues. Most cases and canine acidophil cell hepatitis virus. CAV-1 causes acute
therefore remain a nonspecific diagnosis of chronic hepatitis, fulminant hepatitis in immunologically naive dogs but can
and the treatment remains nonspecific and symptomatic. also cause chronic hepatitis experimentally in partially im-
However, in a few notable exceptions, such as copper storage mune dogs. However, its importance in naturally occurring
disease, some cases of granulomatous hepatitis, and toxic chronic hepatitis is unclear, and studies are conflicting. An
hepatitis, the cause may be known and treated specifically. alternative viral cause of canine acute, persistent, and chron-
These are outlined in separate sections of this chapter. ic hepatitis was proposed in Glasgow by Jarrett and O’Neil in
1985 and termed canine acidophil cell hepatitis virus pending
IDIOPATHIC CHRONIC HEPATITIS isolation and identification. The virus appeared to be trans-
missible by subcutaneous (SC) injection of liver homoge-
Potential Etiology nate and serum, and was apparently capable of producing a
The potential causes of canine chronic hepatitis are reviewed chronic hepatitis marked by fibrosis and hepatocyte necrosis
in Webster et al., 2019. Idiopathic chronic hepatitis likely but sparse inflammatory changes (Jarrett and O’Neil, 1985;
represents an unidentified viral, bacterial, or other infec- Jarrett et al., 1987). It was proposed at the time that this was
tion, an unidentified previous toxic event, or, in some cases, the most important cause of hepatitis in Glasgow. However,
immune-mediated disease. However, because criteria for there have been no further published studies by these or
diagnosis of immune-mediated chronic hepatitis have not other workers regarding the identity or significance of this
yet been agreed in dogs, immunosuppressive drugs should virus, so its identity and role remain unknown.
be used only cautiously when other potential causes have Bacterial infections have been sporadically reported as
been ruled out as much as possible and the histology is a cause of canine chronic hepatitis, but their importance is
suggestive of an immune-mediated disease. It is also very unclear. Bile-tolerant Helicobacter spp. can cause hepatitis
important to rule out primary or secondary copper buildup centered on the bile ducts in rodents; there was one report
in all dogs with chronic hepatitis by staining liver biopsies for of necrotizing hepatitis associated with Helicobacter canis
copper (see later). More details of when to suspect immune- infection in a pup (Fox et al., 1996). However, no further
mediated hepatitis are described in later sections (“Granulo- work has been reported in dogs, and a clear association
matous Hepatitis” and “Infectious Causes of Canine Chronic between Helicobacter infection and liver disease has yet to
Hepatitis”). be demonstrated.
Primary chronic hepatitis caused by infectious agents is Leptospiral infections may be a clinically relevant and
uncommon in dogs, although there may be a yet-unidentified underestimated cause of chronic hepatitis in dogs. Most
infectious cause in some dogs with what appears to be idio- dogs in the United States are vaccinated regularly against
pathic chronic hepatitis. Clinicians should keep this pos- Leptospira interrogans serovars canicola and icterohaem-
sibility in mind before prescribing immunosuppressive orrhagiae (bivalent vaccine), and the new quadrivalent
medication. Granulomatous hepatitis is an uncommon his- vaccine also protects against L. interrogans serogroup Aus-
tologic diagnosis in which there is a prominent histiocytic tralis serovar Bratislava and L.kirschneri serogroup Grippo-
component to the inflammatory infiltrate. This is usually typhosa serovar Bananal/Lianguang, so it is assumed that
associated with either a foreign body-type reaction to leptospiral infection is now a rare disease. However, recent
increased copper in the liver or a chronic infectious cause, studies have shown an emergence of diseases associated
which should trigger a search for these potential etiologies. with both vaccinal and other serovars; in addition, there is
To date, there has been no convincing demonstration of a little immunologic cross-reaction with the vaccine serovars.
viral cause of canine chronic hepatitis, although it has been Typically, acute leptospiral infections cause both liver and
suspected in several cases. The most common viral cause kidney disease. However, more chronic infections can cause
of chronic hepatitis in people is hepatitis B virus, a hepad- chronic hepatitis alone. Infection with predominantly vacci-
navirus. Similar hepadnaviruses associated with hepatitis nal serovars was recently reported in a case series of 10 dogs