Standardized Histological Evaluation of Primary Sclerosing Cholangitis (PSC): Relationship of Histological Features to Laboratory Findings and Outcome
David E Kleiner, Elizabeth M Brunt, Keith D Lindor, Jayant A Talwalkar. National Cancer Institute, Bethesda, MD; Washington University, St. Louis, MO; Arizona State University, Phoenix, AZ; Mayo Clinic, Rochester, MN
Background: Primary sclerosing cholangitis (PSC) is a progressive, chronic cholestatic liver disease characterized by duct destruction. We developed a standardized method of histologic evaluation for PSC and related histologic findings to clinical disease parameters.
Design: Study entry liver biopsies from the PSC-Ursodiol treatment trial (n=84) (Hepatology 50: 808; 2009) were stained with H&E, trichrome, reticulin, copper and cytokeratin 7 (CK7). Blinded semiquantitative evaluation of features of duct damage, inflammation, fibrosis, cholestasis and special stains were performed independently by 2 hepatopathologists. For each portal area on the CK7 stain, presence/absence of ducts and the degree of ductular reaction (DR) was recorded. A mean DR score and fraction of portal areas with ducts (DF) was calculated. The relationship between histologic and clinical features at baseline was assessed by Spearman rank correlation Rho, Chi-square or Mann-Whitney tests as appropriate.
Results: The study cohort had a mean age of 45 years and 47 (56%) were male. Alkaline phosphatase (AlkP) correlated strongly with histologic features of cholestasis, including duct injury, pseudoxanthomatous change (PXC), copper, periportal CK7 staining, DF and DR (all p<0.001) as well as with lobular inflammation and fibrosis. AST correlated with PXC, copper, DR and fibrosis (p<0.002). The Mayo PSC Risk Score was strongly correlated with PXC, copper, periportal CK7 staining and DR (p<0.0001) as well as fibro-obliterative duct lesions (p=0.001), and fibrosis (p=0.0001). The protocol defined composite outcome (including cirrhosis, varices, carcinoma, transplantation and death) was met in 31 (37%) of these patients during the study. The development of an adverse outcome was strongly associated with DF and DR (Mann-Whitney, p<0.0001) as well as copper (p=0.0006) and PXC (p=0.001) (Chi-square).
Conclusions: In a standardized evaluation of PSC biopsies from this clinical trial, features of chronic cholestasis showed a high degree of correlation with baseline measures of AlkP and AST as well as the calculated Mayo PSC Risk Score and the protocol defined composite outcome. These observations offer promise that standardized histologic evaluation of PSC can offer insights into the unique aspects of this cholestatic disease process and s methods of evaluating histologic response to therapeutic intervention.
Monday, March 4, 2013 1:30 PM
Proffered Papers: Section E, Monday Afternoon