A case of chronic active hepatitis complicated by PPID and hydatidosis

Blood samples, ultrasound and liver biopsies are useful diagnostic tools for hepatic disease

07 December 2020, at 8:30am

Hepatic disease is common in horses, often having multiple aetiologies. This report details the investigation and treatment of a novel case of chronic active hepatitis (CAH) complicated by concurrent hydatidosis and pituitary pars intermedia dysfunction (PPID).

Case history and clinical examination

An aged crossbred pony mare presented with acute weight loss (60kg by weight tape). The animal had been routinely vaccinated and regularly dewormed, and was undergoing treatment for PPID with 1mg q24hr PO pergolide mesylate. At initial examination, body condition was assessed as 3/9 and was otherwise unremarkable. Peripheral blood and faecal samples showed a regenerative anaemia (Hct 24.7%, MCV 55ƒl), with elevations in γ-glutamyl transferase (GGT 121 IU/l), lactate dehydrogenase (LDH 548 IU/l) and glutamyl dehydrogenase (GlDH 14 IU/l). Dietary intake was deemed adequate but increased by 25 percent to 44MJ.

Three weeks later, further weight loss (40kg by weight tape) had occurred. The animal was hospitalised for further investigation.

Clinical investigation

On admission, an indwelling jugular intravenous catheter was placed using aseptic technique. A fasted blood sample showed elevations in GGT (80 IU/l), LDH (542 IU/l), GlDH (21.3 IU/l), creatinine kinase (CK 445 IU/l), adrenocorticotropic hormone (ACTH 51.9ρg/l) and β2 globulins. Urinalysis was unremarkable. An oral glucose tolerance test (OGTT) was performed to establish small intestinal function, and the results were equivocal.

Trans-abdominal ultrasound (Vivid 5, 1.6 to 3.6 MHz phased array probe–GE) showed the liver had numerous small choleliths, dilated bile ducts and periportal hyperechogenicity (Figures 1A and 1B). Numerous spherical cavitated lesions approximately 5cm in diameter were evident throughout the examinable liver (Figures 1B and 1C). These were highly suggestive of hydatid cysts (Blanton et al., 1998). Abdominocentesis yielded normal peritoneal fluid with a total protein of 15g/dl and a nucleated cell count of 0.6x109/l (macrophages and mature lymphocytes).

After establishing normal clotting function, needle biopsy of the liver was performed using ultrasound guidance following aseptic preparation of the right 14th and 15th intercostal spaces. Histopathology analysis showed hepatocyte cytoplasmic swelling (Figure 2A), periportal infiltration of neutrophils, lymphocytes and haemosiderophages (Figure 2B) and moderate fibrosis (Figure 3). Bacterial culture was unremarkable. These findings were consistent with CAH/cholangitis. A guarded prognosis was given.

FIGURE (3) A histomicrograph using Van Gieson’s stain showed periportal fibrosis (collagen appears red in colour)
FIGURE (3) A histomicrograph using Van Gieson’s stain showed periportal fibrosis (collagen appears red in colour)

Due to a possible bacterial aetiology, 10mg/kg doxycycline (Karidox-Nimrod) per os q12hr was given for 10 weeks. The hydatid cysts were treated with 8mg/kg albendazole per os q12hr for 21 days, and the pergolide mesylate dosage was increased to 1mg BID. A low protein (less than 15 percent crude protein), low aromatic/high branched chain amine, high carbohydrate diet was introduced, providing 150 percent of calculated daily energy requirements (62 MJ), and supplemented with a dietary antioxidant.

Re-examination 12 weeks later demonstrated further weight gain assessed at 80kg with all clinical parameters within normal limits. Analysis of a peripheral blood sample showed a mild regenerative anaemia (MCV 57ƒl, Hct 32.6%), and elevated but declining CK, LDH, GGT and GlDH. Ultrasound examination of the liver showed no visible hydatid cysts or choleliths, and a reduction in biliary distension. Biopsy was not repeated at the request of the owner.

Subsequent re-examination showed the horse to be maintaining body condition, but a guarded prognosis was given.


Hepatic pathology in horses is relatively common, and multiple hepatic pathological processes may occur simultaneously (Barton, 2004). Ponies are more likely to develop hepatic disease than horses, but age and gender are not significant risk factors. Clinical signs of hepatic disease are often vague but commonly include weight loss, polydipsia, peripheral oedema, anorexia, diarrhoea, neurological disturbance, abdominal pain and photosensitisation (Smith et al., 2003).

CAH is characterised by periportal necrosis, biliary hyperplasia and fibrosis. Causes include immune-mediated diseases (Pearson, 1990) and ascending biliary tract infections (Carlson, 1981; Barton, 2004). PPID has been implicated in immunosuppression and increased hepatic catabolic loading (Toribo, 2004), and is likely in this case. Hydatidosis is caused by various Echinococcus taxa metacestodes, but only E. equinus is known to produce fertile cysts taking 6 to 12 months to develop, and is ubiquitous in Great Britain (Urquhart et al., 1987). Clinical signs derived from hydatid disease are rare, but it is a common post-mortem diagnosis (Edwards, 1982). Hepatic hydatid cysts rarely disrupt sufficient hepatic stroma to show clinical signs; however, the large numbers of hydatids in this case may have contributed to the hepatic dysfunction. The horse in this case had access to moorland pasture and therefore exposure to untreated wild canids, which are more likely to be infected with the adult cestode.

Hepatic disease requires differentiation from other causes of weight loss with specific laboratory and functional testing. An OGTT was used as a proxy for small intestinal function: adequate absorption is an increase of 85 percent from basal blood glucose, and malabsorption as less than 15 percent increase from basal (Mair et al., 1991). In this case, OGTT indicated partial malabsorption but cortisol-induced insulin insensitivity (PPID) may have affected the result (Toribo, 2004). An oral xylose absorption test may have attenuated this (Roberts, 2000) but current difficulty in sourcing xylose precluded its use.

Peripheral blood samples can indicate liver disease by the release of cytosolic enzymes due to cellular injury or alterations in the hepatic/blood barrier. However, dependence on these assays exclusively for prediction of or absence of clinical hepatic disease may lead to diagnostic error.

Ultrasound is a safe non-invasive procedure but limited in the horse by superimposition of the diaphragm, lungs, viscera and ribs. In this case, the liver was acoustically heterogenic with small choleliths, dilated bile ducts and increased periportal echodensity evident. Whilst not diagnostic of CAH, they are suggestive of periportal and biliary disease consistent with cholangiohepatitis or CAH (Carlson, 1989). Choleliths with bacteria acting as a nidus for crystal deposition was considered likely (Barton, 2004), but are frequently reported as an incidental finding (Johnston et al., 1989). The spherical cavitated lesions equate acoustically to the hydatid cysts described by Blanton et al. (1998). Ultrasound was used to select biopsy sites not invested with hydatids to prevent coelomic dissemination.

Liver biopsy is essential for the diagnosis of chronic liver disease, and allows assessment of hepatic architecture, fibrosis and cell population (Durham et al., 2003). This technique is well tolerated in the standing sedated horse and few problems have been reported (West, 1998; McGorum et al., 1999).

Albendazole is the only available therapy for horses with hydatidosis (Urquhart et al, 1987). In humans, radical surgery to remove cysts alongside long-term albendazole therapy is recommended (Gottstein, 2000). Doxycyline was selected for its lipophilicity, broad spectrum of activity and amphotericity. Supportive care using dietary antioxidants and a low protein diet to reduce oxidative and metabolic stress was used as suggested by Divers (1990).

No reports of survival rates for CAH are in the literature. In a retrospective study of equine hepatic disease, Smith et al. (2003) found fatality rates lower than expected. Horses with hepatopathies with no specific diagnosis were shown to have lower fatality rates than those with cholangiohepatitis, pyrrolizidine alkaloid toxicity and chronic active hepatitis. Despite a favourable response to treatment in this case, the prognosis for long-term survival must remain guarded.

Author Year Title
Barton, M. H. 2004 Disorders of the liver. In: Reed, S. M., Bayly, W. M. and Sellon, D. C. (eds) Equine Internal Medicine Vol 2. Saunders, St Louis, 951-994
Blanton, R. E., Wachira, T. M., Zeyhle, E. E., Njoroge, E. M., Magambo, J. K. and Schantz, P. M. 1998 Oxfendazole treatment for cystic hydatid disease in naturally infected animals. Antimicrobial Agents and Chemotherapy, 42, 601-605
Carlson G. P. 1989 Chronic active hepatitis in horses. Proceedings of the seventh annual forum of the American College of Veterinary Internal Medicine. San Diego, 595
Divers, T. J. 1990 Therapy of liver failure. In: Smith, B. P. (ed) Large Animal Internal Medicine. Mosby, St Louis
Durham, A. E., Smith, K. C. and Newton, J. R. 2010 An evaluation of diagnostic data in comparison to the results of liver biopsies in mature horses. Equine Veterinary Journal, 35, 554-559
Edwards, G. 1982 Observations on the epidemiology of equine hydatidosis in Britain. Veterinary Record, 110, 511-514
Gottstein, B. 2000 Epidemiology and systematics of cystic and alveolar hydatid disease. Der Chirurg, 71, 0001-0008
Johnston, J. K., Divers, T. J., Reef, V. B. and Acland, H. 1989 Cholelithiasis in horses: ten cases (1982-1986). Journal of the American Veterinary Medical Association, 194, 405-409
Mair T. S., Hillyer, M. H. and Taylor F. G. 1991 Small intestinal malabsorption in horses. Equine Veterinary Journal, 23, 344-346
McGorum, B. C., Murphy, D., Love, S. and Milne, E. M. 1999 Clinicopathological features of equine primary hepatic disease: a review of 50 cases. Veterinary Record, 145, 134-139
Pearson, E. G. 1990 Chronic active hepatitis. In: Smith, B. P. (ed) Large Animal Internal Medicine, Mosby, St Louis
Roberts, M. C. 2000 Small intestinal malabsorption in horses. Equine Veterinary Education, 12, 214-219
Rose, R. J. and Hodgson, D. R. 1999 Manual of Equine Practice. 2nd Edition. Saunders, St Louis
Smith, M. R., Stevens, K. B., Durham, A. E. and Marr, C. M. 2003 Equine hepatic disease: the effect of patient- and case-specific variables on risk and prognosis. Equine Veterinary Journal, 35, 549-52
Toribo, R. 2004 Cushing’s disease. In: Reed, S. M., Bayly, W. M. and Sellon, D. C. (eds) Equine Internal Medicine, volume 2. Saunders, St Louis, 951-994
Urquhart, G. M., Armour, J., Duncan, J. L., Dunn, A. M. and Jennings F. W. (eds) 1987 Veterinary Parasitology. Longman Scientific and Technical, Harlow, 123-125
West, H. 1996 Clinical and pathological studies in horses with hepatic disease. Equine Veterinary Journal, 28, 146

Jamie Wallace graduated from Glasgow Vet School in 1998. He has worked in equine practice since 2000 attaining the ESVPS CertEP and the RCVS CertEM(IntMed) and currently works at MBM Veterinary Group, part of IVC Evidensia. His main interests are internal medicine, ophthalmology and oncology.

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