NONCIRRHOTIC PORTAL-HYPERTENSION AND NODULAR REGENERATIVE HYPERPLASIAOF THE LIVER IN DOGS WITH MUCOPOLYSACCHARIDOSIS TYPE-I

Nodular regenerative hyperplasia (NRH) is an uncommon hepatic lesion o ften associated with noncirrhotic portal hypertension (PI-IT). We have noted that NRH and PI-IT are frequent occurrences in a colony of dogs with the genetic storage disease, mucopolysaccharidosis I (MPS-I). Th is observation provides the opportunity to study the histology and pat hogenesis of NRH and noncirrhotic PHT in a new animal model. Thirteen of 32 dogs (41%) with MPS-I developed multiple portocaval shunts betwe en 4 and 48 months of age that were grossly visible at necropsy Seven of the 13 developed marked ascites, whereas all those without shunts a nd littermates (n = 24) heterozygous for the mutated alpha-L-iduronida se allele (carriers unaffected by the storage disease) did not. The la rge and medium-sized portal veins were widely patent without thrombosi s or vascular malformations. Hepatic parenchymal fibrosis was absent o r mild and did not correlate with shunt formation. All 32 livers had v arying degrees of diffuse periportal hepatocellular hyperplasia with m ultifocal atrophy and compression of centrolobular cords (NRH) most pr ominent in dogs with shunts. Many small portal veins were reduced in d iameter or absent, especially in animals with shunts. Noncirrhotic PHT and NRH appear to be related to the obliteration of small portal vein s in these dogs, but the pathogenesis of this vascular change remains unknown.