Recognizing and treating common liver diseases (Proceedings)
The so-called "reactive hepatopathies" which occur secondary to non-hepatic disease can result in increased serum biochemical hepatic tests and histomorphologic abnormalities. Most of the reactive hepatopathies cause increases in laboratory tests that evaluate hepatocellular integrity (ALT, AST) and tests of hepatic cholestasis (ALP, GGT). In most cases there are little if any changes in tests that evaluate hepatic function (bilirubin, albumin, glucose, and BUN). Most of the animals with secondary liver disease also retain normal serum bile acid concentrations, which again supports a concept that there is generally minimal hepatocellular dysfunction in most of these disease conditions.
This group is characterized by nonspecific hepatocellular degeneration or necrotic changes without evidence of significant chronic progressive inflammation. Again, these changes are usually secondary to manifestations of a primary non-hepatic disease. The reason the liver often undergoes these changes revolves from the fact that the liver is involved in many metabolic and detoxification functions. Endogenous toxins, anoxia, metabolic changes, nutritional changes and endogenous stress related glucocorticoid release are examples of conditions responsible for the majority of these changes. Non-specific mild liver changes routinely also occur following general anesthesia.A good example that helps explain this concept is inflammatory bowel disease in which it is not unusual to observe mild inflammatory changes around portal triads presumed to be the result of abnormal portal uptake of gastrointestinal "toxins". Throughout the liver and closely associated with portal areas are Kupffer cells (fixed macrophages) that function to filter the blood of injurious toxins, inflammatory mediators and bacteria. When this macrophage system is abnormally insulted Kupffer cells release their own inflammatory mediators that in turn insult the hepatocytes.
Another example could be the sick septic dog having vacuolar change thought to be due to endogenous cortisol release for endogenous stress and hepatic cholestasis from presumed endotoxin or cytokine alteration of bilirubin metabolism.
Histological findings associated with secondary reactive changes include descriptors such as vacuolar degeneration, hydropic degeneration, swollen hepatocytes, lipidosis, intracellular or intrahepatic cholestasis, mild multifocal hepatitis and periportal or variable hepatic necrosis. These changes are devoid of the typical progressive chronic inflammatory cell infiltrates characteristic of chronic hepatitis.
In a review of consecutive liver biopsies at Colorado State University histology grouped as non-specific reactive changes made up the largest category of abnormalities (approximately 25%) In this group we were able to identify an associated disease in many that could explain the likely cause for the hepatic enzyme increases and histological changes observed. Concurrent diseases identified included neoplasia, gastrointestinal, renal, autoimmune, dermatologic, dental, infectious and cardiac disease as a few examples. In some cases an underlying disease is not identified. The ALT values on the average are 1-2 X normal and the ALP values 1-3 X normal. It is interesting to note that in a series of 32 dogs having reactive hepatopathies, 8/8 cases in which serum bile acids were run, all were within the normal reference range again suggesting hepatic function remains intact.
This category appears to be the most common histological change to occur in dogs and is by far the most common cause of elevated liver enzymes. Based on this fact, dogs presented with elevations in ALT and ALP should always have primary non-hepatic disease ruled out first. These changes are usually very reversible and no specific hepatic therapy is required short of treating the primary disease. The liver changes resolve once the primary etiology is successfully treated. Therapy providing good liver support such as antioxidants may be warranted.