The Central Zone “Portalization” Phenomenon in Nonalcoholic Steatohepatitis (NASH)
Jennifer M Oliver-Krasinski, Leonore C Peruyero, Roger K Moreira. Columbia University/New York Presbyterian Hospital, New York, NY
Background: Ferrell and collegues (AASLD abstract, 2007) have reported the presence of arterialized vessels and ductular structures within fibrosed central zones (CZ) in cases of NASH. We sought to further characterize this phenomenon with the aid of glutamine synthetase (GS) – a marker of CZ hepatocytes.
Design: 46 liver biopsies from patients with NASH (M=19, F=27, mean age 48.1 [range 9-53]), stages 1a-3 were evaluated by H&E, trichrome and double GS/CK-7 and GS/SMA IHC. Special attention was given to CZ findings. Nine biopsies showing simple steatosis were used as controls.
Results: Our study has confirmed the frequent occurrence of arterioles and ductular structures in fibrotic CZs in NASH. The concomitant presence of “dense” fibrosis and inflammation may impart a distinct “portal tract-like” appearance to these CZs, which may be confused with true portal tracts on routine stains. Double staining using either CK7 or SMA with GS greatly facilitated the recognition of portalized central areas and allowed the recognition of central-portal approximation and/or fusion in most cases, indicating that parenchymal extinction and subsequent linking of portal and central spaces with ingrowth of portal structures into CZs likely represents the underlying mechanism of centrilobular "portalization" in NASH. Interestingly, migration of putative hepatic progenitor cells (HPC) (very small, strongly CK7+ cells within the hepatic lobule) into CZs was identified in all cases showing centrilobular arterioles or ductules and in some cases with earlier CZ changes. Associated features are shown in Table 1. Simple steatosis controls showed none of the above CZ abnormalities.
|CZ arteries or ductules present (n=24)||CZ arteries or ductules absent (n=22)||P value|
|NAS* (median, range)||4 (3-7)||5 (3-7)||NS|
|NAS ballooning = 2||10 (41.6%)||2 (9%)||0.01|
|Mallory bodies||22 (91.6%)||14 (63.6%)||0.02|
|Stage >1a (Kleiner & Brunt)||21 (87.5%)||13 (59%)||0.02|
|Ductular reaction||11 (45.8%)||3 (13.6%)||0.01|
|Dense CZ fibrosis||17 (70.8%)||6 (27.2%)||0.003|
|CZ chronic inflammation||16 (66.6%)||4 (18.1%)||0.0009|
|Putative HPCs in CZs||24 (100%)||12 (54.5%)||0.0002|