2006 - UZ Leuven

van de gezonde donor met een gerapporteerd mortaliteitsrisico van0,5%.KATOONIZADEH A., NEVENS F., VERSLYPE C., PIRENNE J., ROSKAMST.: Liver regeneration in acute severe liver impairment: aclinicopathological correlation study. Liver International, 2006; 26(10):1225-1233.Background: Although normally quiescent, the adult mammalian liverpossesses a great capacity to regenerate after different types ofinjury. Major players in the regeneration process are mature residualcells, including hepatocytes, cholangiocytes and stromal cells.However, if the regenerative capacity of mature cells is impaired,hepatic progenitor cells (HPCs) are activated and expand into theliver parenchyma. Upon transit amplification, the progenitor cellsgenerate new hepatocytes and biliary cells to restore liverhomeostasis.Aims/Methods: To study the relationship between differenthistopathological parameters as well as their correlations with clinicalparameters and outcome, we examined liver specimens from 74patients with acute or subacute severe liver impairment byimmunohistochemistry for CK7/CK19 (evaluation of HPCsactivation/differentiation), Mib1(Ki 67)/P21 (evaluation of proliferativeactivity/proliferation arrest of hepatocytes) and hematoxylin andeosin (evaluation of hepatocyte loss).Results: Of the 74 patients, 32% survived without transplantation,14% died without transplantation and 54% were transplanted. Ourresults show that a threshold of 50% loss of hepatocytes, associatedwith significant decrease in the proliferative activity of remainingmature hepatocytes, is needed for extensive hepatic progenitor cellactivation. Such activation is a sign of disease severity and occursearly (within 1 week) in the disease course. However, developmentof intermediate hepatocytes, suggesting HPCs differentiationtowards mature hepatocytes, takes at least 1 week's time. We founda positive correlation between histopathological parameters(percentage hepatocyte loss, number of proliferating hepatocytesand number of HPCs) and clinical parameters of liver impairmentsuch as model for end stage liver diseases (MELD). Survivingpatients compared with those who either died or were transplantedhad significantly less hepatocyte loss, less HPCs activation andmore mature hepatocyte proliferative activity. Hepatocyteproliferative activity and degree of hepatocyte loss were the mostimportant independent histopathological parameters in predictingoutcome. Conclusion: Liver biopsy can provide important additionalinformation in a patient with severe acute liver impairment.15