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 (Figure 1). 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 0.6×109/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.
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.
Discussion
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.
