History
A 6-month-old 20.2-kg (44.4-lb) sexually intact female Labrador Retriever was evaluated at a veterinary teaching hospital because of a 10-day history of anorexia, vomiting, and lethargy and a 4-day history of ascites. Eleven days prior to the evaluation at the hospital, the dog had been examined by the referring veterinarian because of acute vomiting. Abdominal radiography revealed no abnormalities. The dog was sent home, and the owner was instructed to provide supportive care for suspected gastroenteritis. The dog was reexamined 5 days later because of a lack of improvement. At that time (day 6), results of a CBC were unremarkable except for mildly low RBC count (5.37 × 106 RBCs/μL; reference interval, 5.50 × 106 RBCs/μL to 8.50 × 106 RBCs/μL) and mild neutrophilia (12.16 × 103 neutrophils/μL; reference interval, 3.0 × 103 neutrophils/μL to 11.4 × 103 neutrophils/μL). Serum biochemical analysis revealed high alkaline phosphatase (ALP) and alanine aminotransferase (ALT) activities, hyperbilirubinemia, hypocholesterolemia, hypoalbuminemia, hypoproteinemia, and hyponatremia (Table 1). Three days later, the dog developed ascites and was transferred to a specialty clinic.
Serum biochemical abnormalities detected initially (day 6) and subsequently (day 10) in a 6-month-old Labrador Retriever that was evaluated because of a 10-day history of anorexia, vomiting, and lethargy and a 4-day history of ascites.
| Variable | Reference interval | Day 6 | Day 10 |
|---|---|---|---|
| Sodium (mEq/L) | 141–151 | 129 | 141 |
| Potassium (mEq/L) | 3.9–5.3 | 5.5 | 3.2 |
| Chloride (mEq/L) | 112–121 | NA* | 108 |
| Calcium (mg/dL) | 9.7–11.3 | 9.6 | 8.3 |
| Phosphorus (mg/dL) | 3.2–6.0 | 5.8 | 5.4 |
| Magnesium (mg/dL) | 1.70–2.50 | NA | NA |
| SUN (mg/dL) | 10–30 | 10 | 7 |
| Creatinine (mg/dL) | 0.5–1.5 | 0.6 | 0.5 |
| Glucose (mg/dL) | 68–115 | 108 | 104 |
| Total protein (g/dL) | 5.2–7.1 | 4.3 | 3.9 |
| Albumin (g/dL) | 2.7–4.0 | 2.4 | 1.7 |
| Alkaline phosphatase (U/L) | 20–150 | 604 | 440 |
| Alanine aminotransferase (U/L) | 24–90 | 143 | 176 |
| Total bilirubin (mg/dL) | < 0.1–0.60 | 3.5 | 1.3 |
| Cholesterol (mg/dL) | 132–300 | 43 | 30 |
Value for day 6 was not reported, but a repeated electrolyte panel 2 days later revealed serum chloride concentration of 111 mEq/L.
NA = Not available.
Previous Clinical and Clinicopathologic Findings
At the specialty clinic, abdominal ultrasonography revealed that the dog had a subjectively small liver with decreased portovascular markings and a moderate amount of peritoneal effusion. A tentative diagnosis of a portosystemic shunt was made, and the dog was administered fluid therapy, maropitant citrate, ampicillin, lactulose, and S-adenosylmethionine–silybin A and B. On day 10, serum biochemical analysis revealed a continued increase in ALT activity, high although improved ALP activity and total bilirubin concentration, and persistent hypocholesterolemia and hypoalbuminemia (Table 1). A coagulation panel revealed prolonged prothrombin time (22 seconds; reference interval, 11 to 17 seconds) and partial thromboplastin time (140 seconds; reference interval, 72 to 102 seconds). Given the hypocholesterolemia, hypoalbuminemia, low SUN concentration, and prolonged clotting times, there was a concern for hepatic insufficiency, and the dog underwent assessment of pre- and postprandial bile acids concentrations. The pre- and postprandial bile acids concentrations were 24.7 μmol/L (reference interval, 0 to 5.9 μmol/L) and 74.4 μmol/L (reference interval, 0 to 14.9 μmol/L), respectively, which likely reflected a decrease in functional hepatic mass; however, cholestasis can also increase bile acids concentrations and may have been a contributing factor. Abdominocentesis was performed, and approximately 1,200 mL of pure transudate (clear; total solids concentration, 0.4 g/dL; no nucleated cells) was removed. The dog was then transferred to the veterinary teaching hospital for advanced diagnostic imaging and continued medical management.
Formulate differential diagnoses from the history, clinical findings, and Table 1—then turn the page→
Clinical and Clinicopathologic Findings
On physical examination at the veterinary teaching hospital (day 12), the dog's abdomen was severely distended with a visible fluid wave on palpation. There were multifocal petechiae present on the ventral aspect of the dog's abdomen and the mucous membranes were visibly icteric. Abdominocentesis yielded 1,375 mL of pure transudate (protein concentration, 0.6 g/dL; total nucleated cell count, 340 cells/μL). Hematologic abnormalities were similar to previous findings, along with low platelet count (155 × 103 platelets/μL; reference interval, 200 × 103 platelets/μL to 500 × 103 platelets/μL). Serum biochemical analyses were repeated (Table 2). Resting circulating cortisol concentration was within the reference interval (2.94 μg/dL; reference interval, 1 to 5 μg/dL). The dog was seronegative for anti-Leptospira antibodies. Abdominal ultrasonography revealed a large volume of free peritoneal fluid and a hyperechoic line within the wall of the gallbladder, which likely represented a mineral substance. Fine-needle aspirate specimens of the liver and bile were collected for cytologic examination and microbial culture. The liver aspirate specimen had a moderate number of leukocytes with a high number of neutrophils, compared with findings for a sample of peripheral blood. On examination, the bile aspirate specimen appeared normal. Microbial cultures of the liver and bile aspirate specimens yielded no growth. The dog was anesthetized, and abdominal CT was performed to evaluate for a portosystemic shunt. The CT findings included persistence of the peritoneal effusion, subcutaneous ventral edema, pancreatic edema, mildly enlarged mesenteric lymph nodes, and faint gallbladder wall mineralization.
The dog was hospitalized and treated supportively with fluid therapy, gastroprotectants, antioxidants (N-acetylcysteine and α-tocopherol), ursodiol, enteral nutrition, ampicillin sulbactam, and metronidazole. The dog became hypotensive, requiring norepinephrine to maintain blood pressure, and its ascites progressed. Clinicopathologic analyses were repeated (day 14) and revealed an inflammatory leukogram, decreases in albumin concentration and ALT and ALP activities, and increases in total bilirubin and cholesterol concentration, compared with findings on day 12 (Table 2). An additional sample of abdominal fluid was collected to assess for peritonitis secondary to collection of fine-needle aspirate specimens. The fluid was consistent with a pure transudate (protein concentration, < 0.1 g/dL; total nucleated cell count, 500 cells/μL) that contained a low number of nondegenerate neutrophils, which may have been attributable to blood contamination (low to moderate numbers of erythrocytes were also noted), chronicity of the effusion, or early inflammation. At this time, euthanasia was elected and the dog was submitted for necropsy.
Histopathologic Findings
On gross postmortem examination, ventral subcutaneous edema, ascites, and a diffusely pale, shrunken, and micronodular liver were identified (Figure 1). Microscopic examination of sections of liver tissue revealed diffuse dissection of hepatic lobules by fine bands of fibrous connective tissue (confirmed with trichrome staining), often accompanied by low numbers of lymphocytes and plasma cells, and multifocal regenerative nodules. Additional histologic findings included variable vacuolation of hepatocytes, which was predominantly lipid type, biliary hyperplasia, and occasional binucleated hepatocytes. These findings were consistent with lobular dissecting hepatitis. Copper was not detected in liver tissue with rhodanine stain.
Photograph of the liver (A) and photomicrograph of a section of liver tissue (B) from a 6-month-old Labrador Retriever that was evaluated because of a 10-day history of anorexia, vomiting, and lethargy and a 4-day history of ascites. A—The liver is slightly smaller than expected in a dog of this age and breed, is pale, and has a smooth to micronodular surface. B—Hepatic lobules are dissected by bands of fibrous connective tissue, resulting in individualized (arrows) and small clusters of hepatocytes. There are occasionally low numbers of lymphocytes and plasma cells (arrowhead) and an abnormal proportion of bile ductule profiles (ie, biliary hyperplasia [asterisks]). H&E stain; bar = 10 μm. Inset—In another section of liver tissue, collagen fibers are highlighted (blue-stained material) following trichrome staining. Trichrome stain; bar = 10 μm.
Citation: Journal of the American Veterinary Medical Association 256, 3; 10.2460/javma.256.3.315
Photograph of the liver (A) and photomicrograph of a section of liver tissue (B) from a 6-month-old Labrador Retriever that was evaluated because of a 10-day history of anorexia, vomiting, and lethargy and a 4-day history of ascites. A—The liver is slightly smaller than expected in a dog of this age and breed, is pale, and has a smooth to micronodular surface. B—Hepatic lobules are dissected by bands of fibrous connective tissue, resulting in individualized (arrows) and small clusters of hepatocytes. There are occasionally low numbers of lymphocytes and plasma cells (arrowhead) and an abnormal proportion of bile ductule profiles (ie, biliary hyperplasia [asterisks]). H&E stain; bar = 10 μm. Inset—In another section of liver tissue, collagen fibers are highlighted (blue-stained material) following trichrome staining. Trichrome stain; bar = 10 μm.
Citation: Journal of the American Veterinary Medical Association 256, 3; 10.2460/javma.256.3.315
Photograph of the liver (A) and photomicrograph of a section of liver tissue (B) from a 6-month-old Labrador Retriever that was evaluated because of a 10-day history of anorexia, vomiting, and lethargy and a 4-day history of ascites. A—The liver is slightly smaller than expected in a dog of this age and breed, is pale, and has a smooth to micronodular surface. B—Hepatic lobules are dissected by bands of fibrous connective tissue, resulting in individualized (arrows) and small clusters of hepatocytes. There are occasionally low numbers of lymphocytes and plasma cells (arrowhead) and an abnormal proportion of bile ductule profiles (ie, biliary hyperplasia [asterisks]). H&E stain; bar = 10 μm. Inset—In another section of liver tissue, collagen fibers are highlighted (blue-stained material) following trichrome staining. Trichrome stain; bar = 10 μm.
Citation: Journal of the American Veterinary Medical Association 256, 3; 10.2460/javma.256.3.315
Morphologic Diagnosis and Case Summary
Morphologic diagnosis and case summary: lobular dissecting hepatitis (LDH) in a juvenile Labrador Retriever.
Serum biochemical abnormalities detected initially (day 6) and subsequently (days 10, 12, and 14) in the dog in Table 1.
| Variable | Reference interval | Day 6 | Day 10 | Day 12 | Day 14 |
|---|---|---|---|---|---|
| Sodium (mEq/L) | 141–151 | 129 | 141 | 137 | 150 |
| Potassium (mEq/L) | 3.9–5.3 | 5.5 | 3.2 | 5.4 | 3.7 |
| Chloride (mEq/L) | 112–121 | NA* | 108 | 107 | 118 |
| Calcium (mg/dL) | 9.7–11.3 | 9.6 | 8.3 | 9.1 | 9.3 |
| Phosphorus (mg/dL) | 3.2–6.0 | 5.8 | 5.4 | 7.1 | 6.6 |
| Magnesium (mg/dL) | 1.70–2.50 | NA | NA | 2.26 | 2.48 |
| SUN (mg/dL) | 10–30 | 10 | 7 | 14 | 26 |
| Creatinine (mg/dL) | 0.5–1.5 | 0.6 | 0.5 | 0.8 | 0.9 |
| Glucose (mg/dL) | 68–115 | 108 | 104 | 99 | 106 |
| Total protein (g/dL) | 5.2–7.1 | 4.3 | 3.9 | 3.6 | 3.1 |
| Albumin (g/dL) | 2.7–4.0 | 2.4 | 1.7 | 1.6 | 1.3 |
| Alkaline phosphatase (U/L) | 20–150 | 604 | 440 | 378 | 275 |
| Alanine aminotransferase (U/L) | 24–90 | 143 | 176 | 214 | 201 |
| Total bilirubin (mg/dL) | < 0.1–0.60 | 3.5 | 1.3 | 1.63 | 1.94 |
| Cholesterol (mg/dL) | 132–300 | 43 | 30 | < 50 | 52 |
See Table 1 for key.
Comments
Hepatitis of 4 to 6 months’ duration is considered chronic. Chronic hepatitis is characterized by hepatocellular necrosis with a mixed inflammatory cell infiltrate and results in cirrhosis and fibrosis.1 The cause of chronic hepatitis is generally unknown, and the term is used to describe a variety of conditions that cause inflammatory disease within the liver.2 Categories of chronic hepatitis in dogs include copper associated, infectious, drug or toxin induced, and idiopathic.
Lobular dissecting hepatitis is an idiopathic form of chronic hepatitis that most often develops in juvenile dogs, and it has been likened to human neonatal hepatitis.3 Among dogs, the age at which clinical signs become apparent can vary and has been reported to be 3 months to 7.2 years.3,4 Lobular dissecting hepatitis has been detected in various breeds including the Standard Poodle, Golden Retriever, Rottweiler, Mastino Espagnol, American Cocker Spaniel, English Cocker Spaniel, Large Münsterländer, Border Collie, West Highland White Terrier, Tibetan Mastiff, German Pointer, German Shepherd Dog, Belgian Sheepdog, Bernese Mountain Dog, Fox Terrier, Jack Russell Terrier, and Stabyhoun; mixed-breed dogs have also been affected.3–5 In 1 report5 of dogs with LDH, sexually intact females were overrepresented. Clinical signs are consistent with those seen with chronic hepatitis and include abdominal distension, weight loss, gastrointestinal tract signs, polyuria, and polydipsia. Affected dogs typically have signs of ascites or jaundice (or both) on physical examination.
Serum biochemical changes are characterized by normal to high ALT and ALP activities, high bile acids concentration, and hypoalbuminemia.3–5 In 1 study,4 mean serum protein concentration in dogs with LDH was significantly lower than that in dogs with other types of hepatitis. In dogs with LDH, the protein and cell contents of the peritoneal effusion are low and the effusion is categorized as a pure transudate.5 Prolonged bleeding times have been documented for many dogs with LDH.3 In a report by Poldervaart et al,4 5 of 6 dogs with LDH had prolonged prothrombin and partial thromboplastin times. A tentative diagnosis can be made on the basis of a dog's history and findings of a physical examination, laboratory evaluations, and diagnostic imaging. Reported ultrasonographic findings for dogs with LDH include ascites, nodular liver processes, abnormal gallbladder walls, and portosystemic collateral pathways.4 In some cases, results of ultrasonographic examinations are normal.4 Definitive diagnosis of LDH requires liver biopsy and histologic examination of tissue sections.
The gross appearance of livers of dogs with LDH can vary depending on the extent of fibrosis and nodular regeneration. In general, the liver is pale and smaller than what would be expected in a healthy dog and has either a relatively smooth surface or smooth areas with variably sized hyperplastic nodules.3 Affected dogs may also have portal vein distension and numerous acquired portosystemic shunts.3,5 Acquired shunts and ascites are presumed to be secondary to portal hypertension.
Histologic changes associated with LDH are characterized by disruption of the normal lobular architecture of the liver by fine collagen and reticulin fibers, which subdivide the parenchyma into single or small groups of hepatocytes.5 The parenchyma is infiltrated by variable numbers of lymphocytes and plasma cells with fewer macrophages and neutrophils, and there can be occasional hepatocyte necrosis.3,5 Regenerative nodules are present in some hepatic lobules.3,5
The etiopathogenesis of LDH is unknown. Infections with certain infectious agents, such as Leptospira spp and canine adenovirus type I, have been proposed as causes of LDH because liver tissue from dogs with those infections have a similar histologic appearance as liver tissue from dogs with LDH, but causation has not been established.2 This condition may reflect a response of the liver to various insults.
Once the diagnosis has been made, the aim of treatment for LDH is to provide supportive care and palliative interventions. Administration of corticosteroids has been reported to be most useful in treatment of idiopathic chronic active hepatitis; however, they have been used in other dogs with chronic hepatitis because of their anti-inflammatory properties.6 Treatment with corticosteroids is thought to reduce the extent and severity of fibrosis through reduction of the release of inflammatory mediators that stimulate hepatic stellate cells.2 Corticosteroids have been used in dogs with LDH, although the efficacy of these drugs is unknown. Additional interventions for dogs with LDH include administration of antioxidants and ursodiol, treatment of ascites by administration of diuretics, and treatment of hepatic encephalopathy when present by provision of a low-protein diet and lactulose.6,7
The prognosis for dogs with chronic hepatitis is variable and depends on the severity of the histopathologic changes. In 1 study, dogs with LDH had significantly shorter survival times, compared with those for dogs with other types of chronic hepatitis; moreover, 7 of 7 dogs in the study4 died of their liver disease. Once cirrhosis is present, the prognosis for long-term survival of dogs with LDH is poor.5,6
References
1. Willard MD. Inflammatory canine hepatic disease. In: Ettinger SJ, Feldman EC, eds. Textbook of veterinary internal medicine. 7th ed. St Louis: Saunders, 2010;1637.
2. Watson PJ. Chronic hepatitis in dogs: a review of current understanding of the aetiology, progression, and treatment. Vet J 2004;167:228–241.
3. Van Den lngh TSGAM, Rothuizen J. Lobular dissecting hepatitis in juvenile and young adult dogs. J Vet Intern Med 1994;8:217–220.
4. Poldervaart JH, Favier RP, Penning LC, et al. Primary hepatitis in dogs: a retrospective review (2002–2006). J Vet Intern Med 2009;23:72–80.
5. Bennett AM, Davies JD, Gaskell CJ, et al. Lobular dissecting hepatitis in the dog. Vet Pathol 1983;20:179–188.
6. Favier RP. Idiopathic hepatitis and cirrhosis in dogs. Vet Clin North Am Small Anim Pract 2009;39:481–488.
7. Rutgers HC, Haywood S. Chronic hepatitis in the dog. J Small Anim Pract 1988;29:679–690.
