Atypical Acquired Portosystemic Shunts in a Havanese Dog with
Congenital Hepatic Diseases with Portal Hypertension
Dong-Woo Jin
Clinical Advisor: James Flanders, DVM, DACVS
Basic Science Advisor: Paul Maza, DVM, Ph. D
Senior Seminar Paper
Cornell University College of Veterinary Medicine
February 26, 2014
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Abstract
A one-year old intact female Havanese dog was referred to the Internal Medicine Service
at Cornell University Hospital for Animals (CUHA) for evaluation of portovascular anomalies
(PSVA). The patient was non-clinical for PSVA, but her pre-anesthetic bloodwork was
consistent with PSVA. On presentation to CUHA, the patient was bright, alert and responsive
with normal general physical examination. Transcolonic nuclear scintigraphy and Computed
Tomography with angiography were performed to diagnose portosystemic shunt. An exploratory
laparotomy was performed to confirm multiple, acquired extrahepatic shunts secondary to portal
hypertension. An ovariohysterectomy was performed after ensuring that the anomalous vessels
were not associated with the reproductive tract. Surgical biopsies of the liver and small intestine
were performed for histopathology which confirmed noncirrhotic portal hypertension and
inflammatory bowel disease. Post-operative management entailed medical management for the
hepatic and intestinal diseases with frequent visits to the primary care veterinarian and
monitoring of alanine aminotransferase.
History and Clinical Findings
A one-year old intact female Havanese dog was presented to the Internal Medicine
Service at CUHA in March, 2013. Earlier in the same year, the patient was presented to the
primary care veterinarian for an ovariohysterectomy. The patient had not been showing any
concerning clinical signs at home other than occasional vomiting. Her medical history included
parvoviral enteritis when she was 3 months old. The pre-anesthetic chemistry panel revealed
mildly elevated alanine aminotransferase (ALT) at 478 mg/dL (reference interval: 12-116) and
decreased blood urea nitrogen (BUN) at 4 mg/dL (reference interval: 6-31). In a follow-up
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appointment, a chemistry panel was repeated in addition to paired serum bile acid levels and
protein C assay. Results were as follows: mildly elevated ALT at 206 mg/dL (reference interval:
12-116), mildly elevated aspartate aminotransferase (AST) at 67 mg/dL (reference interval: 1566), decreased BUN at 4 mg/dL (reference interval: 6-31), mildly decreased creatinine at 0.4
mg/dL (reference interval: 0.5-1.6), mild hypocholesterolemia at 135 mg/dL (<150 considered
abnormal), markedly elevated pre-prandial bile acid level at 87.2 umol/L (<10 is normal),
markedly elevated post-prandial bile acid level at 254.8 umol/L (<20 is normal), and normal
protein C activity level at 75% (reference interval: 75-135). The urinalysis revealed magnesium
ammonium phosphate (struvite) crystals and a pH of 7.5 (reference interval: 5.5-7.0). On
presentation to the CUHA’s Internal Medicine Service, the patient was bright, alert and
responsive with a body condition score of 4/9. The general physical exam was unremarkable.
The Internal Medicine service decided not to perform more blood tests as they were performed
recently.
Problem List
The patient’s problems were chronic vomiting, increased ALT, AST, decreased BUN,
hypocholesterolemia, increased pre- and post-prandial bile acids, struvite crystalluria and
alkaliuria.
Differential Diagnoses
Differential diagnoses for chronic vomiting include, but is not exclusive to, chronic
gastritis, inflammatory bowel disease, pancreatitis, peritonitis, congenital structural abnormalities
such as a persistent right aortic arch, hepatic diseases or insufficiency, foreign objects,
intussusception, hypoadrenocorticism, diabetic ketoacidosis, uremia, and obstructive neoplasia.2
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Elevated liver enzymes can be caused by hypoxia, portosystemic vascular anomalies
(PSVA), diabetes mellitus, neoplasia, leptospirosis, histoplasmosis, chronic hepatitis, cirrhosis,
drugs (glucocorticoid, non-steroidal anti-inflammatory drugs, and tetracycline) and trauma.3
Increased bile acids can be caused by PSVA, a reduction in the functional hepatic mass,
obstructive cholestasis (hepatic or post-hepatic) and functional cholestasis.3
Differential diagnoses for hypocholesterolemia include PSVA, protein-losing
enteropathy, and hypoadrenocorticism.3
The protein C activity was within the reference interval but it was at the very low end of
the reference interval. Protein C is a vitamin-K dependent anti-coagulant that is produced by the
liver. The protein C activity level is useful in discerning different types of PSVA such as
portosystemic shunts (PSS) and microvascular dysplasia (MVD). Decreased protein C can be
caused by PSS and severe hepatic failure. 7
Struvite crystalluria develops commonly in alkalotic urine. Alkalinuria can be cause by
urinary tract infection from urease-containing bacteria, respiratory alkalosis, and proximal or
distal renal tubular acidosis.3
Ancillary Diagnostics
PSS was definitively diagnosed with transcolonic nuclear scintigraphy in this patient.
This was followed up with Computed Tomography with Angiography (CTA) to better
characterize the PSS as it is the gold standard diagnostic test for the surgical planning of PSS.1
The CTA showed a single, extrahepatic, tortuous vessel coursing near the left kidney. This
vessel seemed to be associated with the left renal vein, left ovarian vein and splenic vein. This
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vessel was not at the typical anatomic location of a single, extrahepatic PSS. While the CTA
was useful in localizing the anomalous vessel, this patient’s PSS could not be classified
definitively.
An exploratory laparotomy was performed for a visual examination of the PSS, which
revealed multiple, extrahepatic, tortuous vessels that dived into the left renal capsule. The renal
capsule was dissected away to reveal the extent of the vessels and to confirm that they were not
connected to any major veins. The shunts were not associated with the left renal, left ovarian,
splenic veins, nor the ovarian pedicle. The portal pressure was measured with a manometer
connected to a jejunal catheter to confirm a portal hypertension as the primary reason for the
PSS. The portal pressure was 9.2 cmH2O immediately after the catheterization (reference
interval: 8.13 ± 2.71) but it rose to 14-15 cmH2O when most of the larger shunts were occluded
temporarily. Portography was also performed with a portable fluoroscopic machine (C-Arm)
through the jejunal catheter to confirm the multiple shunts. The portogram also confirmed the
absence of intrahepatic shunts. The results of these ancillary tests were consistent with acquired,
multiple, extrahepatic PSS from portal hypertension. The shunts were not ligated as it would
have been extremely difficult to ligate all of the small vessels, and ligation of these vessels
would elicit resurgence of the portal hypertension and development of more shunts in the future.
An ovariohysterectomy was performed after we confirmed that the abnormal vessels were not
associated with the ovarian pedicle.
A sterile urine sample was submitted for urine culture and it was negative for urinary
tract infection.
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Histopathology
The histology of the liver showed small hepatocytes and miniaturization of the portal
triads. These lesions were consistent with primary intrahepatic portal vein hypoplasia or portal
hypoperfusion from the PSS. Histologically, the two conditions cannot be differentiated from
each other but we had a very high suspicion of congenital primary portal vein hypoplasia in this
patient because of the signalment and the early development of acquired shunts. Also, there
were increased biliary profiles within the portal triads and fibrosis along the bile ducts. These
lesions were consistent with ductal plate malformation resulting in congenital hepatic fibrosis
and intrahepatic biliary hyperplasia.9 There was moderate neutrophilic and lymphocytic
inflammation of the liver. The dog was also diagnosed with inflammatory bowel disease (IBD)
based on the lymphoplasmacytic and eosinophilic infiltration of duodenum and ileum. The
inflammation in the liver was assumed to be secondary to IBD.
Treatment
This patient was started on a medical management for the PSS before a histologic
diagnosis of IBD. The initial regimen was comprised of Hill’s L/D, metronidazole and lactulose.
Lactulose was discontinued as this patient developed vomiting and diarrhea. The regimen was
modified to a hypoallergenic diet (Royal Canin HA), Metronidazole, Vitamin E, Sadenosylmethionine and polyunsaturated phosphatidylcholine (a synthetic Silibinin) after the
diagnosis of primary portal vein hypoplasia, ductal plate malformation, and IBD.
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Follow-up
A recent communication with the owners and primary care veterinarian of this patient
revealed that the owners were not very strict with the diet regimen. The patient’s ALT increased
to 980 mg/dL and it was attributed to possible worsening of the IBD from dietary indiscretion
causing inflammation in the liver. The owners were instructed to feed the patient the
hypoallergenic diet and treats only. The patient was scheduled for an appointment with the
primary care veterinarian to monitor the liver enzymes in a month after the strict diet restriction.
The patient is doing well at home otherwise without any significant clinical signs of PSS or IBD.
Discussion
Portovascular anomalies (PSVA) can be categorized into three different classes based on
the etiology of the diseases. Congenital PSS is the most common type of PSVA.1 An abnormal
patency of fetal hepatic vessel results in a congenital PSS that connects the enteric, splenic or
pancreatic drainage directly into the venous system. The congenital PSS can be either
intrahepatic or extrahepatic, depending on which vessel retains its patency. Primary portal vein
hypoplasia is another category of PSVA that can produce similar clinicopathologic changes as in
an animal with PSS. Primary portal vein hypoplasia can result in portal hypertension, leading to
acquired PSS. Primary portal vein hypoplasia with portal hypertension is termed as congenital
noncirrhotic portal hypertension (NCPH). Primary intrahepatic portal vein hypoplasia without
portal hypertension is also known as microvascular dysplasia (MVD). MVD can be
differentiated from a true PSS by utilizing bile acid levels and protein C activity levels.
Increased liver enzymes and bile acids with decreased protein C activity are more specific for
severe hepatic failure and PSS. If the protein C activity is normal and liver enzymes and bile
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acids are increased, that is more consistent with MVD when other hepatic diseases are ruled out.7
The third category of PSVA is a disturbance in the outflow of portal (pre-hepatic) or hepatic
circulation (hepatic or post-hepatic) that leads to portal hypertension. Disturbances to the portal
circulation outflow can be from congenital, extrahepatic portal vein atresia and thrombosis,
neoplasia, stenosis, granuloma, abscess or lymphadenopathy that causes obstruction of the portal
vein. Disturbances to the hepatic circulation outflow can occur with hepatic causes such as
cirrhosis, chronic hepatitis, chronic cholangiohepatitis, ductal plate malformation (congenital
hepatic fibrosis) and lobular dissecting hepatitis. The hepatic outflow can be also disturbed from
post-hepatic causes such as right heart failure, vena cava syndrome, thrombosis, neoplasia or
trauma that causes obstruction of the hepatic vein or caudal vena cava.6
This patient was presumptively diagnosed with noncirrhotic portal hypertension (NCPH)
and ductal plate malformation based on the signalment, acquired PSS, portal hypertension and
histologic lesions. In humans, NCPH indicates a relatively non-progressive hepatobiliary
disease. The diagnosis is made after the confirmation of acquired PSS, absence of extrahepatic
portal vein obstruction, absence of post-hepatic causes of portal hypertension and observation of
characteristic histologic changes such as absent or smaller portal and central veins without signs
of cirrhosis.5 The histopathology of this patient showed fibrotic lesions, but it was more
consistent with ductal plate malformation because the bile ducts were proliferated and fibrotic
changes were evident along the bile ducts. Therefore, this patient was suspected to have NCPH
and ductal plate malformation that can both contribute to the portal hypertension.
The treatment for this patient was tailored to treat both the hepatic and intestinal diseases.
The diet was changed to a hypoallergenic diet (Royal Canin HA) instead of a low protein, liverfriendly diet such as Hill’s L/D for IBD. The patient did not show any signs of PSS at the time
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and it was decided that it was more important to control the inflammation of the intestines in
hopes of reducing the inflammatory burden on the liver. Metronidazole was used to control the
urease-producing organisms in colon and reduce the overall bowel flora that produce toxic
substances that are processed by the liver in normal animals; it also has anti-inflammatory
property in colon and useful in treating IBD. Antifibrotic therapy was started after the
confirmation of congenital hepatic fibrosis. There are many agents with antifibrotic effects such
as colchicines, polyunsaturated phosphatidylcholine (PPC), angiotensin converting enzyme
inhibitors, anti-oxidants (vitamin E, S-adenosylmethionine, silibinin, zinc), Ursodeoxycholic
acid, d-Penicillamine and other anti-inflammatory or immunomodulatory drugs. For this patient,
an antifibrotic, hepatoprotective therapy was instituted with vitamin E, S-adenosylmethionine
and PPC. Vitamin E inhibits protein kinase C activity and reduces transcription of collagen
genes as an anti-inflammatory/anti-fibrotic agent. Vitamin E is also an anti-oxidant and useful in
almost every hepatic disease as oxidative injury is a major component of nearly all hepatobillary
diseases.4 S-adenosylmethionine (SAMe) is supplemented because the availability of SAMe is
reduced in most of the hepatic diseases. SAMe is required in normal hepatic function such as
trans-methylation, trans-sulfuration and amino-propylation pathways.4 Similar to vitamin E,
PPC is an anti-inflammatory and anti-oxidative agent. Additionally, it reduces the activity of
hepatic stellate (Ito) cells that respond to profibrogenic stimuli and helps in preventing hepatic
fibrosis. It will not overturn the congenital hepatic fibrosis but it will protect the patient from
having more fibrosis, especially with the inflammation originating from IBD. PPC can also
reduce the daily dose of SAMe because the utilization of SAMe for synthesis of
phosphatidylcholine can be spared when PPC is supplemented.4
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This patient did not show any significant clinical signs of PSS and IBD such as hepatic
encephalopathy, coagulopathies or stunted growth when presented to the primary care
veterinarian or to CUHA. If left untreated, it is highly likely that this animal would have
developed such signs at some point of its life. The intention of current therapy is to control the
inflammation in the bowel and delay the progression of PSS. If the levels of liver enzymes
continue to increase, the next step is to initiate an immunomodulatory therapy.
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