Definition

• MVD describes intrahepatic microscopic vascular malformations diminishing hepatic perfusion in tertiary branches of the portal vein; this is accommodated by the compensatory increase in hepatic arterial perfusion; MVD lacks macroscopic portosystemic shunting but genetically associates with congenital portosystemic vascular anomalies (PSVA, shunts) as a component of a complex polygenic autosomal syndrome.
• Occurs as an isolated malformation or in association with PSVA.
• Clinically distinct from intrahepatic portal vein atresia that associates with numerous acquired portosystemic shunts (APSS).
• Histologic features-overlap with any condition impairing hepatopetal portal circulation (forward flow of splanchnic blood toward the liver).
• Clinicopathologic hallmark-increased total serum bile acid (TSBA) concentrations.
• Coexistence of MVD with PSVA explains: (1) failure of TSBA to normalize after complete PSVA occlusion (some dogs); and (2) inability to fully attenuate PSVA (some dogs).
• MVD diagnosis is confused by inappropriate terminology where “portal hypoplasia” has been proposed to describe features of portal venous hypoperfusion. “Hypoplasia” defines lack of development-impossible to ascertain from liver biopsy without clinical features and vascular imaging details; MVD is one of many causes of portal venous hypoperfusion.

Pathophysiology

• Malformations impairing intrahepatic portal venous perfusion deprive hepatocytes of splanchnic hepatotrophic factors-causing lobular atrophy and impairing rapid extraction of bile acids from the enterohepatic circulation.
• Compensatory increase in hepatic arterial perfusion (hepatic arterial buffer response) maintains liver viability.
• Absence of macroscopic portosystemic shunting directly into the systemic circulation explains the lack of clinical signs and hepatic encephalopathy (HE) in dogs with MVD.
• Finding signs consistent with HE in a dog thought to have MVD strongly indicates PSVA or APSS; in a young dog APSS develop with portal venous atresia, ductal plate malformation (DPM, with congenital hepatic fibrosis [CHF] phenotype), NCPH, or splanchnic portal venous thromboembolism (TE).

Systems Affected

• Usually asymptomatic.
• May observe slow recovery from injectable anesthetics and apparent adverse drug reactions with medications undergoing first-pass hepatic extraction or hepatic metabolism.
• If concurrent IBD-vomiting, diarrhea, inappetence, increased liver enzymes; may lead to centrilobular and/or portal tract inflammation; most severe in eosinophilic IBD.
• No HE in MVD-if HE identified, suspect PSVA or disorders causing APSS.
• Renal/Urologic-MVD dogs DO NOT develop ammonium biurate crystalluria/urolithiasis; if such is discovered, consider mistaken MVD diagnosis in a dog with PSVA, APSS, rare inborn errors of ammonia detoxification, or uric acid membrane transporter mutations (bulldogs, Black Russian terriers, Dalmatians, some cats).

Genetics

• Compelling evidence supports inheritance of PSVA/MVD as a complex polygenic autosomal trait in many small pure-breed dogs.
• TSBA >25 µM/L designates phenotype (affected/not affected) PSVA/MVD trait, Cornell University).
• Unaffected parents may produce affected progeny due to suspected polygenic inheritance.

Incidence/Prevalence

• Prevalence PSVA/MVD trait in small pure-breed dogs:30–80%, varies with breed.
• Genetic association of MVD and PSVA in kindreds of certain breeds confirms that MVD is most common: 10–30:1 MVD:PSVA.

Geographic Distribution

Worldwide

Signalment

Signs

Causes

Congenital inherited disorder

Risk Factors

Pure-bred small dog breeds and mixes of these breeds.

Differential Diagnosis

• PSVA-suspected in symptomatic young dog with increased TSBA or HE; however, 20% of PSVA dogs are asymptomatic.
• Symptomatic dogs >2 years of age-may have APSS caused by inflammatory, infiltrative, neoplastic, or toxic hepatopathies; DPM with CHF phenotype; rare PSVA dogs show late-onset signs (e.g., miniature schnauzers; dogs with portoazygous shunts) reflecting small relative shunt fraction; portal vein atresia (true intrahepatic portal hypoplasia) and NCPH (acquired loss of tertiary branches of the intrahepatic portal vein) associate with portal hypertension, ascites, and APSS.
• Histopathologic features of all disorders causing portal hypoperfusion are similar.

CBC/Biochemistry/Urinalysis

• CBC-normal.
• Biochemistry-generally unremarkable; hepatic enzyme activities normal (expect high ALP in young patients due to bone growth) or cyclically increased (ALT) if coexistent IBD or degenerative/inflammatory centrilobular lesions; mild hypoglobulinemia or hypoalbuminemia noted in ∼50% of young dogs.
• Urinalysis-specific gravity within normal range, no ammonium biurate crystalluria.
• Hyperammonemia is not documented dogs with MVD, without portal atresia or PSVA.

Other Laboratory Tests

Imaging

• Abdominal Radiography-lack microhepatia and renomegaly observed in PSVA.
• Abdominal Ultrasonography-no macroscopic shunting vessel; liver size subjectively normal or “slightly” small; experienced operator may suspect portal hypoperfusion that may vary among lobes.
• Mesenteric Portovenography-subtle abnormalities of blunted small portal vein branches, protracted contrast “blush” due to truncation of tertiary portal branches that trap contrast. Caution: PSVA may be overlooked if radiographic portography only completed in a single recumbent posture.
• Colorectal or Splenoportal Scintigraphy-normal or slightly increased shunt fraction in MVD; rules out macroscopic shunt (PSVA, APSS); CRS may demonstrate irregular liver lobe perfusion in MVD.

Diagnostic Procedures

• Liver biopsy-sample several liver lobes as MVD does not uniformly affect all liver lobes; AVOID SAMPLING caudate lobe as this receives perfusion from the first portal vein branch; is often the best perfused liver lobe.
• Histologic Evaluation-required for definitive diagnosis of portal hypoperfusion but must be considered in context of clinical, clinicopathologic, and imaging details; rules out most acquired hepatobiliary disorders causing increased TSBA except portal TE and NCPH.
• US-Guided Needle Biopsies-may not sample enough tissue for definitive diagnosis; limits sampling to 1 or 2 left-sided liver lobes.
• Surgical Wedge or Laparoscopic Liver Biopsies-reliably diagnostic if biopsies of several lobes obtained.

Pathologic Findings

Appropriate Health Care

• Asymptomatic-requires no medical interventions except avoidance of drugs dependent on hepatic first-pass extraction, conjugation, metabolism.
• DO NOT NEED: ursodeoxycholic acid, S-adenosylmethionine (SAMe, unless chronically increased liver enzymes), silibinin (milk thistle) or dietary protein restriction.
• Suspected HE and/or protracted vomiting or diarrhea-hospitalize for supportive care and diagnostic evaluations; these dogs have other disorders that may complicate MVD (see Hepatic Encephalopathy, Portosystemic Vascular Anomaly, Congenital, Inflammatory Bowel Disease, “Pathophysiology”).
• Rarely, dogs with zone 3 degenerative changes develop a chronic progressive hepatopathy: leads to hepatic dysfunction, portal hypertension, and ascites; diagnosis requires hepatic imaging and liver biopsy; may require management for hepatic insufficiency and ascites; more common in Maltese, Shih Tzu, Bichon Frise., Yorkshire terriers.
• Confirmed MVD associated with nonsuppurative zone 3 inflammation (especially involving eosinophils) and IBD: usually managed with low-dose dexamethasone (0.05 mg/kg PO q48–72h, rather than prednisone to avoid mineralocorticoid supplementation which may provoke ascites), hypoallergenic diet (protein restriction if HE) or a hydrolyzed protein diet, and low dose metronidazole: 7.5 mg/kg PO q12h; if low protein C: add mini-dose aspirin 0.5 mg/kg PO q12–24h or clopidogrel. Must have liver biopsy to confirm need for glucocorticoid and anticoagulants.

Nursing Care

N/A

Activity

N/A

Diet

• Dogs with MVD do not require a protein-restricted diet.
• Dogs with HE do not have simple MVD; these have complicated illnesses or PSVA-see Hepatic Encephalopathy and Portosystemic Vascular Anomaly, Congenital, and “Pathophysiology”).

Client Education

• MVD cannot be culled from a kindred based on TSBA testing; parents with normal TSBA may produce progeny with MVD or PSVA; examination of TSBA in F1 and F2 progeny is the only method of defining optimal breeding strategy, at present.
• Counsel clients that TSBA values cannot be used to grade severity of MVD.
• TSBA testing should be used to identify MVD in juvenile dogs to avoid future diagnostic confusion: e.g., adult with non-hepatic illnesses.
• Protein C-should not be used as a screening test without TSBA. Asymptomatic PSVA may have normal protein C. TSBA are ALWAYS abnormal in PSVA unless testing is inadequate (lack of provocative tolerance test, or compromised enteric fat absorption).

Surgical Considerations

N/A

Drug(s) Of Choice

For HE-see Hepatic Encephalopathy

Contraindications

N/A

Precautions

Beware of rare adverse reactions to drugs reliant on hepatic first-pass extraction or metabolism.

Possible Interactions

N/A

Alternative Drug(s)

N/A

Patient Monitoring

• Asymptomatic dogs-no specific treatment/long-term follow-up has confirmed normal lifespan, no chronic illness, no progressive hepatic degeneration.
• Repeated TSBA tests are not advised as values remain abnormal and fluctuate due to physiologic variables that clients find difficult to understand.

Prevention/Avoidance

Specific recommendations to eliminate MVD from a particular genetic line or breed are not possible at present. Based on information derived from large pedigrees of multiple dog breeds, simply breeding unaffected parents does not eliminate MVD from a kindred. In high-incidence kindreds remain vigilant for vaguely ill dogs that may have PSVA; surgical exploration can miss PSVA as can portovenography if only a single recumbency is evaluated); CRS can definitively detect hepatofugal blood flow (portosystemic shunting) providing a quick YES/NO test for portosystemic shunting; protein C activity assists in differentiating dogs with PSVA from MVD to advise further expensive imaging but is not definitive as a stand-alone test.

Possible Complications

N/A

Expected Course and Prognosis

• Most dogs with MVD remain asymptomatic and have a normal lifespan.
• Progressive increase in magnitude of TSBA values with age (juvenile to adult) has been documented in MVD.
• Generally, TSBA tests in MVD dogs are not quantitatively related to histologic severity.
• Dogs with zone 3 degenerative lesions (described above) may develop progressive hepatopathy leading to HE, portal hypertension, APSS, ascites, and rarely portal venous thromboembolism; this is a rare syndrome.

Associated Conditions

Small-breed dogs with high incidence of PSVA affected.

Age-Related Factors

TSBA can be used to screen young dogs (16 weeks of age) in breeds known to have high prevalence of PSVA/MVD.

Zoonotic Potential

N/A

Pregnancy/Fertility/Breeding

Bitches with MVD carry litters to term.

Synonyms

• Congenital portal hypoperfusion
• Hepatic microvascular dysplasia
• Microscopic portovascular dysplasia

Confused Terminology

• Intrahepatic portal venous atresia is not a synonym for MVD
• Portal venous hypoplasia is not a synonym for MVD

See Also

• Ductal Plate Malformation (Congenital Hepatic Fibrosis)
• Hepatic Encephalopathy
• Portosystemic Vascular Anomaly, Congenital
• Portosystemic Shunting, Acquired

Abbreviations

• ALP = alkaline phosphatase
• ALT = alanine aminotransferase
• AST = aspartate aminotransferase
• APSS = acquired portosystemic shunt
• CRS = colorectal scintigraphy
• ICG = indocyanine green
• MVD = microvascular dysplasia
• NCPH = non-cirrhotic portal hypertension
• PSS = portosystemic shunting
• PSVA = portosystemic vascular anomaly
• SPS = splenoportal scintigraphy
• TE = thromboembolism
• TSBA = total serum bile acids