Degenerative Vacuolar Hepatopathy

 

By: Rebecca Norton, DVM, DACVIM

Signalment:

11 y FS Miniature Schnauzer

History:

Mulligan was referred to GCVS Internal Medicine for further evaluation of elevated liver enzymes (ALP>ALT) for 1-2 years. Typically she is playful and active with a normal appetite. She has intermittent diarrhea, sometimes with blood, that resolves with symptomatic care. She previously had elevated triglycerides (5000), but this has resolved.

Physical Exam:

Mulligan was bright and alert. Her gums were pink, and she was nicely hydrated. Her heart and lungs sounded normal, and her abdomen was soft and not painful. She was in good body condition. She had a soft fluctuant subcutaneous mass on her left thoracic wall. She had a dark 2-3 mm raised mass on her mid-dorsum (history of melanocytic tumors).

Diagnostics:

CBC: HCT 40%, WBC 6.35K, Plts 583K
Chemistry panel: ALT 307 U/L, ALP 715 U/L, tBili 2.7 mg/dL, Albumin 4.0 g/dL, Globulin 5.4 g/dL (Total Protein 9.4 g/dL)
Urinalysis USG 1.040, 3+ protein, otherwise quiet sediment
PT 5.4s
PTT 9.4s
ACTH stimulation test: Pre cortisol 1.0 mg/dL, post cortisol 15.6 mg/dL
An abdominal ultrasound was performed. Only abnormalities will be discussed.
There is decreased corticomedullary definition bilaterally and the renal cortices are hyperechoic. The caudal pole of the left adrenal and the cranial pole of the right adrenal gland each contain a single hyperechoic focus. Punctate hyperechoic foci are present in the body of the spleen and a single hypoechoic nodule is identified (0.28cmx35cm). Irregularly marginated hyperechoic nodules, consistent with myelolipomas, are present along the splenic border. The liver is diffusely heterogeneous and contains hyperechoic nodules ranging from 0.2-0.42cm. Punctate hyperechoic foci are also present throughout the liver. The left pancreas is heterogeneous with hyperechoic regions in the parenchyma, yet the adjacent mesentery is normal.

Conclusions
  • Fibrosis of the left limb of the pancreas is suspected.
  • Chronic renal degenerative changes, characterized by cortical fibrosis.
  • Punctate dystrophic mineralization within the spleen, liver, and adrenal glands. This finding may be secondary to hypercalcemia, hyperadrenocorticism, or exogenous steroid administration.
  • Nodular regeneration associated with hepatopathy is suspected.
  • The splenic nodule may be secondary to extramedullary hematopoeisis or lymphoid hyperplasia.
  • Liver histopathology: Glycogen type vacuolar hepatopathy, severe, diffuse, degenerative
  • Examined are 3 small fragments of liver with moderate crush artifact. Hepatocytes are diffusely distended with numerous, variably sized, rough-bordered vacuoles separated by thin wisps of cytoplasmic that extend from the cell membrane to the nucleus and are filled with eosinophilic, homogeneous material, compatible with glycogen-type vacuolar hepatopathy. Clusters of several dozen hepatocytes with no obvious zonal tropism display severe ballooning degeneration. Portal tracts are infiltrated by varying proportions of mixed myeloid and erythroid extramedullary hematopoiesis. Small to moderate numbers of hemosiderin laden macrophages accompany the extramedullary hematopoiesis. Due to sub-optimal sample preservation, portal tracts are extremely difficult to discern. However, they appear to be irregularly expanded by small amounts of fibrous connective tissue. Bile ducts within the portal tracts are often disorganized, which may indicate either mild biliary hyperplasia or a mild ductular reaction.
  • A panel of histochemical stains was assessed to better characterize liver architecture (reticulin), fibrosis (Masson’s trichrome) and heavy metal accumulation (Prussian blue for iron and Rhodanine for copper).

Reticulin: The reticulin stain highlights irregular expansion of portal tracts due to the accumulation of extracellular matrix. The adventitia around central veins is mildly expanded. No parenchymal collapse, parenchymal extinction or foci of proliferative hepatocytes are discerned.

Mason’s trichrome (type I collagen): The trichrome stain confirms and emphasizes extensive glycogen-type vacuolar hepatopathy. Hepatocytes in centrilobular and mid zonal regions are more severely affected and often have groups of several 100 hepatocytes with severe distention of the cytoplasm. The trichrome stain provides further confirmation of irregular expansion of portal tracts due to the accumulation of fibrillar collagen. No bridging or dissecting fibrosis is detected. The enhance contrast provided by the trichrome stain can accentuate necrotic hepatocytes; none are observed. No evidence of cholestasis is detected. Small nodular foci of mixed myeloid and erythroid extramedullary hematopoiesis are in portal tracts, cuff central veins and randomly dispersed in the parenchyma.

Prussian blue (iron): The Prussian blue confirms small clusters in individual macrophages in portal tracts contain moderate to occasionally large amounts of iron. Less than one third of Kupffer cells contain a scant amount of iron. Hepatocytes are devoid of stainable iron.

Rhodanine (copper): The rhodanine stain demonstrates rare hepatocytes with moderate numbers of coarse copper granules. These results correspond to a grade 1 out of 5 on a semiquantitative scale where grade 0 indicates no stainable copper and grade 5 corresponds to pan lobular copper accumulation. Copper quantification 331 ppm (normal 120-400 ppm, deficient < 80 ppm, toxic > 1500 ppm)

Liver cultures (anaerobic/aerobic) negative for bacterial growth

summary:

Mulligan’s biopsy report is consistent with Degenerative Vacuolar Hepatopathy. There was no significant inflammation, scar tissue (fibrosis), or copper accumulation, and the cultures submitted were negative. A small proportion of dogs diagnosed with Degenerative Vacuolar Hepatopathy will develop progression of the lesions, acquired shunts, liver failure, or hepatocellular carcinoma. At the time of diagnosis, no specific treatment is indicated due to the lack of inflammation or fibrosis seen on histopathology.

treatment:

Supportive anti-oxidant treatment with Milk Thistle, SAMe, and Vitamin E is indicated.

monitoring:

  • Lab and ultrasound monitoring of the liver is recommended every 3 months.