Current Concepts

Feline Cholangitis

Inflammatory disease is the second most common cause of hepatobiliary disease in cats. The histological classification of feline inflammatory liver disease is confusing. Terms used in the literature have included suppurative or acute cholangiohepatitis, chronic cholangiohepatitis, chronic lympocytic cholangitis, progressive lymphocytic cholangitis, sclerosing cholangitis, lymphoplasmacytic cholangitis/cholangiohepatitis, lymphocytic portal hepatitis, and biliary cirrhosis. This lack of consistency has made it difficult to compare reported cases. In 2004, the WSAVA Liver Disease and Pathology Standardization Research Group proposed a new classification scheme in order to provide consistency in terminology. Since the group felt that the inflammation was primarily centered on the biliary tree it defined three distinct histopathologic forms of feline cholangitis: 1.) neutrophilic cholangitis (acute and chronic) 2.) lymphocytic cholangitis and 3.) chronic cholangitis associated with biliary fluke infestation. Cats can get true chronic hepatitis but it is rare. Copper toxicity would be one to rule out.

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Innovation

Mesenchymal Stem Cell Therapy for Labrador Retriever Chronic Hepatitis

Labrador retrievers develop a breed-specific chronic hepatitis (CH) that progresses to cirrhosis and hepatic failure. Vague clinical signs include decreased appetite, lethargy, PU/PD and vomiting.  Median age at diagnosis is between 6.4-9.3 years (range: 2-15 years).  A female predominance is noted in some, but not all reports. Dogs typically have increases in serum  ALT and AST with more modest and variable increases in ALP and GGT. Some dogs also have renal tubular disease manifested by the presence of normoglycemic glucosuria. Definitive diagnosis is by hepatic histopathology, which shows varying degrees of necrosis/apoptosis with centrolobular to periportal mononuclear inflammation (lymphocytes, plasma cells and histiocytes), regeneration and fibrosis (Fig 3). In some dogs cirrhosis is present at diagnosis. Median survival is 374 days (range:1-2,645 days).

Fig 3

Figure 3: Hepatic biospy from a 5-year-old spayed female Labrador that presented for anorexia, weight loss, and PU/PD. H and E stains (A, B) show marked portal inflammation consisting of lymphocytes, plasma cells and macrophages. Multifocal lipogranulomas are present. Siruis Red stains (C, D) highlight the abundant fibrosis with prominent bridging between portal areas. Low (A C, 100X)) and high (B, D 400X) power.

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Clinical Case Challenge

A 9-year-old intact male Labrador retriever presented to Tufts Foster Hospital for Small Animals for further evaluation of history of painful gait, chronic atopic dermatitis/pododermatitis (for years) and the recent discovery of of increased liver enzymes (ALT =422 U/L, ALP= 377 U/L, AST =73 U/L) with a normal albumin and bilirubin. The dog had failed to respond to consecutive 3 week courses of clindamycin and cefpodoxime. On physical examination the dog was normal except for extreme difficulty in getting up and walked gingerly. He would not permit full examination of the feet, but a moist dermatitis and areas of ulceration were appreciated (Fig 2 A).

Fig 2

Fig 2. Hepatocutaneous syndrome in a dog. A. Gross appearance of feet with hyperkeratosis and ulceration. B. Ultrasound of liver showing typical ‘honeycomb’ pattern consisting of variable-sized hypoechoic regions surrounded by hyperechoic borders. B. Skin biopsy (H&E) with 1: Marked parakeratotic hyperkeratosis; 2: Vacuolar change in the upper levels of the epidermis; 3. Hyperplastic epidermis with acanthosis. Images A and C courtesy of Dr Lluis Ferrer and B from Dr. Dominique Penninck.

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At Your Service

An Interdisciplinary Team Approach to Hepatobiliary Disease

At the Tufts Foster Hospital for Small Animals at the Cummings School Veterinary Medicine, we rely heavily on a talented team of veterinary specialists to help treat small animals with hepatobiliary disease.  Often times, diagnosing hepatobiliary disease is a complicated process given the liver’s wide-ranging role in digestion, intermediary metabolism and biotransformation. Additionally, the liver is sensitive to secondary injury from many systemic disorders as well.

The diagnosis of hepatobiliary disease often requires expert diagnostic imaging (ultrasound and scintigraphy) as well as histopathologic interpretation of hepatic biopsy material.

Tufts Foster Hospital for Small Animals is fortunate to have Dr. Dominque Penninck, one of the pioneers of hepatobiliary ultrasound, on staff. He is joined by pathologists, Dr. Sam Jennings, who trained with the world renowned veterinary hepatic pathologist Dr. John Cullen, and Dr. Arlen Rogers, whose research interests include animals models of hepatic cancer.

Both of our soft tissue surgeons, Dr. Ray Kudej and Dr. John Berg, have interests in  hepatobiliary and portovascular surgery.

Our cardiologist, Dr. John Rush, is also available to manage intrahepatic shunts with interventional radiology.  These individuals are complemented by a skilled group of board certified anesthesiologists who often help us with the complicated management of our critically ill patients with hepatobiliary disease.

Lastly, we have a team of nutritionists, including Dr. Lisa Freeman and Dr. Calin Heinze, who help us meet the dietary requirement of our patients.  Some nutrients that could be of concern often include sodium, copper and/or protein balance. In addition, many hepatobiliary patients have a need for the placement of enteral nutrition tubes and occasionally formulation of balanced homemade diets.

Cynthia RL Webster, DVM, DACVIM (Small Animal Internal Medicine)
Professor, Associate Chair
DACVIM (Internal Medicine)
Post-Doctorate, Tufts Medical School, Department Physiology 1991-1993
DVM – Cornell University – 1985
BS – Simmons College – 1978

Dominique Penninck, DVM, ACVR
Professor
PhD – University of Liege, Belgium
DVM – University of Liege, Belgium
Diplomate, American College of Veterinary Radiology
Diplomate European College of Veterinary Diagnostic Imaging

Sam Jennings, DVM, ACVP
Assistant Professor
DVM – Tufts University Cummings School of Veterinary Medicine
MSpVM – North Carolina State University
American College of Veterinary Pathologists (Anatomic Pathology)

Arlen Rogers, DVM, Ph D, ACVP

John Berg, DVM, ACVS
Professor
Soft Tissue Surgery
MS – Colorado State University
DVM – Colorado State University
Board certification: ACVS

Ray Kudej, DVM, ACVS
Associate Professor
Soft Tissue Surgery
Post-Doctorate – Harvard Medical School
PhD – Iowa State University
DVM – Iowa State University
Board certification: ACVS

Lisa Freeman
Nutrition
PhD – Tufts University School of Nutrition
DVM with thesis – Tufts University School of Veterinary Medicine
BS – Tufts University
Board Certification:  American College of Veterinary Nutrition

Calin Heinze
Nutrition
Assistant Professor, Nutrition
MS – Nutritional Biology – University of California, Davis
VMD – University of Pennsylvania School of Veterinary Medicine
Board Certification: American College of Veterinary Nutrition (ACVN)

Lluis Ferrer, DVM, DACVD, PhD
Dermatology
Professor, Dermatology
DVM – Universidad de Zaragoza, Spain, 1981
PhD – Universidad de Zaragoza, Spain, 1985
Board certification – ECVD, 1995

John Rush
Interventional Radiology (IH Shunts)
Professor
Cardiology
DVM – Ohio State University
MS – Ohio State University
Board Certification Cardiology (ACVIM) and (ACVECC)