[1633] Perivenular Biliary Metaplasia of Hepatocytes and Not a Periportal Ductular Reaction Correlates with a Cholestatic Liver Chemistry Profile in Patients with Hepatic Venous Outflow Obstruction

RK Pai, J Hart. Washington University, St. Louis; Univ. of Chicago, Chicago

Background: Patients with venous outflow obstruction often have an unexpected cholestatic pattern of liver chemistry tests. Elevations in alkalaine phosphatase and bilirubin 2 to 5 times normal is not unusual. Kakar et al recently described portal changes in patients with outflow obstruction (Mod Path 2004 17:874). In this study ∼50% of patients had evidence of a bile ductular reaction. However, no patient had evidence of biliary tract disease. They argued that such changes could account for the cholestatic profile. However, it is unclear if a ductular reaction can explain the cholestatic profile in all patients with outflow obstruction.
Design: 22 needle liver biopsies from patients with congestive heart failure were analyzed histologically and immunohistochemically for CK7. Histologic parameters were degree of sinusoidal dilatation, fibrosis, ductular reaction, and portal inflammation. The patient's liver chemistry tests at the time of biopsy was recorded.
Results: We found that 32% of patients (7 of 22) had histologic evidence of mild periportal ductular reaction. A CK7 immunostain demonstrated a subtle periportal ductular reaction in two additional cases. Strikingly, the CK7 immunostain also demonstrated prominent biliary metaplasia of perivenular hepatocytes in the majority of cases (focal zone-3 in 11, diffuse zone-3 in 3, and diffuse zones-3 and -2 in 5 patients). The presence of a periportal ductular reaction did not correlate with a cholestatic liver chemistry profile (Table 1). However, the degree of sinusoidal dilatation as well as perivenular biliary metaplasia was a strong predictor of a cholestatic profile.

Correlation with cholestatic chemistry tests in patients with outflow obstruction

Category	N	Bilirubin	Alkaline Phosphatase	AST	ALT
All patients	22	2.15	169	40	39
Sinusoidal dilatation
Zone 3	7	1.54	149	64	43
Zones 2-3	8	1.83	175	31	37
Zones 1-3	6	3.33	183	27	37
Biliay metaplasia
Zone 3 (focal and diffuse)	14	1.90	169	30	40
Diffuse Zones 2-3	5	3.90	193	18	27
Ductular reaction	9	2.10	147	26	39

Conclusions: In patients with outflow obstruction there can be marked biliary metaplasia of hepatocytes in zones 2 and 3. Biliary metaplasia and sinusoidal dilatation predict a cholestatic liver chemistry profile. The etiology of the biliary metaplasia is unclear, but may represent a response to an injury to the canalicular system due to compression of the hepatic plates by impairment of blood flow.
Category: Liver & Pancreas

Monday, March 22, 2010 1:00 PM

Poster Session II # 174, Monday Afternoon