August 26, 2017

Biomarker Sensitivity for Early Detection of Canine Liver Disease

Researchers sought to determine the sensitivity of biochemical indicators for detecting acute and chronic hepatitis in Labrador retrievers.
By Laurie Anne Walden, DVM, ELS
In a study recently published in the Journal of Veterinary Internal Medicine, researchers found that plasma alanine aminotransferase (ALT) activity, alkaline phosphatase (ALP) activity, and bile acid concentration all had low sensitivity for detecting hepatitis in a population of Labrador retrievers. The investigators said that early detection of liver disease in clinically healthy dogs requires more sensitive biomarkers.

Biomarkers of liver disease can reflect either primary or reactive hepatitis, they wrote. Two forms of primary hepatitis are chronic hepatitis (often idiopathic) and acute hepatitis (idiopathic or caused by toxins, infections, or other agents). Reactive hepatitis is a liver response to extrahepatic disorders such as pancreatitis.

Chronic hepatitis has a long subclinical stage during which dogs appear healthy. The disease may not be diagnosed until it is advanced, at which point the prognosis is guarded, said the authors. “For successful management of the disease, early identification of (subclinical) dogs with [primary hepatitis] is of great importance,” they wrote.

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The researchers retrospectively reviewed the records of 51 Labrador retrievers referred to the Department of Clinical Sciences of Companion Animals, Utrecht University, the Netherlands, because of elevated liver enzyme levels or clinical signs suggestive of hepatitis. They also examined the records of 191 clinically healthy Labrador retrievers participating in a study of copper-associated hepatitis. The healthy dogs were either first-degree relatives of dogs with copper-associated hepatitis or were being screened before breeding.

Blood and ultrasound-guided liver biopsy samples were collected from all dogs. Biopsy samples were submitted for histopathologic analysis and copper assessment.

Livers were classified by histopathology as normal, primary hepatitis, or reactive hepatitis. Primary hepatitis was subdivided into acute and chronic disease.

Of the 242 livers submitted for histopathology, 38% were classified as reactive hepatitis; 28% normal; 23% chronic hepatitis; and 11% acute hepatitis. ALT, ALP, and bile acids were higher in dogs with acute or chronic hepatitis than in those with reactive hepatitis or normal livers.

Of the 191 clinically healthy dogs, 122 were considered subclinically affected with liver disease because of abnormal findings on histopathology (most of these dogs had reactive hepatitis). Of the 51 dogs with clinical illness, 88% had primary hepatitis.
 
Overall, histologic signs of liver disease were identified in 173 dogs (122 subclinically affected and 51 clinically ill). Over half of these dogs had ALT, ALP, and bile acids within the reference range.

Copper concentrations were highest in livers with histopathologic signs of acute hepatitis and lowest in normal livers. Hepatic copper concentration was not associated with differences in ALT, ALP, or bile acids.

The sensitivity of ALT was 71% for detecting chronic hepatitis but only 45% for detecting acute hepatitis. The sensitivities of ALP and bile acids were 35% or lower for detecting either chronic or acute hepatitis. In addition, ALP and bile acids could not distinguish between primary and reactive hepatitis. The odds of having primary hepatitis rose with increasing ALT.

The low sensitivities found in this study could reflect the generally mild liver changes seen on histopathology, said the authors. They also noted that reference ranges are based on clinically normal animals and are not usually corroborated by histopathology; therefore, the reference ranges could be too high for this population.

Many of the healthy dogs in this study were closely related to dogs with copper-associated hepatitis. Copper toxicosis can cause acute or chronic liver disease, and copper-associated hepatitis is hereditary in Labrador retrievers. Some of the healthy dogs included in the study could have been predisposed to hepatitis, say the authors, noting that their results might not be translatable to other dog populations.

The authors concluded that although the sensitivity of ALT for detecting chronic hepatitis was “reasonable,” it was poor for detecting acute and reactive hepatitis. ALP and bile acids could not detect acute, chronic, or reactive hepatitis in this population.

 
Dr. Walden received her doctorate in veterinary medicine from North Carolina State University. After an internship in small animal medicine and surgery at Auburn University, she returned to North Carolina, where she has been in small animal primary care practice for over 20 years. Dr. Walden is also a board-certified editor in the life sciences and owner of Walden Medical Writing, LLC. She works as a full-time freelance medical writer and editor and continues to see patients a few days each month.

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