Liver / Hepatic Disorders of the
Cavalier King Charles Spaniel

The predominance of disorders of the canine liver appear to vary depending upon the breed. The most common liver disorder in dogs is chronic hepatitis. Overall, the cavalier King Charles spaniel does not stand out as having a higher incidence of any form of hepatitis, hepatic cancer, of other severe disorders involving the liver.

Below is a listing of liver disorders of which the CKCS tends to be predisposed. 

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List of Disorders

The disorders include:

Hepatic lesions

Liver lesions are groups of abnormal cells in the dog's liver. They occur as a result of any of a variety of hepatic diseases which involve inflammation of the liver. Canine hepatic diseases are divided into two main types: primary and secondary. "Primary" means that the liver is directly affected by the disorder and consists of chronic hepatitis, acute hepatitis, fibrosis, cirrhosis, and neoplasia. "Secondary" means that the disorder is ancillary to some other bodily disorder and consist of hepatic congestion, hepatic vacuolation, and reactive hepatitis.

In a January 2016 article about the prevalence of hepatic lesions in cavalier King Charles spaniels, the livers of 54 deceased CKCSs were examined. Of those, 13 were found to have no liver disorders, and the remaining 41 had hepatic lesions associated with a combined total of 7 liver disorders. Only two of the cavaliers had been diagnosed with hepatic disorders prior to their deaths. The breakdown of hepatic disorders appears on the study's Table 3 below.

Table 3 

Secondary hepatic lesions were detected in 64.8% of the cavaliers in the study, while only 11.1% of them had primary hepatic lesions. The investigators stated:

"Hepatic lesions were commonly detected in this study, but the majority of cases were diagnosed as secondary to other diseases. For instance, congestion was assumed to be related to chronic heart disease. Although this supposition was not supported by the relative risk statistics, the sample size was small, and the power to detect these associations was weak. The finding of hepatocyte vacuolation is likely to be a secondary reactive change of the liver to a variety of other diseases."
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Hepatic mineralization

Hepatic mineralization describes the appearance of mineral "opacities" in any of a variety of patterns in the liver in x-rays. In a December 2017 article, its researchers assessed the prevalence and clinical significance of linear branching mineralization of dogs' livers on x-rays from one referral veterinary hospital over a period off 30 years. They report that of 17 dogs with branching mineralization in their livers, 7 (41%) were cavalier King Charles spaniels. While they found that the prevalence of branching hepatic mineralisation in dogs appears to be very low, the CKCS was "over-represented" in the study and have an increased prevalence compared with other breeds or crossbreed dogs, since they accounted for only 5.2% of dogs seen at the hospital and only 4.1% of x-rays which included the liver.

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Portosystemic (liver) shunt

In a normal dog, blood from the gastrointestinal tract enters the portal vein, which then takes blood to the liver, which then metabolizes and detoxifies this blood before sending it back into the circulatory system to the heart. A portosystemic shunt is a blood vessel present at the fetal stage, carrying toxified blood directly from the gastrointestinal tract to the heart, bypassing the liver and shunting the blood directly into the circulatory system. These shunts are classified as either intrahepatic (inside the liver) and extrahepatic (outside the liver) shunts. An intrahepatic portosystemic shunt represents a normal embryologic shunt which normally closes at birth, allowing the liver to take over its filtering, storage, and production functions. However, in some cases the intrahepatic shunt does not close down properly and the liver is unable to grow or function properly. An extrahepatic portosystemic shunt (EHPSS) is an abnormal embryonic connection between to venous systems, which completely bypasses the liver. Most portosystemic shunts are congenital, but in some cases, shunts may be acquired due to another problem with the liver.

Yorkshire terriers and Cairn terriers reportedly appear to have an inherited basis for  extrahepatic portosystemic shunts (EHPSS). Breeds are predisposed to EHPSS are Jack Russell terriers, Dachshunds, Miniature schnauzers, and Maltese. EHPSS have been observed mainly in small breeds. Cavaliers do not appear to be predisposed to EHPSS, but some CKCSs have been diagnosed with the disorder. See this July 2012 article and this December 2015 article and this November 2017 article for additional information regarding cavaliers with this condition.

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Research News

December 2017: Cavaliers are "over-represented" in a study of hepatic mineralization. Hepatic mineralization describes the appearance of mineral "opacities" in any of a variety of patterns in the liver in x-rays. In a December 2017 article, its researchers (M.-A. Genain, A. Barbosa, M. Herrtage, P. Watson)  assessed the prevalence and clinical significance of linear branching mineralization of dogs' livers on x-rays from one referral veterinary hospital over a period off 30 years. They report that of 17 dogs with branching mineralization in their livers, 7 (41%) were cavalier King Charles spaniels. While they found that the prevalence of branching hepatic mineralisation in dogs appears to be very low, the CKCS was "over-represented" in the study and have an increased prevalence compared with other breeds or crossbreed dogs, since they accounted for only 5.2% of dogs seen at the hospital and only 4.1% of x-rays which included the liver.

January 2016: Secondary hepatic lesions were found in 64.8% of post-mortem samples of cavaliers in UK study. In a January 2016 article, UK researchers (Kent, Andrew C. C.; Constantino-Casas, Fernando; Rusbridge, Clare; Corcoran, Brendan; Carter, Margaret; Ledger, Tania; Watson, Penny J.) searched for pancreatic, hepatic (liver) and renal (kidney) lesions in post-mortem samples from Cavalier King Charles Spaniels (CKCSs). Primary hepatic lesions were present in only 11.1% of cases, but secondary hepatic lesions were more common and were present in 64.8%. The researchers report that cavaliers have similar rates of hepatic disease as the general population.

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Related Link

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Veterinary Resources

Control of Canine Genetic Diseases. Padgett. G.A., Howell Book House 1998, pp. 198-199, 222.

Distribution of extrahepatic congenital portosystemic shunt morphology in predisposed dog breeds. Lindsay Van den Bossche, Frank G van Steenbeek, Robert P Favier, Anne Kummeling, Peter AJ Leegwater, Jan Rothuizen. BMC Vet. Research. July 2012;8:112. Quote: "Background: An inherited basis for congenital extrahepatic portosystemic shunts (EHPSS) has been demonstrated in several small dog breeds. If in general both portocaval and porto-azygous shunts occur in breeds predisposed to portosystemic shunts then this could indicate a common genetic background. This study was performed to determine the distribution of extrahepatic portocaval and porto-azygous shunts in purebred dog populations. Results: Data of 135 client owned dogs diagnosed with EHPSS at the Faculty of Veterinary Medicine of Utrecht University from 2001 – 2010 were retrospectively analyzed. The correlation between shunt localization, sex, age, dog size and breed were studied. The study group consisted of 54 males and 81 females from 24 breeds. ... Additional breeds diagnosed with EHPSS were the Lhasa Apso, Miniature Poodle, Norfolk terrier with two cases, and single cases of a Basset Hound, Bolognese, Cavalier King Charles Spaniel, Epagneul Nain Papillon, Flat Coated Retriever, Fox terrier, Giant Spitz, Great Dane, Miniature Pinscher, Norwich terrier and Welsh terrier. ... Twenty-five percent of dogs had porto-azygous shunts and 75% had portocaval shunts. Of the dogs with porto-azygous shunts only 27% was male (P = 0.006). No significant sex difference was detected in dogs with a portocaval shunt. Both phenotypes were present in almost all breeds represented with more than six cases. Small dogs are mostly diagnosed with portocaval shunts (79%) whereas both types are detected. The age at diagnosis in dogs with porto-azygous shunts was significantly higher than that of dogs with portocaval shunts (P < 0.001). Conclusion: The remarkable similarity of phenotypic variation in many dog breeds may indicate common underlying genes responsible for EHPSS across breeds. The subtype of EHPSS could be determined by a minor genetic component or modulating factors during embryonic development."

A Retrospective Histopathological Survey on Canine and Feline Liver Diseases at the University of Tokyo between 2006 and 2012. Naoki Hirose, Kazuyuki Uchida, Hideyuki Kanemoto, Koichi Ohno, James K. Chambers, Hiroyuki Nakayama. J. Vet. Med. Sci. July 2014;76(7): 1015–1020. Quote: "To determine the incidence of hepatic diseases in dogs and cats in Japan, a retrospective study was performed using data of 463 canine and 71 feline liver biopsies at the Veterinary Medical Center of the University of Tokyo. The most common canine hepatic disease was microvascular dysplasia (MVD) and occupied 29.4% of all diagnoses. This terminology might contain “real” MVD and primary portal vein hypoplasia, because these two conditions were difficult to be clearly distinguished histopathologically. Parenchymal and interstitial hepatitis and primary hepatic tumors accounted for 23.5% and 21.0% of the diagnoses, respectively. Parenchymal and interstitial hepatitis occupied 34.1% of non-proliferative canine hepatic diseases, while hepatocellular adenoma and carcinoma were 26.6% and 24.5% of roliferative hepatic diseases, respectively. Breed-specificity was seen in MVD for Yorkshire terrier, Papillon and Toy poodle, in hepatitis for Doberman pinscher and Labrador retriever, in cholangiohepatitis for American cocker spaniel, Miniature schnauzer and Pomeranian, in hepatocellular adenoma for Golden retriever and Shiba and in hepatocellular carcinoma for Shih Tzu. Among 25 cases of canine chronic hepatitis, Labrador retrievers and Doberman Pinschers ranked the first (8 cases, 32.0%) and the second (3 cases, 12.0%), respectively. Females were more susceptible than males in both breeds [Labrador retrievers (male/female=1:7) and Doberman pinschers (male/female=1:2)]. The median age of the hepatitis cases was 8 years and 7 months old. Eight of the 25 canine chronic hepatitis cases had copper deposition. Two of the 8 cases were Doberman pinschers, and 1 was Labrador retriever, Bedlington terrier, Welsh corgi, Cavalier King Charles spaniel or a mixed breed."

Lipopolysaccharide and toll-like receptor 4 in dogs with congenital portosystemic shunts. M.S. Tivers, V.J. Lipscomb, K.C. Smith, C.P.D. Wheeler-Jones, A.K. House. Vet. J. December 2015;404-2015;206(3):303-413. Quote: "Surgical attenuation of a congenital portosystemic shunt (CPSS) results in increased portal vein perfusion, liver growth and clinical improvement. Portal lipopolysaccharide (LPS) is implicated in liver regeneration via toll-like receptor (TLR) 4 mediated cytokine activation. The aim of this study was to investigate factors associated with LPS in dogs with CPSS. Plasma LPS concentrations were measured in the peripheral and portal blood using a limulus amoebocyte lysate (LAL) assay. ... We included paired peripheral and portal plasma samples from 13 CPSS dogs of the following breeds: Bichon Frise (n = 2), Labrador (n = 2), Border terrier (n = 1), Cavalier King Charles spaniel (n = 1), crossbreed (n = 1), Dogue de Bordeaux (n = 1), German shepherd dog (n = 1), Miniature Schnauzer (n = 1), Springer spaniel (n = 1), West Highland White terrier (n = 1), Yorkshire terrier (n = 1). The median age was 295 days (range, 125–1835 days). Nine dogs (69.2%) had an extrahepatic CPSS and four (30.8%) had an intrahepatic CPSS. ... LPS concentration was significantly greater in the portal blood compared to peripheral blood in dogs with CPSS (P = 0.046) and control dogs (P = 0.002). LPS concentrations in the peripheral (P = 0.012) and portal (P = 0.005) blood of dogs with CPSS were significantly greater than those of control dogs. The relative mRNA expression of cytokines and TLRs was measured in liver biopsies from dogs with CPSS using quantitative PCR. TLR4 expression significantly increased following partial CPSS attenuation (P = 0.020). TLR4 expression was significantly greater in dogs that tolerated complete CPSS attenuation (P = 0.011) and those with good portal blood flow on pre-attenuation (P = 0.004) and post-attenuation (P = 0.015) portovenography. Serum interleukin (IL)-6 concentration was measured using a canine specific ELISA and significantly increased 24 h following CPSS attenuation (P < 0.001). Portal LPS was increased in dogs with CPSS, consistent with decreased hepatic clearance. TLR4 mRNA expression was significantly associated with portal blood flow and increased following surgery. These findings support the concept that portal LPS delivery is important in the hepatic response to surgical attenuation. Serum IL-6 significantly increased following surgery, consistent with LPS stimulation via TLR4, although this increase might be non-specific."

Prevalence of pancreatic, hepatic and renal microscopic lesions in post-mortem samples from Cavalier King Charles Spaniels. Kent, Andrew C. C.; Constantino-Casas, Fernando; Rusbridge, Clare; Corcoran, Brendan; Carter, Margaret; Ledger, Tania; Watson, Penny J. J. Small Animal Practice, January 2016. Quote: "Objectives: To describe the prevalence of pancreatic, hepatic and renal microscopic lesions in post-mortem samples from Cavalier King Charles Spaniels (CKCS) presented to a UK post-mortem collection scheme. Methods: Histopathology was performed on the organs of interest and the prevalence of microscopic lesions described, this was related back to the clinical signs shown ante-mortem. Results: Evidence of chronic pancreatitis was seen in 51.9% of the cases, and age correlated with severity of disease, suggesting that chronic pancreatitis is a progressive condition. Evidence of renal lesions was present in 52.2% of cases, most commonly inflammatory disease. The rate of ante-mortem diagnosis was low for both pancreatic and renal disease, at 25% and 16.7% respectively. Primary hepatic lesions were present in only 11.1% of cases, but secondary hepatic lesions were more common and were present in 64.8%. Clinical Significance: Pancreatic and renal lesions are common in Cavalier King Charles Spaniels and clinicians should be aware of this when presented with clinical cases, they have similar rates of hepatic disease as the general population."

Morphology of splenocaval congenital portosystemic shunts in dogs and cats. R. N. White, A. T. Parry. J.S.A.P. January 2016;57(1):28-32. Quote: "Objective: To describe the anatomy of congenital portosystemic shunts involving the splenic vein communicating with the caudal vena cava at the level of the epiploic foramen. Materials and Methods: A retrospective review of a consecutive series of dogs and cats managed for congenital portosystemic shunts. Results: Ninety-eight dogs and eight cats met the inclusion criteria of a congenital portosystemic shunt involving the splenic vein communicating with the prehepatic caudal vena cava plus recorded intra-operative mesenteric portovenography or computed tomography angiography and gross observations at surgery. All cases (both dogs and cats) had a highly consistent shunt that involved a distended gastrosplenic vein that communicated with the caudal vena cava at the level of the epiploic foramen via an anomalous left gastric vein. Clinical Significance: The morphology of the shunt type described appeared to be a result of an abnormal communication between the left gastric vein and the caudal vena cava and the subsequent development of preferential blood flow through an essentially normal portal venous system. The abnormal communication (shunt) was through the left gastric vein and not the splenic vein, as might have been expected. This information may help with surgical planning in cases undergoing shunt closure surgery."

Intrahepatic congenital portosystemic shunts in dogs: short- and long-term outcome of suture attenuation. M. S. Tivers, V. J. Lipscomb, P. Bristow, D. J. Brockman. J. Sm. Anim. Pract. November 2017. DOI: 10.1111/jsap.12788. Quote: Objectives: To report the short- and long-term outcomes of one- or two-staged suture attenuation for complete closure of intrahepatic congenital portosystemic shunts in dogs. Materials and Methods: Retrospective cohort study of dogs surgically treated for intrahepatic congenital portosystemic shunts between February 2000 and March 2015. Long-term follow-up was conducted by telephone conversations with the referring veterinary surgeon, owner, or both. Results: In total, 55 dogs [including 2 cavalier King Charles spaniels] had suture attenuation of their intrahepatic congenital portosystemic shunt; 10 dogs (18·2%) tolerated complete attenuation, whilst 45 dogs (81·8%) tolerated partial attenuation. Postoperative complications occurred in 24 dogs [including one CKCS] (43·6%), and six dogs (10·9%) died. Repeat surgery was performed in 33 of 39 dogs [including one CKCS] (84·6%) that had previously undergone partial attenuation, and 27 [including one CKCS] of these (84·9%) ultimately achieved complete shunt attenuation. One dog (3·0%) died following second surgery, resulting in an overall postoperative mortality of seven of 55 (12·7%). Detailed follow-up was available for 22 dogs that were still alive at a median of 29 months after surgery (7·4 to 103·1) with a subjectively good quality of life. Of 17 dogs (82·4%), 14 with complete attenuation in one or two surgeries had an excellent outcome compared with one of five dogs (20%) with persistent shunting. Clinical Significance: Staged suture ligation resulted in a high proportion of complete attenuation and reduced persistent shunting compared with a single surgery. Repeat surgery was associated with fewer complications than the first surgery. The proportion of dogs with an excellent outcome was greater for those that had complete attenuation in one or two surgeries compared with those with persistent shunting.

Clinical relevance of radiographic linear branching mineral opacities in the canine liver. M.-A. Genain, A. Barbosa, M. Herrtage, P. Watson. J. Sm. Anim. Pract. December 2017. DOI: 10.1111/jsap.12797. Quote: Various conditions have been reported to cause mineral opacities within the liver or biliary system in dogs, including parenchymal mineralisation or linear branching mineralisation. Hepatic parenchymal mineral opacification has been described in different patterns: a densely mineralised lesion, a curvilinear ring of calcification or large centrally located coarse mineralisation pattern or multiple or solitary foci of mineralisation located eccentrically within a complex heterogeneous mass. ... Branching mineralisation within the hepatic parenchyma of the dog has been reported occasionally in older small breed dogs and is the focus of this study. ... Objectives: To assess the prevalence, clinical significance and breed distribution of linear branching mineralisation superimposed on the hepatic radiographic silhouette in dogs. Materials and Methods: Retrospective review of radiographs or ultrasound images of dogs showing branching mineralisation in the liver. Results: Over the 30-year review period, 17 cases were identified and the mineralisation had a predominantly ventral distribution. Seven of the 17 were cavalier King Charles spaniels, and four of the total 17 dogs were diagnosed with hepatobiliary system disease. Five dogs had repeat radiographs, of which four showed no change in the pattern and one developed the pattern 6 years after being diagnosed with cholangiohepatitis. Serum calcium concentrations were normal in all patients. Liver enzymes were markedly elevated only in the dog diagnosed with cholangiohepatitis. Histology performed on three patients showed no convincing evidence of primary liver disease. Clinical Significance: ... Hepatic linear branching mineralisation is uncommon in dogs. CKCS appear to have an increased prevalence compared with other breeds or crossbreed dogs. Biopsy of the liver of affected dogs with no clinical or clinicopathological evidence of liver disease is unlikely to be helpful in these cases.

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