Page 644 - Small Animal Internal Medicine, 6th Edition

616 PART IV Hepatobiliary and Exocrine Pancreatic Disorders

SECONDARY HEPATOPATHIES

VetBooks.ir Secondary (reactive and vacuolar) hepatopathies are
common in dogs. In pathology studies it is clear that they
are more common than primary hepatic disease. Many of
these hepatopathies result in elevations in liver enzyme
activities, but usually the liver changes are not clinically rel-
evant and do not result in compromised liver function.
However, they are often confused with primary liver disease,
and it is important to rule out secondary hepatopathies as
much as possible in the workup of dogs with elevated liver
enzyme activities to allow identification and treatment of the
underlying primary disease (e.g., endocrine disease or
inflammatory disease elsewhere in the splanchnic bed). High
liver enzyme activities in older dogs have many other causes
in addition to primary liver disease, and it is also important
FIG 36.17 to resist the urge to put them on a protein-restricted diet and
Ultrasonographic appearance of the liver of a 6-year-old other medications for liver disease before working up the
Border Terrier with hepatocutaneous syndrome secondary to case properly. Many dogs with secondary hepatopathies will
chronic phenobarbital medication for idiopathic epilepsy.
Note the typical hypoechoic holes in the liver parenchyma not have hepatic histopathology performed because the
on the left. (Courtesy Diagnostic Imaging Department, primary cause will be identified with other tests. However, it
Queen’s Veterinary School Hospital, University of is convenient from a classification point of view to split sec-
Cambridge, Cambridge, England.) ondary hepatopathies into three groups on the basis of their
appearance histopathologically—secondary hepatopathies
associated with hepatocyte swelling and/or vacuolation,
improve when the drug is withdrawn, although this has not hepatic congestion or edema, and reactive hepatitis.
yet been demonstrated. An alternative nonhepatotoxic
therapy for their epilepsy will need to be instituted; potas- HEPATOCYTE VACUOLATION
sium bromide might be an alternative choice, but it takes Secondary hepatopathies associated with hepatocyte vacu-
weeks to reach a steady state. Imepitoin is another alternative olation are divided into steroid-induced hepatopathy and
choice. Gabapentin might also be used, although this is only hepatocellular steatosis (lipidosis, fatty changes). Steroid-
effective in some dogs and does undergo some hepatic induced hepatopathy is characterized by hepatocellular gly-
metabolism. For more details, see Chapter 62. cogen accumulation, which is distinctive from steatosis, in
When an underlying cause cannot be identified and which fat (rather than glycogen) accumulates in hepatocytes.
treated, therapy is symptomatic and supportive. The most The difference can be demonstrated with special stains (peri-
important aspect is amino acid and protein supplementa- odic acid–Schiff for glycogen and Oil Red O or Sudan black
tion; in a few cases this may lead to long-term survival. There for fat), but there are also some differences on routine H&E
are single case reports of humans with resolution of the staining that help with differentiation. Glycogen vacuoles
disease after amino acid infusions and/or regular dietary tend not to displace the nucleus from the center of the cell
supplementation of egg protein; feeding egg yolks has also and often contain strands of eosinophilic material, whereas
been reported as resulting in a clinical improvement in some classic steatosis is associated with clear empty vacuoles
dogs. It is unclear whether eggs are beneficial simply because because the fat is lost in processing, and the nucleus is often
they are a high-quality amino acid supplement or whether displaced to the edge of the cell (Fig. 36.18).
there are other beneficial micronutrients in the eggs. Dogs Both types of vacuolar hepatopathies are reversible when
with hepatocutaneous syndrome should not be fed propri- the underlying cause is eliminated. The most common causes
etary diets for liver disease because these are protein- are endocrine diseases (see Table 36.1). Steroid-induced hep-
restricted. Other supportive therapy includes antibiotics for atopathy is seen in hyperadrenocorticism and dogs being
secondary skin infections (e.g., cephalexin, 20 mg/kg PO given exogenous corticosteroids. It has also been associated
q12h) and antioxidants (see earlier, “Chronic Hepatitis: with other hormone therapies and the administration of
Treatment”). In addition, zinc and fatty acid supplementa- some other drugs, such as D-penicillamine or barbiturates.
tion may be helpful in some cases. Glucocorticoids should There have been reports of idiopathic vacuolar hepatopa-
be avoided because they will precipitate diabetes mellitus. thy in Scottish Terriers causing marked elevations in ALP
Our group has treated two dogs with hepatocutaneous syn- levels, but the underlying cause is unknown. A large study
drome that survived for several years on a high-quality of Scottish Terriers with vacuolar hepatopathy at Cornell
digestible diet, marketed for GI disease, with extra egg and (Sepesy et al., 2006) suggested that these dogs had an over-
vitamin E and SAM-e supplementation with antibiotics; production of androgenic hormones, perhaps as a result
however, one dog did become diabetic 1 month after of a genetic defect in 21-hydroxylase. It is worrisome that
diagnosis. 30% of the Scottish Terriers in that study also developed