Congenital Hepatic Fibrosis in 5 Dogs

Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University Raleigh, NC, USA.
Veterinary Pathology (Impact Factor: 2.04). 01/2010; 47(1):102-7. DOI: 10.1177/0300985809353313
Source: PubMed

ABSTRACT Congenital hepatic fibrosis is a disorder of biliary system development histologically characterized by diffuse periportal to bridging fibrosis with numerous small often-irregular bile ducts and reduction in the number of portal vein branches. The condition results from abnormal development of the ductal plate, the embryonic precursor to the interlobular bile ducts. It has rarely been reported in veterinary species, and it has never been reported in dogs. This article describes 5 cases of a ductal plate malformation in dogs consistent with congenital hepatic fibrosis. On light microscopy, all 5 livers had severe bridging fibrosis with a marked increase in the number of small bile ducts, which often had irregular, dilated profiles reminiscent of the developing ductal plate. In addition, 80% (4 of 5) of cases lacked typical portal vein profiles. Cytokeratin 7 and proliferating cell nuclear antigen immunohistochemistry was performed on the 3 cases for which paraffin-embedded tissue was available. The bile duct profiles were strongly positive for cytokeratin 7 in all 3 cases, and they were negative for proliferating cell nuclear antigen or only had rare positive cells. All 5 dogs presented with clinical signs of portal hypertension. Congenital hepatic fibrosis should be considered in the differential diagnosis in young dogs that present with portal hypertension and lesions that may have been interpreted as bridging biliary hyperplasia or extrahepatic biliary obstruction.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Congenital hepatic fibrosis has been described as a lethal disease with monogenic autosomal recessive inheritance in the Swiss Franches-Montagnes horse breed. We performed a genome-wide association study with 5 cases and 12 controls and detected an association on chromosome 20. Subsequent homozygosity mapping defined a critical interval of 952 kb harboring 10 annotated genes and loci including the polycystic kidney and hepatic disease 1 (autosomal recessive) gene (PKHD1). PKHD1 represents an excellent functional candidate as variants in this gene were identified in human patients with autosomal recessive polycystic kidney and hepatic disease (ARPKD) as well as several mouse and rat mutants. Whereas most pathogenic PKHD1 variants lead to polycystic defects in kidney and liver, a small subset of the human ARPKD patients have only liver symptoms, similar to our horses with congenital hepatic fibrosis. The PKHD1 gene is one of the largest genes in the genome with multiple alternative transcripts that have not yet been fully characterized. We sequenced the genomes of an affected foal and 46 control horses to establish a comprehensive list of variants in the critical interval. We identified two missense variants in the PKHD1 gene which were strongly, but not perfectly associated with congenital hepatic fibrosis. We speculate that reduced penetrance and/or potential epistatic interactions with hypothetical modifier genes may explain the imperfect association of the detected PKHD1 variants. Our data thus indicate that horses with congenital hepatic fibrosis represent an interesting large animal model for the liver-restricted subtype of human ARPKD.
    PLoS ONE 10/2014; 9(10):e110125. DOI:10.1371/journal.pone.0110125 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Portal hypertension (PH) is the result of increased vascular resistance in the portal circulation, increased portal venous blood flow, or both. In veterinary medicine, where portal pressure is seldom measured directly, the diagnosis of PH often is inferred from identification of associated complications including multiple acquired portosystemic shunts, ascites, and hepatic encephalopathy. Likewise, treatment of PH primarily is aimed at controlling these complications. The goal of this review is to provide an update on the pathophysiology, diagnosis, and treatment of PH. The review draws from information in the veterinary hepatology literature, reviews, and consensus statements in human hepatology and the literature on experimental models of PH.
    Journal of Veterinary Internal Medicine 03/2011; 25(2):169-86. DOI:10.1111/j.1939-1676.2011.00691.x · 2.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A captive 3-mo-old white African lion (Panthera leo) presented with clinical signs of acute pain and a distended abdomen. Despite emergency treatment, the lion died a few hours after presentation. Postmortem examination revealed gross changes in the liver, spleen, and lungs and an anomalous cystic structure in the bile duct. Histologic examination identified severe generalized multifocal to coalescent necrotizing and neutrophilic hepatitis, neutrophilic splenitis, and mild interstitial pneumonia, consistent with bacterial septicemia. The abnormal biliary structures resembled biliary cystadenoma. However, due to the age of the animal, they were presumed to be congenital in origin. Biliary tract anomalies and cystadenomas have been reported previously in adult lions, and this case suggests that at least some of these examples may have a congenital basis. It is unclear whether the lesion was an underlying factor in the development of hepatitis.
    Journal of Zoo and Wildlife Medicine 12/2012; 43(4):922-6. DOI:10.2307/23361392 · 0.32 Impact Factor

Similar Publications