Bertie, a 7 year old male neutered Domestic Shorthair cat

Clinical history

Bertie presented with chronic vomiting, intermittently reduced appetite and weight loss. Liver enzymes were increased and the liver had an abnormal appearance on ultrasound.

Histology

Histologically, the normal hepatic tissue architecture was disturbed by moderate to marked expansion of portal tracts, which were often bridging. The expansion was caused by increased amounts of fibrous connective tissue, embedded in which were numerous small bile ducts. These were often tortuous with narrow lumina. Often, multiple cross sections through small arterioles were present, while distinct portal vein profiles were often lacking. Some portal areas were moderately infiltrated with small lymphocytes admixed with lower numbers of plasma cells; occasionally, small numbers of neutrophils were observed.

Figure 1: Bridging fibrosis between portal tracts.

Figure 2: Numerous tortuous bile ducts (examples: blue arrow heads) are embedded in fibrous connective tissue expanding the portal tract; red arrow head: arteriolar profile; mild mixed inflammation.

Interpretation

Consistent with congenital hepatic fibrosis

Note, that while in this case the histopathological findings are diagnostic, in some cases this condition can be difficult to differentiate from chronic cholangitis with reactive biliary proliferation. However, significant hepatic fibrosis other than associated with congenital hepatic fibrosis is rare in cats, therefore, if significant fibrosis is observed, congenital hepatic fibrosis should always be a consideration.

What is Congenital Hepatic Fibrosis?

Congenital hepatic fibrosis (CHF) is a form of ductal plate malformation, which is described in humans and several animal species including cats, dogs, horses, calves, rats and non-human primates.

In cats, CHF is often associated with autosomal dominant polycystic kidney disease due to a mutation in the PKD1 gene, in particular in Persian or Persian mix cats. Between 22-48% of cats with feline PKD are reported to also have CHF. However, hepatic lesions can also occur without lesions in the kidney. Apart from CHF type lesions, multiple larger hepatic cysts can also occur.

Feline CHF is often clinically silent in cats until later in life, when presumably the progressive fibrosis causes altered liver function. Feline CHF is only rarely associated with portal hypertension and acquired portosystemic shunting.

Some tips and tricks on sampling liver for histopathology

The histopathological diagnostic of hepatic disease requires in most cases an assessment of the hepatic tissue architecture – is it normal or abnormal? If the architecture is abnormal, then which elements are affected and how? It was therefore proposed that a minimum of 12-15 portal tracts is required for a reliable assessment. This is best achieved with guillotine wedge or laparoscopic liver biopsies. However, these sampling methods are more invasive than Tru-cut (needle) biopsies. Determination of the biopsy type (Tru-cut, laparoscopic, guillotine wedge) requires assessment of the patient’s coagulation parameters, distribution of the liver lesions on ultrasound, and the available tools. For Tru-cut needle biopsies, diagnostic accuracy is increased with a larger gauge needle (14 or 16) and by obtaining biopsies from multiple sites.  To keep your Tru-cut biopsies safe from breaking apart during transport, we would highly recommend use of a histology cassette, which is then submerged in formalin. Please do not use sponges in the cassettes with fresh tissue, as this will cause artefact. Make sure all air in the cassette has been replaced by formalin for optimal fixation.

We can provide histology cassettes on request.

Figure 3: Examples of histology cassettes for biopsy protection.

References

Guerra JM, Daniel AGT, Cardoso NC, Grandi F, Quieroga F, Cogliati B. Congenital hepatic fibrosis and polycystic kidney disease not linked to C>A mutation in exon 29 of PKD1 in a Persian cat. J Fel Med Surg Open Rep 2015; doi: 10,1177, 2055116915619191

Webster et al. ACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs. 2019;33:1173-1200

Zandvliet MM, Szatmari V, van den lngh T, Rothuizen J. Acquired portosystemic shunting in 2 cats secondary to congenital hepatic fibrosis. Journal of Veterinary Internal Medicine. 2005;19(5),765-767.