Beagle’s Journey Sheds Light on Rare Form of Hepatitis in New Research from Cummings School

Over a ten year span only 29 patients with granulomatous hepatitis (GH) walked through the doors of Henry and Lois Foster Hospital for Small Animals (FHSA) at Cummings School of Veterinary Medicine at Tufts University. The disease is so uncommon that very little is published about its presentation, symptoms, and best treatment options. A Beagle named Sasha became a key subject in the largest study of dogs with this rare form of chronic hepatitis.

The research project was initiated by Dr. Cynthia Webster (she/her) on the Internal Medicine Team at FHSA and professor in the Department of Clinical Sciences at Cummings School when she started tracking commonalities among her GH patients.

“Being a hepatologist for 30 years, I noticed that dogs with granulomatous hepatitis present a little differently and we needed to get together cases to better understand the disease process,” says Webster.

She gathered a team at FHSA to launch a retrospective observational study of all the GH cases treated at FHSA over the past decade. The research paper, “Characterization of clinical presentation, histological features, ultrasonographic findings, and survival in 29 dogs with granulomatous hepatitis,” was published in the January-February 2024 issue of the Journal of Internal Veterinary Medicine.

Sasha became a part of the study when her owner, Dr. Carla DiGirolamo, became concerned that her normally rambunctious two-year-old Beagle was not eating well and had less energy.

“Sasha’s personality is as big as life, she was absolutely the alpha dog of the litter. She has two generations of hunting champions in her pedigree, so her prey drive is unbelievable. We noticed the difference immediately when she was lethargic,” DiGirolamo says. “I can thank Cummings School for saving her life twice during two life-threatening episodes.”

During Sasha’s initial visit, she was diagnosed with GH, a disease that involves granulomas, or the accumulation of a specific type of inflammatory cell called macrophages, in the liver. Her condition resolved with antibiotics, and her case was added to the study. Sasha was healthy for the next four years until she relapsed and returned to FHSA with even more pronounced symptoms and a high fever.

This time, Sasha did not respond to antibiotics, but corticosteroids and other immunosuppressants were effective in treating her GH. Several months later, when Sasha had been weaned off corticosteroids she returned a third time to FHSA again with symptoms of her liver disease.

“Dr. Webster jumped in and saved her again. I don’t know how many times her liver can handle a relapse. Dr. Webster got her in quickly and got her back on track,” recalls DiGirolamo. Webster restarted Sasha on a low dose of corticosteroids, returning her to health.

The lead author of the study, Dr. Kayla Prentice, V21 (she/her), a small animal internal medicine resident at FHSA, met Sasha for the first time last summer during a recheck visit.

“I had known of Sasha’s case through the data from the GH study I was working on, I knew all these dogs front and back,” says Prentice. “It’s neat to put a face to the name and rewarding to see how well she has responded.”

Prentice was a student at Cummings School when she and Webster started the study. Up until that point, most of the previous research into GH in dogs had been focused on possible infectious causes, although in the human literature GH can be associated with other causes, including autoimmune disease.

“There’s not a plethora of research about this particular flavor of hepatitis in dogs, and there was some thought that these dogs perhaps had an infectious disease that was hard to diagnose,” says Prentice.

In addition to Prentice, Webster also pulled in other clinicians for the study, including Dr. Julie Callahan-Clark, V07, Dr. Nicola Parry, pathologist at FHSA, and Dr. Leslie Schwarz, an ultrasonographer, to help discover commonalities among patients with GH in terms of symptoms, presentation, treatment, and survival rates.

“We found out that GH presents differently than normal with dogs with chronic hepatitis. It comes on quicker, they are sicker when they present, and there’s often a fever,” says Webster. “Ours is the only paper that talks about what they respond to, really the first paper to look at treatment.”

In reviewing the 29 patients’ ultrasounds, Schwarz found three indicators that could suggest GH: enlarged liver, nodules in the liver, and lesions around the blood vessels in the liver. In some cases the ultrasound finding might be reminiscent of liver cancer. Parry examined the patients’ biopsies and determined that GH cases presented with more active disease early on, before much scarring.

“In some cases, based on the symptoms and the ultrasound imaging, we thought the dogs had cancer. Three or four of these dogs I thought would have cancer and was worried they would have a very bad prognosis, but they turned out to have GH. These dogs are happy, healthy, and wagging their tails today,” says Webster.

The study recommends treating GH with immunosuppressants after common infectious diseases are eliminated. Many dogs in the study, including Sasha, responded well to immunosuppressants and have had long survival times.

“As a new vet, in the future when I have cases of granulomatous hepatitis in dogs, if they’re not responding to antibiotic therapy, I will more quickly recommend immunosuppressants than before. It’s already influencing how I’m treating these cases,” says Prentice.

On the relevance of the study, Webster says, “I’ve had 190 publications, this is one of the more impactful publications that’s out there.”

The study will also be featured in a chapter written by Prentice and Webster in the upcoming edition of Veterinary Clinics of North America: Small Animal Practice.

Much is still unknown about GH, and Webster hopes to one day do a multi-institutional study that will enroll cases all over the country looking at possible causes of the disease—infectious and noninfectious—by region.

Sasha went into remission last June. Now seven, Sasha has been tapered to a low dose of immunosuppressants and is going strong, her liver functioning normally. The family moved to Florida for the winter, and DiGirolamo keeps in regular communication with Prentice and Webster on Sasha’s health and bloodwork.

“Sasha’s back to herself, even more adept at catching animals now than ever,” says DiGirolamo, who notes that Sasha’s new favorite prey are lizards. “Dr. Prentice and Dr. Webster have been wonderful. I am so grateful for their care and compassion and that they still continue to be interested in her case. We love this dog so much.”

Prentice additionally credits Sasha’s recovery to the dog’s resilience and her family’s dedication.

“It’s really rewarding seeing that prolonged improvement, despite having gone through a long journey with her liver,” says Prentice. “Our research and anecdotal experience helped her. This is the first step to better understanding this condition. The new recommendation is that immunosuppression can work in these dogs. Sasha was one that helped prove that.”