[1692] Altered Hepatic Vascular and Lobular Organization near Centrizonal Scars in Chronic Venous Outflow Obstruction

Gregor Krings, Bilge Meydan, Linda Ferrell. UCSF, San Francisco, CA; Ondokuz Mayis, Samsun, Turkey

Background: Chronic hepatic venous outflow obstruction (CVOO) is characterized by centrizonal (cz) hepatocyte ischemia, atrophy, necrosis, sinusoidal fibrosis and zone 3 scarring. Other conditions associated with cz scarring such as steatohepatitis often show aberrant cz arterialization and hepatocytic ductular metaplasia (DM). We have shown that cz scars in CVOO also undergo arterialization and ductular reaction (DR), which correlate with degree of fibrosis and may result in misinterpretation of CVOO as a biliary problem. However, consequences of the vascular alterations on functional lobular organization and hepatobiliary differentiation remain undefined.
Design: We studied 25 CVOO cases previously evaluated for cz arterialization, DR, and fibrosis. IHC was performed for CD34 to assess changes in cz sinusoidal staining as surrogate for vascular flow abnormalities (n=24) and for K7 and K19 to assess for DM or progenitor cell presence (n=25). Grading was semi-quantitative (scale 0-3). IHC for glutamine synthetase (GS) was performed to assess changes in normal lobular zonation (n=23). Cz fibrosis was staged using NASH criteria.
Results: Cz sinusoidal CD34 staining was present in 23 of 24(95.8%) cases; 13(54.2%) showed 2-3+ staining. Extent of staining correlated with cz microvessels (mv; p=0.001) but not cz arterialization (czA; p=1.00). CzA correlated with fibrosis stage (p=0.008); CD34 and mv did not (p=0.433 and p= 0.52). Four cases (16.7%) were CD34+ in absence of ductules with minimal (1b) fibrosis; all cases with cz ductules or stage 2-4 fibrosis were CD34+. Most cz ductules were K7+/K19-; 21 of 25(84%) cases were K7+ and 14(56%) were K19+ (p=0.025) with K19Conclusions: Cz sinusoidal CD34 staining and loss of cz GS zonation are common in CVOO. The associated cz ductules may represent DM rather than ingrowth of progenitor cells, evidenced by keratin profiling. CD34 staining may precede DM and higher fibrosis stages, further suggesting possible chronic ischemic etiology. Lastly, in addition to cz scarring, DM, and arterial ingrowth, the aberrant cz endothelialization and loss of GS zonation may further cause misinterpretation of central zones as portal tracts with resultant misdiagnosis as a biliary problem.
Category: Liver

Wednesday, March 6, 2013 1:00 PM

Poster Session VI # 115, Wednesday Afternoon


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