Liver disease in dogs



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Liver disease in dogs and humans {#Sec1}

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As with humans, liver disease in dogs is increasingly recognized in veterinary practice, and is associated with a variety of diseases, including chronic hepatitis, hepatic lipidosis, drug-induced liver injury and liver neoplasia.

Chronic hepatitis is an inflammatory process involving all stages of the hepatic parenchyma, and is characterized by fibrous scarring in pericentral areas, and variable inflammatory cell infiltration [[@CR1], [@CR2]]. In the USA, there are an estimated 1 million dogs with clinical signs of chronic hepatitis, and approximately 10% of these dogs will have an underlying hepatobiliary neoplasm [[@CR1]]. Canine hepatic lipidosis is an inherited disorder characterized by excess mobilization of stored fat, leading to hepatic lipid accumulation and fatty hepatopathy [[@CR1], [@CR2]]. As such, it may coexist with chronic hepatitis, and in rare cases hepatic lipidosis is the primary cause of hepatic disease in dogs [[@CR3]]. Liver neoplasia is the third most common cause of canine liver disease, and the most common tumour is hepatocellular carcinoma [[@CR1]]. Primary liver carcinoma, which represents 20% of canine primary liver tumours, is the most common primary liver neoplasm in dogs, with an annual incidence of 4--5 cases per million dogs [[@CR1], [@CR4]].

Diagnostic investigations {#Sec2}

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A full clinical examination should be performed in all dogs with suspected liver disease, and diagnostic imaging used in conjunction with a comprehensive haematological and biochemical analysis to confirm or exclude the possibility of liver disease. When considering liver disease in dogs, there are several investigations that should be considered and performed, including serum biochemical analysis, urinalysis, ultrasonography, computed tomography (CT) or magnetic resonance imaging (MRI), and liver biopsy. Each of these investigations has its own role to play in confirming or excluding liver disease.

Serum biochemistry {#Sec3}

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A full biochemical analysis is the first test to be performed in any patient with suspected liver disease. The test should include serum total bilirubin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, globulin, albumin/globulin ratio, total protein, and cholesterol [[@CR5]]. In chronic hepatitis, there is typically a shift towards an increased concentration of bilirubin and ALP, and a decrease in albumin and globulin concentration, leading to an increase in the albumin/globulin ratio [[@CR1], [@CR6]]. The presence of cholestasis in dogs is indicated by increased concentrations of total bilirubin, ALP and γ-glutamyl transpeptidase (GGT), and decreased concentrations of albumin and cholesterol [[@CR6]]. In hepatic lipidosis, there is typically a reduction in serum cholesterol concentration, although concentrations can also be normal or mildly elevated [[@CR2]]. The concentration of serum alkaline phosphatase is increased in the majority of dogs with neoplastic liver disease, but a low concentration of this enzyme is suggestive of an underlying liver neoplasm [[@CR4], [@CR5]]. Similarly, the concentration of serum total bilirubin may be mildly to severely elevated in dogs with primary liver tumours, and therefore the ratio of albumin to total bilirubin (ALB:TBIL) may be useful to help differentiate hepatocellular carcinoma from primary cholangiocellular carcinoma [[@CR5], [@CR7]]. The concentration of ALT is mildly to moderately increased in the majority of dogs with hepatic lipidosis, as well as chronic hepatitis, while the concentration of AST is more consistently increased, and is often used as a confirmatory diagnostic tool for the presence of liver disease [[@CR1], [@CR6]]. The concentration of total protein is often increased in dogs with liver disease, but is not specific to the disease [[@CR1], [@CR6]]. Dogs with liver lipidosis often have a mildly increased concentration of cholesterol, however this should not be a primary diagnostic tool as many dogs with liver lipidosis have normal serum cholesterol concentrations [[@CR2]].

Urinalysis {#Sec4}

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As an initial test, urinalysis should be performed in any dog with suspected liver disease. The test should include specific gravity, urine protein to creatinine ratio, and urine β~2~-microglobulin:creatinine ratio [[@CR8]]. Urine specific gravity should be measured, as dogs with normal liver function will have urine specific gravity similar to urine of healthy dogs. The concentration of protein in the urine is usually increased in dogs with liver disease, and the urine protein:creatinine ratio can therefore be useful in confirming the diagnosis [[@CR1], [@CR2], [@CR6], [@CR8]]. Urine β~2~-microglobulin:creatinine ratio may be increased in dogs with chronic hepatitis, and can be used to help differentiate between chronic hepatitis and hepatic lipidosis [[@CR8]]. As a urine test, β~2~-microglobulin is an indicator of tubular dysfunction and renal function, and has been shown to be an effective marker of renal function in patients with liver disease [[@CR9]].

Ultrasonography {#Sec5}

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Ultrasonography is a non-invasive, inexpensive and relatively easy test to use in veterinary practice [[@CR10]]. It is primarily used for abdominal imaging, with a lateral, dorsal



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