High ALT in Dogs: Causes, Interpretation & Next Steps
In dogs, ALT is an aminotransferase with high diagnostic utility to detect liver injury or lesions because hepatic ALT activity is 10,000-fold greater than plasma enzyme activity in healthy animals, but increased ALT is not fully specific for clinically significant liver disease [5][1].
In dogs with clinical signs, any increase in serum transaminases should be investigated, while smaller increases in subclinical dogs can be rechecked to determine whether they persist [1].
A published dog approach classifies mild ALT increases as up to 2-fold, moderate increases as 2- to 5-fold, and severe increases as 5-fold increases, with progressively more urgent diagnostic workup as severity or persistence increases [3][4].
Key points
- ALT meaning: In dogs, ALT has high diagnostic utility to detect liver injury or lesions because hepatic ALT activity is 10,000-fold greater than plasma enzyme activity in healthy animals [5].
- Not fully specific: In dogs, serum ALT can be elevated without clinically significant liver disease, particularly with disorders that affect the GI tract, pancreatic disorders, or endocrine disorders such as hyperadrenocorticism [1].
- Clinical dogs: In dogs with clinical signs, any increase in serum transaminases should be investigated [1].
- Subclinical dogs: In subclinical dogs, there is some evidence that increases 4 times more than normal that last >12 weeks should trigger investigation, and smaller increases should be rechecked in 4 to 6 weeks [1].
- Magnitude guides urgency: In dogs, mild ALT increases up to 2-fold can be rechecked every 2 weeks, moderate increases 2- to 5-fold require a diagnostic workup, and severe increases 5-fold or persistent increases in ALT warrant an immediate diagnostic workup, likely including liver biopsies [3][4].
What it measures
In dogs, ALT is an aminotransferase commonly used to infer liver injury in questions of hepatic disease, and ALT activity is highest in liver [5].
In dogs, the cytosolic location of transaminases allows immediate release with even minor alteration in hepatocyte cell membrane integrity [5].
Causes
In dogs, increased ALT can reflect primary hepatocellular disease, congenital vascular disease, breed-associated hepatopathy, or nonhepatic disorders [1][7].
| Category | Causes |
|---|---|
| Primary hepatocellular disease | chronic hepatitis, copper-associated hepatitis, hepatotoxicity, infection [7] |
| Breed-associated hepatopathy | immune-mediated or copper-associated hepatitis in Doberman pinschers, American and English cocker spaniels, Labrador retrievers, Bedlington terriers, Dalmatians, West Highland white terriers, and English springer spaniels [1] |
| Congenital vascular disease | portosystemic vascular anomalies; primary hypoplasia of the portal vein [1] |
| Nonhepatic or secondary disorders | disorders that affect the GI tract; pancreatic disorders; hyperadrenocorticism in dogs [1] |
How to interpret it
In dogs, the magnitude and persistence of ALT change help determine how aggressively to investigate the result [1][3][4][5].
- Serial trend: In dogs, duration and magnitude of serum transaminase activity measured sequentially can predict disease activity and severity and roughly estimate the magnitude of hepatocyte involvement [5].
- Normal ALT: In one dog, ALT and AST activities within normal limits made hepatocellular damage unlikely [2].
- Hepatocellular pattern: In one dog, ALT activity 2.4 times the upper limit of the reference interval with increased serum AST activity and ALP activity only 1.3 times the upper limit of the reference interval was consistent with a hepatocellular damage pattern [2].
- AST pairing: In dogs, AST often parallels changes in ALT activity [5].
- Persistence matters: In subclinical dogs, smaller increases in serum transaminases should be rechecked in 4 to 6 weeks to determine whether elevations persist [1].
Next diagnostic steps
In dogs, interpret increased ALT in the context of the whole patient before choosing serial monitoring or a full diagnostic workup [1].
- Examine the entire clinical scenario in the dog, including patient history, clinical signs, physical examination findings, diagnostic imaging, and ancillary laboratory evaluation, to determine the clinical significance of persistently elevated ALT [1].
- In dogs with clinical signs, investigate any increase in serum transaminases [1].
- In subclinical dogs, recheck smaller increases in serum transaminases in 4 to 6 weeks to determine whether elevations persist [1].
- In subclinical dogs, there is some evidence that increases 4 times more than normal that last >12 weeks should trigger investigation [1].
- Another published dog approach recommends rechecking mild ALT increases up to 2-fold every 2 weeks, with further investigation if the increase persists more than 4–6 weeks [3][4].
- In dogs, moderate ALT increases 2- to 5-fold require a diagnostic workup, such as liver function assays (bile acids or ammonia) and leptospirosis serology/PCR [3][4].
- In dogs, severe ALT increases 5-fold or persistent increases in ALT warrant an immediate diagnostic workup, likely including liver biopsies [3][4].
Related results to check
In dogs, moderate increases in ALT (2- to 5-fold increases) require a diagnostic workup (e.g., liver function assays [bile acids or ammonia] and leptospirosis serology/PCR). [3]
- AST: In dogs, serum AST activity often parallels changes in ALT activity [5].
- ALP: In one dog, ALT activity 2.4 times the upper limit of the reference interval with ALP activity only 1.3 times the upper limit of the reference interval supported a hepatocellular damage pattern rather than a cholestatic pattern [2].
- Bile acids or ammonia: In dogs, liver function assays such as bile acids or ammonia are part of the diagnostic workup for moderate ALT increases [3][4].
- Ammonia and SBA: In one dog, the ammonia concentration and serum bile acid results suggested portosystemic shunting and/or hepatic insufficiency [2].
- Albumin, BUN, and cholesterol: In one dog, hypoalbuminemia, decreased BUN, and hypocholesterolemia suggested decreased hepatic synthetic capacity [2].
Frequently asked questions
When should a dog with increased ALT be investigated?
What ALT increase is considered mild, moderate, or severe in dogs?
What additional tests are recommended for a dog with increased ALT?
In dogs, a published approach recommends liver function assays such as bile acids or ammonia and leptospirosis serology/PCR for moderate ALT increases [3][4]. In dogs, the significance of persistently elevated ALT should also be assessed with patient history, clinical signs, physical examination findings, diagnostic imaging, and ancillary laboratory evaluation [1].
Can a dog have increased ALT without clinically significant liver disease?
In dogs, serum ALT can be elevated without clinically significant liver disease, particularly in disorders that affect the GI tract and pancreas and in endocrine disorders such as hyperadrenocorticism [1].
Does increased ALT with increased AST and only mild ALP increase suggest hepatocellular damage in dogs?
In one dog, ALT activity 2.4 times the upper limit of the reference interval with increased serum AST activity and ALP activity only 1.3 times the upper limit of the reference interval was consistent with a hepatocellular damage pattern [2].
References
- Interpretation of Serum Transaminase Levels in Dogs & Cats
Passage read from this source
Serum chemistry profiles in dogs and cats frequently detect increases in serum ALT or AST activity. In a study that included 1,022 blood samples from both healthy and sick dogs, serum ALT and AST activity increased in 17% and 11% of dogs, respectively.5 In a separate study that included 407 healthy middle-aged dogs and 128 cats, serum ALT and AST activity were increased in 9.3% and 2% of dogs, respectively.6 Serum ALT and AST activity were both increased in 7% of cats.
Breed Predisposition - Increases in serum ALT or AST activity may be the first indicator of congenital or acquired breed-specific diseases in dogs and cats.1-4,7,8 - Examples include - Immune-mediated or copper-associated hepatitis9,10 - Doberman pinschers - American and English cocker spaniels - Labrador retrievers - Bedlington terriers - Dalmatians - West Highland white terriers - English springer spaniels - Serum transaminase levels are often mildly elevated in dogs (less often in cats) with congenital vascular diseases (eg, portosystemic vascular anomalies, primary hypoplasia of the portal vein) and in dogs with disorders with distinct canine breed predispositions.8,9
The entire clinical scenario, including patient history, clinical signs, physical examination findings, diagnostic imaging, and ancillary laboratory evaluation, should be examined to determine the clinical significance of persistently elevated levels of serum ALT or AST. The magnitude of increase in serum ALT and AST activity necessary to trigger a thorough clinical investigation has not been determined. In dogs with clinical signs, any increase in serum transaminases should be investigated. In subclinical dogs, there is some evidence that increases 4 times more than normal that last >12 weeks should trigger investigation.16 Smaller increases in subclinical patients should be rechecked in 4 to 6 weeks to determine whether elevations persist. Similar studies have not been done in cats.
- Serum ALT or AST can be elevated without the presence of clinically significant liver disease, particularly in disorders that affect the GI tract and the pancreas in endocrine disorders (eg, hyperthyroidism in cats, hyperadrenocorticism in dogs).
- Liver Enzyme Interpretation and Liver Function Tests
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***Signalment and Presentation*** A 3-month-old female intact Irish wolfhound presents for stunted growth and episodes of intermittent lethargy and disorientation. ***Results of Diagnostic Testing*** A serum biochemistry panel is performed, with the results in **Table A**. The fasted ammonia concentration is 175 mcg/dL (normal range, 0–50 mcg/dL). Preprandial and postprandial (2-hour) SBA are 40 mcmol/L (normal, 0–8 mcmol/L) and 102 mcmol/L (normal, 0–30 mcmol/L), respectively. ***Interpretation*** The combination of hypoalbuminemia, decreased BUN, and hypocholesterolemia suggests decreased hepatic synthetic capacity. The ALT and AST activities are within normal limits, making hepatocellular damage unlikely; the ALP activity is only mildly elevated, probably because the dog is growing. The ammonia concentration and SBA results suggest portosystemic shunting and/or hepatic insufficiency.
***Signalment and Presentation*** An 8-year-old male neutered Labrador retriever presents for a 3-month history of decreased appetite and weight loss. ***Results of Diagnostic Testing*** A serum biochemistry panel is performed, with the results in **Table B**. The fasted ammonia concentration is
ALP is an enzyme found in hepatocytes that line the bile canaliculi. It is released into the circulation during intra- or extrahepatic cholestasis. This enzyme is sensitive for hepatobiliary disease in dogs (80%), but because of the possible contributions of bone and glucocorticoid-induced isoenzymes to serum ALP activity, its specificity is low (51%).5 In young, growing animals, ALP activity is normally increased because of the bone isoenzyme, with 71% of dogs younger than 1 year having ALP activity >150 U/L.6 Bone ALP may also be elevated in patients with osteomyelitis or osteosarcoma. Dogs with hyperadrenocorticism and those receiving glucocorticoids can be expected to have increased ALP activity due to the glucocorticoid-induced isoenzyme. Conditions that can cause an increase in ALP…
The enterohepatic recirculation of bile acids is impeded in dogs without gallbladders and patients with ileal disease or that have had ileal resection, causing a decrease in SBA concentration. Other conditions that can cause decreased SBA concentrations include GI malabsorption and decreased gastric motility.2 Causes of increased total SBA concentrations are listed in Box 2. Diseases that cause intrahepatic cholestasis (lipidosis, diabetes mellitus, lymphoma, histoplasmosis, cirrhosis) or extrahepatic cholestasis (cholangitis, bile duct carcinoma, liver flukes, cholelithiasis, pancreatitis) can cause decreased bile acid excretion, despite no decrease in functional hepatic mass. In patients with hyperbilirubinemia, once hemolysis has been ruled out, measuring SBA is not indicated because their concentration will be predictably increased.
- How I Approach a Dog with Increased Serum ALT
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Generally speaking * Mild increases (up to 2-fold) can be rechecked every 2 weeks and possibly treated with nutraceutical hepatoprotectants. If increase persists more than 4–6 weeks, further investigation is warranted. * Moderate increases (2- to 5-fold increases) require a diagnostic workup (e.g., liver function assays [bile acids or ammonia] and leptospirosis serology/PCR). * Severe increases (5-fold increases) or persistent increases in ALT warrant an immediate diagnostic workup, likely including liver biopsies. Table 1. Causes of increased serum ALT activities in dogs Primary Hepatopathies
- How I Approach a Dog with Increased Serum ALT
Passage read from this source
Generally speaking * Mild increases (up to 2-fold) can be rechecked every 2 weeks and possibly treated with nutraceutical hepatoprotectants. If increase persists more than 4–6 weeks, further investigation is warranted. * Moderate increases (2- to 5-fold increases) require a diagnostic workup (e.g., liver function assays [bile acids or ammonia] and leptospirosis serology/PCR). * Severe increases (5-fold increases) or persistent increases in ALT warrant an immediate diagnostic workup, likely including liver biopsies. Table 1. Causes of increased serum ALT activities in dogs Primary Hepatopathies
- Enzyme Activity in Hepatic Disease in Small Animals
Passage read from this source
AST and ALT are aminotransferases commonly used to infer liver injury in questions of hepatic disease. However, both enzymes are present in high concentrations in liver and several other tissues. AST activity is higher in kidney, heart, and skeletal muscle than liver, whereas ALT activity is highest in liver. Because hepatic ALT activity is 10,000-fold greater than plasma enzyme activity in healthy animals, it has high diagnostic utility to detect liver injury or lesions. The cytosolic location of transaminases allows their immediate release with even minor alteration in hepatocyte cell membrane integrity. Unfortunately, indiscriminate leakage limits the specificity of their diagnostic utility. Nonetheless, duration and magnitude of serum transaminase activity measured sequentially can predict disease activity and severity and roughly…
AST is present in substantial concentrations in a wide variety of tissues, especially muscle. Increased AST activity can reflect reversible or irreversible changes in hepatocyte cell membrane permeability, hepatocyte mitochondrial membrane damage, cell necrosis, hepatic inflammation, and, in dogs, microsomal enzyme induction. After acute diffuse severe hepatic necrosis, serum AST sharply increases during the first 3 days to values 10- to 30-fold above normal in dogs and up to 50-fold above normal in cats. If necrosis resolves, AST activity gradually declines over 2–3 weeks. In most cases, AST parallels changes in ALT activity.
Increased alkaline phosphatase (ALP) activity in dogs is the most common abnormality on routine biochemical testing for hepatic disease; its high sensitivity and low specificity can defy diagnostic interpretation without liver biopsy. ALP activity in dogs has the lowest specificity of routinely used liver enzymes because of the complexity associated with induction of different isozymes.
Although serum activity of ALP may be normal or only modestly increased in dogs with metastatic neoplasia involving the liver, it may also increase dramatically in dogs with mammary neoplasia. High serum ALP activity develops in ~50% of dogs with malignant or benign mammary tumors, with highest ALP activity reported in dogs with malignant mixed tumors. Nevertheless, serum ALP has no value as a diagnostic or prognostic marker in mammary cancer; it remains unclear whether disease remission (surgical, chemotherapy) is followed by a regression in serum ALP activity or whether serum ALP activity functions as a paraneoplastic marker.
- Diagnostic approach in dogs with increased ALP activity ...
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Author(s)Susan E. Johnson, DVM, MS, DACVIM An increase in serum alkaline phosphatase (ALP) activity is a common laboratory finding in dogs. It is typically used as a diagnostic marker for cholestatic liver disease. However, increased ALP activity has a high sensitivity (86%) but poor specificity (49%) for canine liver disease. Advertisement Shutterstock.com Hi! We made an updated version of this article in 2018. Click here to check it out.
Evaluation for the cause of increased serum ALP activity should include a complete history, physical examination, and laboratory tests consisting of a CBC, biochemical profile, and urinalysis. Review of this initial database of information will usually provide insights into many of the causes of increased ALP activity, and will often suggest the next diagnostic step. For example, dogs less than 15 months of age with mild increases in ALP activity (< 2 times upper limit of normal), are often due to increased B-ALP, from normal bone growth. Concurrent mild increases in calcium and phosphorus are often present. These findings are consistent with a normal age-related variation, and do not require further investigation. A complete drug history, (especially glucocorticoids and phenobarbital)…
- Diagnostic approach to increased liver enzyme activities in ...
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Primary hepatocellular diseases characterized by increased serum ALT activity include chronic hepatitis, copper-associated hepatitis, hepatotoxicity, infection ...
- High Liver Enzymes - WSAVA 2018 Congress - VIN
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ALT has a half-life of 6 hours in a cat and 48–60 hours in a dog, making it a good indicator of continued liver injury.1 … its increase indicates cell death. ...
- A descriptive study of the histopathologic and biochemical ...
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by SN Assawarachan · 2020 · Cited by 27 — Elevation of ALT, ALP, or a combination of ALT and ALP had a high sensitivity of up to 90% for identifying dogs with liver pathology.
- Why Are Liver Enzymes Increased? - WSAVA 2014 Congress
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Persistent elevations or increase over weeks is characteristic of chronic hepatitis in the dog or other chronic long standing damage. As a general rule, ALT ...
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